Nephrology

People who habitually add salt to their meals at the table may unknowingly be risking their kidneys, according to a study utilizing UK Biobank data. Chronic salt additions are associated with an elevated risk of developing chronic kidney disease (CKD), as revealed by researchers led by Rui Tang, a doctoral candidate in epidemiology at Tulane University in New Orleans, Louisiana. The study was published in JAMA Network Open.

Large Study Sample

In a population-based cohort study comprising over 460,000 UK Biobank participants aged 37-73 years, the researchers explored the association between adding table salt to food and increased CKD risk.

Participants indicated how often they added salt to their meals: Never or rarely, sometimes, often, or always. The follow-up period exceeded a decade, and median duration was 11.8 years. During this time, approximately 22,000 new CKD cases were documented. Data analysis revealed a significantly higher CKD risk among those who frequently added salt.

The extent of risk elevation varied with the frequency of salt additions. Even occasional salters had a 7% higher risk than those who never or rarely added salt. For frequent salters, the risk increased by 12%, and for those who always added salt, it rose to 29%. These results were adjusted for age and gender.

Worse Overall Health

The research group noted that individuals who frequently added salt were generally less healthy, adopting an unhealthier lifestyle and having lower socioeconomic status. They exhibited higher body mass index (BMI), were more likely to smoke, had diabetes or cardiovascular diseases, and had reduced estimated glomerular filtration rate (eGFR) at the beginning of the study. Moreover, their Townsend Deprivation Index, indicating material deprivation, was higher.

Considering these factors, the researchers adjusted the results not only for age and gender but also for ethnicity, Townsend Deprivation Index, eGFR, BMI, smoking status, alcohol consumption, physical activity, elevated cholesterol levels, diabetes, cardiovascular diseases, hypertension, infectious diseases, immune system disorders, and the use of nephrotoxic medications.

Association Persists

Even after accounting for these factors, a significant, albeit attenuated, association between salt additions and CKD risk remained. The risk increased by 2% for occasional salters, 5% for frequent salters, and 6% for those who always added salt.

The research group concluded that adding salt to meals could be associated with an increased risk for CKD in the general population. However, they highlighted several limitations that should be considered when interpreting the study results.

Reducing Salt 

Primarily, self-reported frequency of salt addition doesn’t precisely reflect actual salt consumption. While earlier studies validated the accuracy of this variable, the researchers acknowledged the possibility that frequent salt addition may merely be a marker for an unhealthy lifestyle.

Nevertheless, the authors speculated that reducing the frequency of salt additions to meals could contribute to lowering CKD risk in the general population. They suggested validating their results in post hoc analyses or follow-up studies from clinical trials.
 

This article was translated from the Medscape German edition. A version of this article appeared on Medscape.com.

People who habitually add salt to their meals at the table may unknowingly be risking their kidneys, according to a study utilizing UK Biobank data. Chronic salt additions are associated with an elevated risk of developing chronic kidney disease (CKD), as revealed by researchers led by Rui Tang, a doctoral candidate in epidemiology at Tulane University in New Orleans, Louisiana. The study was published in JAMA Network Open.

Large Study Sample

In a population-based cohort study comprising over 460,000 UK Biobank participants aged 37-73 years, the researchers explored the association between adding table salt to food and increased CKD risk.

Participants indicated how often they added salt to their meals: Never or rarely, sometimes, often, or always. The follow-up period exceeded a decade, and median duration was 11.8 years. During this time, approximately 22,000 new CKD cases were documented. Data analysis revealed a significantly higher CKD risk among those who frequently added salt.

The extent of risk elevation varied with the frequency of salt additions. Even occasional salters had a 7% higher risk than those who never or rarely added salt. For frequent salters, the risk increased by 12%, and for those who always added salt, it rose to 29%. These results were adjusted for age and gender.

Worse Overall Health

The research group noted that individuals who frequently added salt were generally less healthy, adopting an unhealthier lifestyle and having lower socioeconomic status. They exhibited higher body mass index (BMI), were more likely to smoke, had diabetes or cardiovascular diseases, and had reduced estimated glomerular filtration rate (eGFR) at the beginning of the study. Moreover, their Townsend Deprivation Index, indicating material deprivation, was higher.

Considering these factors, the researchers adjusted the results not only for age and gender but also for ethnicity, Townsend Deprivation Index, eGFR, BMI, smoking status, alcohol consumption, physical activity, elevated cholesterol levels, diabetes, cardiovascular diseases, hypertension, infectious diseases, immune system disorders, and the use of nephrotoxic medications.

Association Persists

Even after accounting for these factors, a significant, albeit attenuated, association between salt additions and CKD risk remained. The risk increased by 2% for occasional salters, 5% for frequent salters, and 6% for those who always added salt.

The research group concluded that adding salt to meals could be associated with an increased risk for CKD in the general population. However, they highlighted several limitations that should be considered when interpreting the study results.

Reducing Salt 

Primarily, self-reported frequency of salt addition doesn’t precisely reflect actual salt consumption. While earlier studies validated the accuracy of this variable, the researchers acknowledged the possibility that frequent salt addition may merely be a marker for an unhealthy lifestyle.

Nevertheless, the authors speculated that reducing the frequency of salt additions to meals could contribute to lowering CKD risk in the general population. They suggested validating their results in post hoc analyses or follow-up studies from clinical trials.
 

This article was translated from the Medscape German edition. A version of this article appeared on Medscape.com.

People who habitually add salt to their meals at the table may unknowingly be risking their kidneys, according to a study utilizing UK Biobank data. Chronic salt additions are associated with an elevated risk of developing chronic kidney disease (CKD), as revealed by researchers led by Rui Tang, a doctoral candidate in epidemiology at Tulane University in New Orleans, Louisiana. The study was published in JAMA Network Open.

Large Study Sample

In a population-based cohort study comprising over 460,000 UK Biobank participants aged 37-73 years, the researchers explored the association between adding table salt to food and increased CKD risk.

Participants indicated how often they added salt to their meals: Never or rarely, sometimes, often, or always. The follow-up period exceeded a decade, and median duration was 11.8 years. During this time, approximately 22,000 new CKD cases were documented. Data analysis revealed a significantly higher CKD risk among those who frequently added salt.

The extent of risk elevation varied with the frequency of salt additions. Even occasional salters had a 7% higher risk than those who never or rarely added salt. For frequent salters, the risk increased by 12%, and for those who always added salt, it rose to 29%. These results were adjusted for age and gender.

Worse Overall Health

The research group noted that individuals who frequently added salt were generally less healthy, adopting an unhealthier lifestyle and having lower socioeconomic status. They exhibited higher body mass index (BMI), were more likely to smoke, had diabetes or cardiovascular diseases, and had reduced estimated glomerular filtration rate (eGFR) at the beginning of the study. Moreover, their Townsend Deprivation Index, indicating material deprivation, was higher.

Considering these factors, the researchers adjusted the results not only for age and gender but also for ethnicity, Townsend Deprivation Index, eGFR, BMI, smoking status, alcohol consumption, physical activity, elevated cholesterol levels, diabetes, cardiovascular diseases, hypertension, infectious diseases, immune system disorders, and the use of nephrotoxic medications.

Association Persists

Even after accounting for these factors, a significant, albeit attenuated, association between salt additions and CKD risk remained. The risk increased by 2% for occasional salters, 5% for frequent salters, and 6% for those who always added salt.

The research group concluded that adding salt to meals could be associated with an increased risk for CKD in the general population. However, they highlighted several limitations that should be considered when interpreting the study results.

Reducing Salt 

Primarily, self-reported frequency of salt addition doesn’t precisely reflect actual salt consumption. While earlier studies validated the accuracy of this variable, the researchers acknowledged the possibility that frequent salt addition may merely be a marker for an unhealthy lifestyle.

Nevertheless, the authors speculated that reducing the frequency of salt additions to meals could contribute to lowering CKD risk in the general population. They suggested validating their results in post hoc analyses or follow-up studies from clinical trials.
 

This article was translated from the Medscape German edition. A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has added a boxed warning to the label of the osteoporosis drug denosumab (Prolia) about increased risk for severe hypocalcemia in patients with advanced chronic kidney disease (CKD). 

Denosumab is a monoclonal antibody, indicated for the treatment of postmenopausal women with osteoporosis who are at increased risk for fracture for whom other treatments aren’t effective or can’t be tolerated. It’s also indicated to increase bone mass in men with osteoporosis at high risk for fracture, treat glucocorticoid-induced osteoporosis in men and women at high risk for fracture, increase bone mass in men at high risk for fracture receiving androgen-deprivation therapy for nonmetastatic prostate cancer, and increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.

This new warning updates a November 2022 alert based on preliminary evidence for a “substantial risk” for hypocalcemia in patients with CKD on dialysis. 

Upon further examination of the data from two trials including more than 500,000 denosumab-treated women with CKD, the FDA concluded that severe hypocalcemia appears to be more common in those with CKD who also have mineral and bone disorder (CKD-MBD). And, for patients with advanced CKD taking denosumab, “severe hypocalcemia resulted in serious harm, including hospitalization, life-threatening events, and death.” 

Most of the severe hypocalcemia events occurred 2-10 weeks after denosumab injection, with the greatest risk during weeks 2-5.

The new warning advises healthcare professionals to assess patients’ kidney function before prescribing denosumab, and for those with advanced CKD, “consider the risk of severe hypocalcemia with Prolia in the context of other available treatments for osteoporosis.”

If the drug is still being considered for those patients for initial or continued use, calcium blood levels should be checked, and patients should be evaluated for CKD-MBD. Prior to prescribing denosumab in these patients, CKD-MBD should be properly managed, hypocalcemia corrected, and patients supplemented with calcium and activated vitamin D to decrease the risk for severe hypocalcemia and associated complications.

“Treatment with denosumab in patients with advanced CKD, including those on dialysis, and particularly patients with diagnosed CKD-MBD should involve a health care provider with expertise in the diagnosis and management of CKD-MBD,” the FDA advises. 

Once denosumab is administered, close monitoring of blood calcium levels and prompt hypocalcemia management is essential to prevent complications including seizures or arrythmias. Patients should be advised to promptly report symptoms that could be consistent with hypocalcemia, including confusion, seizures, irregular heartbeat, fainting, muscle spasms or weakness, face twitching, tingling, or numbness anywhere in the body. 

In 2022, an estimated 2.2 million Prolia prefilled syringes were sold by the manufacturer to US healthcare settings.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has added a boxed warning to the label of the osteoporosis drug denosumab (Prolia) about increased risk for severe hypocalcemia in patients with advanced chronic kidney disease (CKD). 

Denosumab is a monoclonal antibody, indicated for the treatment of postmenopausal women with osteoporosis who are at increased risk for fracture for whom other treatments aren’t effective or can’t be tolerated. It’s also indicated to increase bone mass in men with osteoporosis at high risk for fracture, treat glucocorticoid-induced osteoporosis in men and women at high risk for fracture, increase bone mass in men at high risk for fracture receiving androgen-deprivation therapy for nonmetastatic prostate cancer, and increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.

This new warning updates a November 2022 alert based on preliminary evidence for a “substantial risk” for hypocalcemia in patients with CKD on dialysis. 

Upon further examination of the data from two trials including more than 500,000 denosumab-treated women with CKD, the FDA concluded that severe hypocalcemia appears to be more common in those with CKD who also have mineral and bone disorder (CKD-MBD). And, for patients with advanced CKD taking denosumab, “severe hypocalcemia resulted in serious harm, including hospitalization, life-threatening events, and death.” 

Most of the severe hypocalcemia events occurred 2-10 weeks after denosumab injection, with the greatest risk during weeks 2-5.

The new warning advises healthcare professionals to assess patients’ kidney function before prescribing denosumab, and for those with advanced CKD, “consider the risk of severe hypocalcemia with Prolia in the context of other available treatments for osteoporosis.”

If the drug is still being considered for those patients for initial or continued use, calcium blood levels should be checked, and patients should be evaluated for CKD-MBD. Prior to prescribing denosumab in these patients, CKD-MBD should be properly managed, hypocalcemia corrected, and patients supplemented with calcium and activated vitamin D to decrease the risk for severe hypocalcemia and associated complications.

“Treatment with denosumab in patients with advanced CKD, including those on dialysis, and particularly patients with diagnosed CKD-MBD should involve a health care provider with expertise in the diagnosis and management of CKD-MBD,” the FDA advises. 

Once denosumab is administered, close monitoring of blood calcium levels and prompt hypocalcemia management is essential to prevent complications including seizures or arrythmias. Patients should be advised to promptly report symptoms that could be consistent with hypocalcemia, including confusion, seizures, irregular heartbeat, fainting, muscle spasms or weakness, face twitching, tingling, or numbness anywhere in the body. 

In 2022, an estimated 2.2 million Prolia prefilled syringes were sold by the manufacturer to US healthcare settings.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has added a boxed warning to the label of the osteoporosis drug denosumab (Prolia) about increased risk for severe hypocalcemia in patients with advanced chronic kidney disease (CKD). 

Denosumab is a monoclonal antibody, indicated for the treatment of postmenopausal women with osteoporosis who are at increased risk for fracture for whom other treatments aren’t effective or can’t be tolerated. It’s also indicated to increase bone mass in men with osteoporosis at high risk for fracture, treat glucocorticoid-induced osteoporosis in men and women at high risk for fracture, increase bone mass in men at high risk for fracture receiving androgen-deprivation therapy for nonmetastatic prostate cancer, and increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.

This new warning updates a November 2022 alert based on preliminary evidence for a “substantial risk” for hypocalcemia in patients with CKD on dialysis. 

Upon further examination of the data from two trials including more than 500,000 denosumab-treated women with CKD, the FDA concluded that severe hypocalcemia appears to be more common in those with CKD who also have mineral and bone disorder (CKD-MBD). And, for patients with advanced CKD taking denosumab, “severe hypocalcemia resulted in serious harm, including hospitalization, life-threatening events, and death.” 

Most of the severe hypocalcemia events occurred 2-10 weeks after denosumab injection, with the greatest risk during weeks 2-5.

The new warning advises healthcare professionals to assess patients’ kidney function before prescribing denosumab, and for those with advanced CKD, “consider the risk of severe hypocalcemia with Prolia in the context of other available treatments for osteoporosis.”

If the drug is still being considered for those patients for initial or continued use, calcium blood levels should be checked, and patients should be evaluated for CKD-MBD. Prior to prescribing denosumab in these patients, CKD-MBD should be properly managed, hypocalcemia corrected, and patients supplemented with calcium and activated vitamin D to decrease the risk for severe hypocalcemia and associated complications.

“Treatment with denosumab in patients with advanced CKD, including those on dialysis, and particularly patients with diagnosed CKD-MBD should involve a health care provider with expertise in the diagnosis and management of CKD-MBD,” the FDA advises. 

Once denosumab is administered, close monitoring of blood calcium levels and prompt hypocalcemia management is essential to prevent complications including seizures or arrythmias. Patients should be advised to promptly report symptoms that could be consistent with hypocalcemia, including confusion, seizures, irregular heartbeat, fainting, muscle spasms or weakness, face twitching, tingling, or numbness anywhere in the body. 

In 2022, an estimated 2.2 million Prolia prefilled syringes were sold by the manufacturer to US healthcare settings.

A version of this article appeared on Medscape.com.

Primary aldosteronism (PA) is a frequently overlooked yet common cause of secondary hypertension, presenting significant risk for cardiovascular morbidity and mortality.

But fewer than 4% of at-risk patients receive the recommended screening for PA, leaving a substantial gap in early detection and management, according to Adina F. Turcu, MD, MS, associate professor in endocrinology and internal medicine at University of Michigan Health in Ann Arbor. 

In response to this clinical challenge, Dr. Turcu and her colleagues developed a best-practice advisory (BPA) to identify patients who were at risk for PA and embedded it into electronic health record at University of Michigan ambulatory clinics. Her team found that use of the tool led to increased rates of screening for PA, particularly among primary care physicians.

Over a 15-month period, Dr. Turcu and her colleagues tested the BPA through a quality improvement study, identifying 14,603 unique candidates for PA screening, with a mean age of 65.5 years and a diverse representation of ethnic backgrounds. 

Notably, 48.1% of these candidates had treatment-resistant hypertension, 43.5% exhibited hypokalemia, 10.5% were younger than 35 years, and 3.1% had adrenal nodules. Of these candidates, 14.0% received orders for PA screening, with 70.5% completing the recommended screening within the system, and 17.4% receiving positive screening results. 

The study, conducted over 6 months in 2023, targeted adults with hypertension and at least one of the following: Those who took four or more antihypertensive medications, exhibited hypokalemia, were younger than age 35 years, or had adrenal nodules. Patients previously tested for PA were excluded from the analysis. 

The noninterruptive BPA was triggered during outpatient visits with clinicians who specialized in hypertension. The advisory would then offer an order set for PA screening and provide a link to interpretation guidance for results. Clinicians had the option to use, ignore, or decline the BPA.

“Although we were hoping for broader uptake of this EHR-embedded BPA, we were delighted to see an increase in PA screening rates to 14% of identified candidates as compared to an average of less than 3% in retrospective studies of similar populations, including in our own institution prior to implementing this BPA,” Dr. Turcu told this news organization.

Physician specialty played a crucial role in the utilization of the BPA. Internists and family medicine physicians accounted for the majority of screening orders, placing 40.0% and 28.1% of these, respectively. Family practitioners and internists predominantly used the embedded order set (80.3% and 68.9%, respectively).

“Hypertension often gets treated rather than screening for [causes of] secondary hypertension prior to treatment,” said Kaniksha Desai, MD, clinical associate professor and endocrinology quality director at Stanford University School of Medicine, Stanford, California, who was not involved in the research. But “primary hyperaldosteronism is a condition that can be treated surgically and has increased long term cardiovascular consequences if not identified. While guidelines recommend screening at-risk patients, this often can get lost in translation in clinical practice due to many factors, including time constraints and volume of patients.” 

Patients who did vs did not undergo screening were more likely to be women, Black, and younger than age 35 years. Additionally, the likelihood of screening was higher among patients with obesity and dyslipidemia, whereas it was lower in those with chronic kidney disease and established cardiovascular complications.

According to Dr. Turcu, the findings from this study suggest that noninterruptive BPAs, especially when integrated into primary care workflows, hold promise as effective tools for PA screening.

When coupled with artificial intelligence to optimize detection yield, these refined BPAs could significantly contribute to personalized care for hypertension, the investigators said. 

“Considering that in the United States almost one in two adults has hypertension, such automatized tools become instrumental to busy clinicians, particularly those in primary care,” Dr. Turcu said. “Our results indicate a promising opportunity to meaningfully improve PA awareness and enhance its diagnosis.” 

Dr. Turcu reported receiving grants from the National Heart, Lung, and Blood Institute and Doris Duke Foundation, served as an investigator in a CinCor Pharma clinical trial, and received financial support to her institution during the conduct of the study. Dr. Desai reported no relevant financial disclosures. 
 

A version of this article appeared on Medscape.com.

Primary aldosteronism (PA) is a frequently overlooked yet common cause of secondary hypertension, presenting significant risk for cardiovascular morbidity and mortality.

But fewer than 4% of at-risk patients receive the recommended screening for PA, leaving a substantial gap in early detection and management, according to Adina F. Turcu, MD, MS, associate professor in endocrinology and internal medicine at University of Michigan Health in Ann Arbor. 

In response to this clinical challenge, Dr. Turcu and her colleagues developed a best-practice advisory (BPA) to identify patients who were at risk for PA and embedded it into electronic health record at University of Michigan ambulatory clinics. Her team found that use of the tool led to increased rates of screening for PA, particularly among primary care physicians.

Over a 15-month period, Dr. Turcu and her colleagues tested the BPA through a quality improvement study, identifying 14,603 unique candidates for PA screening, with a mean age of 65.5 years and a diverse representation of ethnic backgrounds. 

Notably, 48.1% of these candidates had treatment-resistant hypertension, 43.5% exhibited hypokalemia, 10.5% were younger than 35 years, and 3.1% had adrenal nodules. Of these candidates, 14.0% received orders for PA screening, with 70.5% completing the recommended screening within the system, and 17.4% receiving positive screening results. 

The study, conducted over 6 months in 2023, targeted adults with hypertension and at least one of the following: Those who took four or more antihypertensive medications, exhibited hypokalemia, were younger than age 35 years, or had adrenal nodules. Patients previously tested for PA were excluded from the analysis. 

The noninterruptive BPA was triggered during outpatient visits with clinicians who specialized in hypertension. The advisory would then offer an order set for PA screening and provide a link to interpretation guidance for results. Clinicians had the option to use, ignore, or decline the BPA.

“Although we were hoping for broader uptake of this EHR-embedded BPA, we were delighted to see an increase in PA screening rates to 14% of identified candidates as compared to an average of less than 3% in retrospective studies of similar populations, including in our own institution prior to implementing this BPA,” Dr. Turcu told this news organization.

Physician specialty played a crucial role in the utilization of the BPA. Internists and family medicine physicians accounted for the majority of screening orders, placing 40.0% and 28.1% of these, respectively. Family practitioners and internists predominantly used the embedded order set (80.3% and 68.9%, respectively).

“Hypertension often gets treated rather than screening for [causes of] secondary hypertension prior to treatment,” said Kaniksha Desai, MD, clinical associate professor and endocrinology quality director at Stanford University School of Medicine, Stanford, California, who was not involved in the research. But “primary hyperaldosteronism is a condition that can be treated surgically and has increased long term cardiovascular consequences if not identified. While guidelines recommend screening at-risk patients, this often can get lost in translation in clinical practice due to many factors, including time constraints and volume of patients.” 

Patients who did vs did not undergo screening were more likely to be women, Black, and younger than age 35 years. Additionally, the likelihood of screening was higher among patients with obesity and dyslipidemia, whereas it was lower in those with chronic kidney disease and established cardiovascular complications.

According to Dr. Turcu, the findings from this study suggest that noninterruptive BPAs, especially when integrated into primary care workflows, hold promise as effective tools for PA screening.

When coupled with artificial intelligence to optimize detection yield, these refined BPAs could significantly contribute to personalized care for hypertension, the investigators said. 

“Considering that in the United States almost one in two adults has hypertension, such automatized tools become instrumental to busy clinicians, particularly those in primary care,” Dr. Turcu said. “Our results indicate a promising opportunity to meaningfully improve PA awareness and enhance its diagnosis.” 

Dr. Turcu reported receiving grants from the National Heart, Lung, and Blood Institute and Doris Duke Foundation, served as an investigator in a CinCor Pharma clinical trial, and received financial support to her institution during the conduct of the study. Dr. Desai reported no relevant financial disclosures. 
 

A version of this article appeared on Medscape.com.

Primary aldosteronism (PA) is a frequently overlooked yet common cause of secondary hypertension, presenting significant risk for cardiovascular morbidity and mortality.

But fewer than 4% of at-risk patients receive the recommended screening for PA, leaving a substantial gap in early detection and management, according to Adina F. Turcu, MD, MS, associate professor in endocrinology and internal medicine at University of Michigan Health in Ann Arbor. 

In response to this clinical challenge, Dr. Turcu and her colleagues developed a best-practice advisory (BPA) to identify patients who were at risk for PA and embedded it into electronic health record at University of Michigan ambulatory clinics. Her team found that use of the tool led to increased rates of screening for PA, particularly among primary care physicians.

Over a 15-month period, Dr. Turcu and her colleagues tested the BPA through a quality improvement study, identifying 14,603 unique candidates for PA screening, with a mean age of 65.5 years and a diverse representation of ethnic backgrounds. 

Notably, 48.1% of these candidates had treatment-resistant hypertension, 43.5% exhibited hypokalemia, 10.5% were younger than 35 years, and 3.1% had adrenal nodules. Of these candidates, 14.0% received orders for PA screening, with 70.5% completing the recommended screening within the system, and 17.4% receiving positive screening results. 

The study, conducted over 6 months in 2023, targeted adults with hypertension and at least one of the following: Those who took four or more antihypertensive medications, exhibited hypokalemia, were younger than age 35 years, or had adrenal nodules. Patients previously tested for PA were excluded from the analysis. 

The noninterruptive BPA was triggered during outpatient visits with clinicians who specialized in hypertension. The advisory would then offer an order set for PA screening and provide a link to interpretation guidance for results. Clinicians had the option to use, ignore, or decline the BPA.

“Although we were hoping for broader uptake of this EHR-embedded BPA, we were delighted to see an increase in PA screening rates to 14% of identified candidates as compared to an average of less than 3% in retrospective studies of similar populations, including in our own institution prior to implementing this BPA,” Dr. Turcu told this news organization.

Physician specialty played a crucial role in the utilization of the BPA. Internists and family medicine physicians accounted for the majority of screening orders, placing 40.0% and 28.1% of these, respectively. Family practitioners and internists predominantly used the embedded order set (80.3% and 68.9%, respectively).

“Hypertension often gets treated rather than screening for [causes of] secondary hypertension prior to treatment,” said Kaniksha Desai, MD, clinical associate professor and endocrinology quality director at Stanford University School of Medicine, Stanford, California, who was not involved in the research. But “primary hyperaldosteronism is a condition that can be treated surgically and has increased long term cardiovascular consequences if not identified. While guidelines recommend screening at-risk patients, this often can get lost in translation in clinical practice due to many factors, including time constraints and volume of patients.” 

Patients who did vs did not undergo screening were more likely to be women, Black, and younger than age 35 years. Additionally, the likelihood of screening was higher among patients with obesity and dyslipidemia, whereas it was lower in those with chronic kidney disease and established cardiovascular complications.

According to Dr. Turcu, the findings from this study suggest that noninterruptive BPAs, especially when integrated into primary care workflows, hold promise as effective tools for PA screening.

When coupled with artificial intelligence to optimize detection yield, these refined BPAs could significantly contribute to personalized care for hypertension, the investigators said. 

“Considering that in the United States almost one in two adults has hypertension, such automatized tools become instrumental to busy clinicians, particularly those in primary care,” Dr. Turcu said. “Our results indicate a promising opportunity to meaningfully improve PA awareness and enhance its diagnosis.” 

Dr. Turcu reported receiving grants from the National Heart, Lung, and Blood Institute and Doris Duke Foundation, served as an investigator in a CinCor Pharma clinical trial, and received financial support to her institution during the conduct of the study. Dr. Desai reported no relevant financial disclosures. 
 

A version of this article appeared on Medscape.com.

Nearly 37 million Americans, or 15%, have chronic kidney disease (CKD), but 9 in 10 adults with the condition are not aware of their diagnosis. A recent study from Stanford University found that screening asymptomatic adults over the age of 35 years would be a cost-effective strategy for identifying patients with CKD before they develop severe illness. 

What should primary care providers be doing differently? 

The current standard of care is to screen people with underlying conditions that put them at higher risk of developing CKD, most commonly diabetes and hypertension. That’s why the American Diabetes Association recommends annual screening for CKD in patients with type 1 diabetes as well as those with type 2 diabetes. 

And the American Heart Association (AHA) released an advisory last year that defined cardiovascular-kidney-metabolic (CKM) syndrome, a constellation of conditions that often occur together: obesity, diabetes, CKD, and cardiovascular disease. They propose a staged approach to identifying and monitoring CKM throughout the lifespan, which includes regular monitoring of the urine albumin-creatinine ratio in patients who have developed diabetes, hypertension, metabolic syndrome, or any signs of kidney disease.

But despite recognition from the subspecialty professional societies of the importance of screening persons with risk factors — additional conditions are obesity and family history of CKD — real-world implementation lags. 

Sylvia Rosas, MD, is a nephrologist and associate professor of medicine at Harvard University in Cambridge, Massachusetts, who also serves as president of the National Kidney Foundation. In an interview with this news organization, she cited several alarming facts about the state of CKD screening in the United States. 

“Of people with diabetes who have insurance, only 40% get both the glomerular filtration rate (GFR) and the albumin performed, and for those who have hypertension, only 10%,” Dr. Rosas said. She is referring to a urine spot test that measures the amount of albumin in the urine, which is then paired with a serum measurement of creatinine to estimate the glomerular filtration rate. Both tests are needed to detect the asymptomatic stages of CKD, because the presence of albumin in the urine usually precedes drops in the GFR, which indicates more serious disease. 

Dr. Rosas said she is frustrated by the low rate of testing compared with other commonly recommended preventive screenings, given the low cost and simplicity of assessment. Serum creatinine often is obtained as part of a routine chemistry panel, and the albumin test requires a single spot urine test. Yet, in 2018, 61% of US adults aged 50-75 years had received a colonoscopy in the past 10 years. Compared with the high price and inconvenience of undergoing colonoscopy, Dr. Rosas has trouble believing that “we cannot get more than 40% of people [with diabetes] to pee in a cup.” 

But the biggest issue is that if people with risk factors don’t get screened before they develop symptoms of CKD, it is often too late to avoid dialysis or the need for transplantation. 

The early warning symptoms are few, according to Nisha Bansal, MD, a professor in the department of nephrology at the University of Washington in Seattle. “New hypertension is a really important early sign,” Dr. Bansal said. “We know kidney disease almost certainly causes hypertension, so I would definitely think about screening for kidney disease.” Other findings on exam are the appearance of new edema or signs of fluid retention in the hands or around the eyes, along with findings in the urine of albumin, protein, or blood. 

But most patients don’t have any symptoms in the early stages, and they can be nonspecific. “It is fatigue and some nausea,” Dr. Rosas said. “It’s only way at the end that you start vomiting, get itchy, or have hiccups.” Data from the Centers for Disease Control and Prevention have shown that over one third of patients at high risk for kidney failure are unaware of their disease. According to Dr. Rosas, these are patients who often receive the diagnosis of CKD and start dialysis the same day. 
 

Why Not Screen Everyone?

For many conditions, like HIV or different types of cancer, the US Preventive Services Task Force (USPSTF) recommends broad screening of asymptomatic individuals so that early treatment can improve outcomes. 

But when the USPSTF considered the question in 2012 of whether adults should be screened for CKD regardless of symptoms, it found little evidence that early detection could change the course of their illness. At that time, the standard of care for treating early stages of CKD generally focused on treating the comorbid conditions, such as diabetes, hypertension, and cardiovascular disease. 

But the equation has changed with the availability of new drugs to treat CKD, such as sodium-glucose cotransporter 2 (SGLT2) inhibitors and mineralocorticoid receptor antagonists (MRAs).

“I consider these blockbuster drugs,” Dr. Bansal said. “For the first time in decades, we’re showing that this class of medications, the SGLT2 inhibitors, substantially reduce risk of loss of kidney function.”

Expressed in the lumen of the proximal renal tubules, SGLT2 reabsorbs filtered glucose from the tubular lumen. Inhibition of SGLT2 promotes urinary glucose excretion and reduces sodium reabsorption, increasing delivery of sodium to the distal tubule. The first SGLT2 inhibitor, canagliflozin, was approved in 2013 for use as an antihyperglycemic agent but subsequently was shown to have serendipitous benefits for the heart and kidneys. 

Clinical trials have documented reductions in the risk for cardiovascular events in patients with type 2 diabetes, as well as decreases in the risk for progression to end-stage renal disease, cardiovascular mortality, and hospitalization for heart failure. Updated international guidelines from 2022 recommend treating all patients with type 2 diabetes and CKD with an estimated GFR ≥ 20 mL/min/1.73 m2 with an SGLT2 inhibitor. 

But several trials of SGLT2 inhibitors also demonstrated benefits in reducing the risk for cardiovascular-related death or hospitalization for heart failure, even in patients without diabetes. Although initial approval from the US Food and Drug Administration was limited to patients with diabetes and heart failure, the agency has recently expanded its indications to include adults with CKD who do not have diabetes. 

Dr. Bansal said she was happy to see this widening of the indications, which makes more patients eligible to receive SGLT2 inhibitors. “I really think this early CKD group is a great group to consider for those medications,” she said. 

Dr. Bansal also pointed out that MRAs are another class of drugs with an interesting history. Earlier steroidal MRAs were found to have anti-inflammatory and antifibrotic properties, and in 1960 spironolactone was approved for use as a diuretic for the management of edema, primary aldosteronism, and hypertension. But even as their use in cardiology rose, MRAs had less utility for CKD, given adverse events such as hyperkalemia and hormonal effects like gynecomastia. 

But the latest generation of nonsteroidal MRAs (nsMRAs) has higher selectivity for the mineralocorticoid receptor than sex-steroid hormone receptors, reducing androgenic side effects and preventing elevated potassium. Finerenone, the only nsMRA approved in the United States, has been shown in clinical trials to reduce the incidence of cardiovascular events (death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and CKD outcomes, including kidney failure, decrease in estimated GFR, or death from renal causes. 
 

EPIC Changes Coming?

In light of treatment advances that offer hope of preventing progression of CKD in patients identified early, both the National Kidney Foundation and the American Kidney Fund lobbied the USPSTF in 2022 to conduct a fresh review of recent data to evaluate the need for updated screening recommendations. 

The task force completed development of a research plan and collection of public comments in early 2023 and is now reviewing evidence before developing a draft recommendation. 

A team of health policy researchers from Stanford is hoping that some of their recently published work will attract the panel’s attention. The first study, published in 2022, evaluated the cost-effectiveness of dapagliflozin, an SGLT2 inhibitor that has been shown to reduce mortality by 48% in CKD patients without diabetes. 

The Stanford team found that adding dapagliflozin to standard care for these patients improved life expectancy by 2 years and reduced the percentage of those who needed dialysis or kidney transplant from 17% to 11%. 

More recently, Marika Cusick, a doctoral candidate in health policy at the Stanford School of Medicine in Stanford, California, served as first author of an evaluation of the cost-effectiveness of screening asymptomatic adults. “We assessed screening for albuminuria in conjunction with conventional CKD therapy in addition to this new SGLT2 inhibitor class of drugs,” she said. They projected how this might change CKD progression in US adults who are aged 35 or older compared with standard therapy alone. 

The findings were favorable. “A one-time screening would result in a reduction of 398,000 cases of kidney replacement therapy [defined as needing either dialysis or renal transplant] among 158 million US adults who are currently aged 35-75 years,” Ms. Cusick told this news organization.

In terms of quality-adjusted life years (QALYs), a one-time screening at age 55 years yielded an incremental cost-effectiveness ratio of $86,300 per QALY. Screening every 10 years between the ages of 35 and 75 years cost less than $100,000 per QALY gained. 

According to Doug Owens, MD, professor and chair of the department of health policy at Stanford School of Medicine, “There’s a societal decision about how much are we willing to pay for additional length and quality of life. And this fits within what is generally considered reasonable for the US.” 

For example, in the United States, screening for breast cancer among women aged 40-64 years costs $51,000 per QALY, whereas screening for lung cancer using USPSTF guidelines ranges from $72,639 to $156,774 per QALY. 

A former member of the USPSTF, Owens predicted that the current review process would take at least another year. Meanwhile, he and Ms. Cusick are hoping that their work influences the USPSTF to recommend screening asymptomatic adults. “Increasing the awareness of these drugs and their effectiveness is a crucial first step,” he said. 

Although adherence to current recommendations for screening of people at risk is poor, Dr. Rosas suggested that the USPSTF guidelines would be more influential in changing practice among primary care physicians than subspecialty guidelines would. 

“When you have a recommendation like that, they’re putting it in the electronic health record,” she said. By adding best practice alerts to their electronic health record systems, health systems can make it easier for primary care doctors to check all the boxes. 

In line with the AHA’s holistic approach towards managing cardiovascular illnesses, CKD, and metabolic disease, Dr. Bansal suggested an additional strategy: “I think we’re moving toward more interdisciplinary care models, where primary care doctors, nephrologist, cardiologists, and endocrinologists — all of us — should be working together in a collaborative care model, to help break down some of these barriers in terms of screening as well as implementation of these therapies.”

Dr. Bansal, Ms. Cusick, and Dr. Owens reported no financial conflicts of interest. Dr. Rosas receives funding from AstraZeneca and Bayer for serving on advisory boards and clinical research funding, as well as funding from the National Institute of Diabetes and Digestive and Kidney Diseases for clinical trials. 
 

Dr. Thomas is a pediatrician and epidemiologist living in Portland, Oregon.

A version of this article appeared on Medscape.com.

Nearly 37 million Americans, or 15%, have chronic kidney disease (CKD), but 9 in 10 adults with the condition are not aware of their diagnosis. A recent study from Stanford University found that screening asymptomatic adults over the age of 35 years would be a cost-effective strategy for identifying patients with CKD before they develop severe illness. 

What should primary care providers be doing differently? 

The current standard of care is to screen people with underlying conditions that put them at higher risk of developing CKD, most commonly diabetes and hypertension. That’s why the American Diabetes Association recommends annual screening for CKD in patients with type 1 diabetes as well as those with type 2 diabetes. 

And the American Heart Association (AHA) released an advisory last year that defined cardiovascular-kidney-metabolic (CKM) syndrome, a constellation of conditions that often occur together: obesity, diabetes, CKD, and cardiovascular disease. They propose a staged approach to identifying and monitoring CKM throughout the lifespan, which includes regular monitoring of the urine albumin-creatinine ratio in patients who have developed diabetes, hypertension, metabolic syndrome, or any signs of kidney disease.

But despite recognition from the subspecialty professional societies of the importance of screening persons with risk factors — additional conditions are obesity and family history of CKD — real-world implementation lags. 

Sylvia Rosas, MD, is a nephrologist and associate professor of medicine at Harvard University in Cambridge, Massachusetts, who also serves as president of the National Kidney Foundation. In an interview with this news organization, she cited several alarming facts about the state of CKD screening in the United States. 

“Of people with diabetes who have insurance, only 40% get both the glomerular filtration rate (GFR) and the albumin performed, and for those who have hypertension, only 10%,” Dr. Rosas said. She is referring to a urine spot test that measures the amount of albumin in the urine, which is then paired with a serum measurement of creatinine to estimate the glomerular filtration rate. Both tests are needed to detect the asymptomatic stages of CKD, because the presence of albumin in the urine usually precedes drops in the GFR, which indicates more serious disease. 

Dr. Rosas said she is frustrated by the low rate of testing compared with other commonly recommended preventive screenings, given the low cost and simplicity of assessment. Serum creatinine often is obtained as part of a routine chemistry panel, and the albumin test requires a single spot urine test. Yet, in 2018, 61% of US adults aged 50-75 years had received a colonoscopy in the past 10 years. Compared with the high price and inconvenience of undergoing colonoscopy, Dr. Rosas has trouble believing that “we cannot get more than 40% of people [with diabetes] to pee in a cup.” 

But the biggest issue is that if people with risk factors don’t get screened before they develop symptoms of CKD, it is often too late to avoid dialysis or the need for transplantation. 

The early warning symptoms are few, according to Nisha Bansal, MD, a professor in the department of nephrology at the University of Washington in Seattle. “New hypertension is a really important early sign,” Dr. Bansal said. “We know kidney disease almost certainly causes hypertension, so I would definitely think about screening for kidney disease.” Other findings on exam are the appearance of new edema or signs of fluid retention in the hands or around the eyes, along with findings in the urine of albumin, protein, or blood. 

But most patients don’t have any symptoms in the early stages, and they can be nonspecific. “It is fatigue and some nausea,” Dr. Rosas said. “It’s only way at the end that you start vomiting, get itchy, or have hiccups.” Data from the Centers for Disease Control and Prevention have shown that over one third of patients at high risk for kidney failure are unaware of their disease. According to Dr. Rosas, these are patients who often receive the diagnosis of CKD and start dialysis the same day. 
 

Why Not Screen Everyone?

For many conditions, like HIV or different types of cancer, the US Preventive Services Task Force (USPSTF) recommends broad screening of asymptomatic individuals so that early treatment can improve outcomes. 

But when the USPSTF considered the question in 2012 of whether adults should be screened for CKD regardless of symptoms, it found little evidence that early detection could change the course of their illness. At that time, the standard of care for treating early stages of CKD generally focused on treating the comorbid conditions, such as diabetes, hypertension, and cardiovascular disease. 

But the equation has changed with the availability of new drugs to treat CKD, such as sodium-glucose cotransporter 2 (SGLT2) inhibitors and mineralocorticoid receptor antagonists (MRAs).

“I consider these blockbuster drugs,” Dr. Bansal said. “For the first time in decades, we’re showing that this class of medications, the SGLT2 inhibitors, substantially reduce risk of loss of kidney function.”

Expressed in the lumen of the proximal renal tubules, SGLT2 reabsorbs filtered glucose from the tubular lumen. Inhibition of SGLT2 promotes urinary glucose excretion and reduces sodium reabsorption, increasing delivery of sodium to the distal tubule. The first SGLT2 inhibitor, canagliflozin, was approved in 2013 for use as an antihyperglycemic agent but subsequently was shown to have serendipitous benefits for the heart and kidneys. 

Clinical trials have documented reductions in the risk for cardiovascular events in patients with type 2 diabetes, as well as decreases in the risk for progression to end-stage renal disease, cardiovascular mortality, and hospitalization for heart failure. Updated international guidelines from 2022 recommend treating all patients with type 2 diabetes and CKD with an estimated GFR ≥ 20 mL/min/1.73 m2 with an SGLT2 inhibitor. 

But several trials of SGLT2 inhibitors also demonstrated benefits in reducing the risk for cardiovascular-related death or hospitalization for heart failure, even in patients without diabetes. Although initial approval from the US Food and Drug Administration was limited to patients with diabetes and heart failure, the agency has recently expanded its indications to include adults with CKD who do not have diabetes. 

Dr. Bansal said she was happy to see this widening of the indications, which makes more patients eligible to receive SGLT2 inhibitors. “I really think this early CKD group is a great group to consider for those medications,” she said. 

Dr. Bansal also pointed out that MRAs are another class of drugs with an interesting history. Earlier steroidal MRAs were found to have anti-inflammatory and antifibrotic properties, and in 1960 spironolactone was approved for use as a diuretic for the management of edema, primary aldosteronism, and hypertension. But even as their use in cardiology rose, MRAs had less utility for CKD, given adverse events such as hyperkalemia and hormonal effects like gynecomastia. 

But the latest generation of nonsteroidal MRAs (nsMRAs) has higher selectivity for the mineralocorticoid receptor than sex-steroid hormone receptors, reducing androgenic side effects and preventing elevated potassium. Finerenone, the only nsMRA approved in the United States, has been shown in clinical trials to reduce the incidence of cardiovascular events (death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and CKD outcomes, including kidney failure, decrease in estimated GFR, or death from renal causes. 
 

EPIC Changes Coming?

In light of treatment advances that offer hope of preventing progression of CKD in patients identified early, both the National Kidney Foundation and the American Kidney Fund lobbied the USPSTF in 2022 to conduct a fresh review of recent data to evaluate the need for updated screening recommendations. 

The task force completed development of a research plan and collection of public comments in early 2023 and is now reviewing evidence before developing a draft recommendation. 

A team of health policy researchers from Stanford is hoping that some of their recently published work will attract the panel’s attention. The first study, published in 2022, evaluated the cost-effectiveness of dapagliflozin, an SGLT2 inhibitor that has been shown to reduce mortality by 48% in CKD patients without diabetes. 

The Stanford team found that adding dapagliflozin to standard care for these patients improved life expectancy by 2 years and reduced the percentage of those who needed dialysis or kidney transplant from 17% to 11%. 

More recently, Marika Cusick, a doctoral candidate in health policy at the Stanford School of Medicine in Stanford, California, served as first author of an evaluation of the cost-effectiveness of screening asymptomatic adults. “We assessed screening for albuminuria in conjunction with conventional CKD therapy in addition to this new SGLT2 inhibitor class of drugs,” she said. They projected how this might change CKD progression in US adults who are aged 35 or older compared with standard therapy alone. 

The findings were favorable. “A one-time screening would result in a reduction of 398,000 cases of kidney replacement therapy [defined as needing either dialysis or renal transplant] among 158 million US adults who are currently aged 35-75 years,” Ms. Cusick told this news organization.

In terms of quality-adjusted life years (QALYs), a one-time screening at age 55 years yielded an incremental cost-effectiveness ratio of $86,300 per QALY. Screening every 10 years between the ages of 35 and 75 years cost less than $100,000 per QALY gained. 

According to Doug Owens, MD, professor and chair of the department of health policy at Stanford School of Medicine, “There’s a societal decision about how much are we willing to pay for additional length and quality of life. And this fits within what is generally considered reasonable for the US.” 

For example, in the United States, screening for breast cancer among women aged 40-64 years costs $51,000 per QALY, whereas screening for lung cancer using USPSTF guidelines ranges from $72,639 to $156,774 per QALY. 

A former member of the USPSTF, Owens predicted that the current review process would take at least another year. Meanwhile, he and Ms. Cusick are hoping that their work influences the USPSTF to recommend screening asymptomatic adults. “Increasing the awareness of these drugs and their effectiveness is a crucial first step,” he said. 

Although adherence to current recommendations for screening of people at risk is poor, Dr. Rosas suggested that the USPSTF guidelines would be more influential in changing practice among primary care physicians than subspecialty guidelines would. 

“When you have a recommendation like that, they’re putting it in the electronic health record,” she said. By adding best practice alerts to their electronic health record systems, health systems can make it easier for primary care doctors to check all the boxes. 

In line with the AHA’s holistic approach towards managing cardiovascular illnesses, CKD, and metabolic disease, Dr. Bansal suggested an additional strategy: “I think we’re moving toward more interdisciplinary care models, where primary care doctors, nephrologist, cardiologists, and endocrinologists — all of us — should be working together in a collaborative care model, to help break down some of these barriers in terms of screening as well as implementation of these therapies.”

Dr. Bansal, Ms. Cusick, and Dr. Owens reported no financial conflicts of interest. Dr. Rosas receives funding from AstraZeneca and Bayer for serving on advisory boards and clinical research funding, as well as funding from the National Institute of Diabetes and Digestive and Kidney Diseases for clinical trials. 
 

Dr. Thomas is a pediatrician and epidemiologist living in Portland, Oregon.

A version of this article appeared on Medscape.com.

Nearly 37 million Americans, or 15%, have chronic kidney disease (CKD), but 9 in 10 adults with the condition are not aware of their diagnosis. A recent study from Stanford University found that screening asymptomatic adults over the age of 35 years would be a cost-effective strategy for identifying patients with CKD before they develop severe illness. 

What should primary care providers be doing differently? 

The current standard of care is to screen people with underlying conditions that put them at higher risk of developing CKD, most commonly diabetes and hypertension. That’s why the American Diabetes Association recommends annual screening for CKD in patients with type 1 diabetes as well as those with type 2 diabetes. 

And the American Heart Association (AHA) released an advisory last year that defined cardiovascular-kidney-metabolic (CKM) syndrome, a constellation of conditions that often occur together: obesity, diabetes, CKD, and cardiovascular disease. They propose a staged approach to identifying and monitoring CKM throughout the lifespan, which includes regular monitoring of the urine albumin-creatinine ratio in patients who have developed diabetes, hypertension, metabolic syndrome, or any signs of kidney disease.

But despite recognition from the subspecialty professional societies of the importance of screening persons with risk factors — additional conditions are obesity and family history of CKD — real-world implementation lags. 

Sylvia Rosas, MD, is a nephrologist and associate professor of medicine at Harvard University in Cambridge, Massachusetts, who also serves as president of the National Kidney Foundation. In an interview with this news organization, she cited several alarming facts about the state of CKD screening in the United States. 

“Of people with diabetes who have insurance, only 40% get both the glomerular filtration rate (GFR) and the albumin performed, and for those who have hypertension, only 10%,” Dr. Rosas said. She is referring to a urine spot test that measures the amount of albumin in the urine, which is then paired with a serum measurement of creatinine to estimate the glomerular filtration rate. Both tests are needed to detect the asymptomatic stages of CKD, because the presence of albumin in the urine usually precedes drops in the GFR, which indicates more serious disease. 

Dr. Rosas said she is frustrated by the low rate of testing compared with other commonly recommended preventive screenings, given the low cost and simplicity of assessment. Serum creatinine often is obtained as part of a routine chemistry panel, and the albumin test requires a single spot urine test. Yet, in 2018, 61% of US adults aged 50-75 years had received a colonoscopy in the past 10 years. Compared with the high price and inconvenience of undergoing colonoscopy, Dr. Rosas has trouble believing that “we cannot get more than 40% of people [with diabetes] to pee in a cup.” 

But the biggest issue is that if people with risk factors don’t get screened before they develop symptoms of CKD, it is often too late to avoid dialysis or the need for transplantation. 

The early warning symptoms are few, according to Nisha Bansal, MD, a professor in the department of nephrology at the University of Washington in Seattle. “New hypertension is a really important early sign,” Dr. Bansal said. “We know kidney disease almost certainly causes hypertension, so I would definitely think about screening for kidney disease.” Other findings on exam are the appearance of new edema or signs of fluid retention in the hands or around the eyes, along with findings in the urine of albumin, protein, or blood. 

But most patients don’t have any symptoms in the early stages, and they can be nonspecific. “It is fatigue and some nausea,” Dr. Rosas said. “It’s only way at the end that you start vomiting, get itchy, or have hiccups.” Data from the Centers for Disease Control and Prevention have shown that over one third of patients at high risk for kidney failure are unaware of their disease. According to Dr. Rosas, these are patients who often receive the diagnosis of CKD and start dialysis the same day. 
 

Why Not Screen Everyone?

For many conditions, like HIV or different types of cancer, the US Preventive Services Task Force (USPSTF) recommends broad screening of asymptomatic individuals so that early treatment can improve outcomes. 

But when the USPSTF considered the question in 2012 of whether adults should be screened for CKD regardless of symptoms, it found little evidence that early detection could change the course of their illness. At that time, the standard of care for treating early stages of CKD generally focused on treating the comorbid conditions, such as diabetes, hypertension, and cardiovascular disease. 

But the equation has changed with the availability of new drugs to treat CKD, such as sodium-glucose cotransporter 2 (SGLT2) inhibitors and mineralocorticoid receptor antagonists (MRAs).

“I consider these blockbuster drugs,” Dr. Bansal said. “For the first time in decades, we’re showing that this class of medications, the SGLT2 inhibitors, substantially reduce risk of loss of kidney function.”

Expressed in the lumen of the proximal renal tubules, SGLT2 reabsorbs filtered glucose from the tubular lumen. Inhibition of SGLT2 promotes urinary glucose excretion and reduces sodium reabsorption, increasing delivery of sodium to the distal tubule. The first SGLT2 inhibitor, canagliflozin, was approved in 2013 for use as an antihyperglycemic agent but subsequently was shown to have serendipitous benefits for the heart and kidneys. 

Clinical trials have documented reductions in the risk for cardiovascular events in patients with type 2 diabetes, as well as decreases in the risk for progression to end-stage renal disease, cardiovascular mortality, and hospitalization for heart failure. Updated international guidelines from 2022 recommend treating all patients with type 2 diabetes and CKD with an estimated GFR ≥ 20 mL/min/1.73 m2 with an SGLT2 inhibitor. 

But several trials of SGLT2 inhibitors also demonstrated benefits in reducing the risk for cardiovascular-related death or hospitalization for heart failure, even in patients without diabetes. Although initial approval from the US Food and Drug Administration was limited to patients with diabetes and heart failure, the agency has recently expanded its indications to include adults with CKD who do not have diabetes. 

Dr. Bansal said she was happy to see this widening of the indications, which makes more patients eligible to receive SGLT2 inhibitors. “I really think this early CKD group is a great group to consider for those medications,” she said. 

Dr. Bansal also pointed out that MRAs are another class of drugs with an interesting history. Earlier steroidal MRAs were found to have anti-inflammatory and antifibrotic properties, and in 1960 spironolactone was approved for use as a diuretic for the management of edema, primary aldosteronism, and hypertension. But even as their use in cardiology rose, MRAs had less utility for CKD, given adverse events such as hyperkalemia and hormonal effects like gynecomastia. 

But the latest generation of nonsteroidal MRAs (nsMRAs) has higher selectivity for the mineralocorticoid receptor than sex-steroid hormone receptors, reducing androgenic side effects and preventing elevated potassium. Finerenone, the only nsMRA approved in the United States, has been shown in clinical trials to reduce the incidence of cardiovascular events (death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and CKD outcomes, including kidney failure, decrease in estimated GFR, or death from renal causes. 
 

EPIC Changes Coming?

In light of treatment advances that offer hope of preventing progression of CKD in patients identified early, both the National Kidney Foundation and the American Kidney Fund lobbied the USPSTF in 2022 to conduct a fresh review of recent data to evaluate the need for updated screening recommendations. 

The task force completed development of a research plan and collection of public comments in early 2023 and is now reviewing evidence before developing a draft recommendation. 

A team of health policy researchers from Stanford is hoping that some of their recently published work will attract the panel’s attention. The first study, published in 2022, evaluated the cost-effectiveness of dapagliflozin, an SGLT2 inhibitor that has been shown to reduce mortality by 48% in CKD patients without diabetes. 

The Stanford team found that adding dapagliflozin to standard care for these patients improved life expectancy by 2 years and reduced the percentage of those who needed dialysis or kidney transplant from 17% to 11%. 

More recently, Marika Cusick, a doctoral candidate in health policy at the Stanford School of Medicine in Stanford, California, served as first author of an evaluation of the cost-effectiveness of screening asymptomatic adults. “We assessed screening for albuminuria in conjunction with conventional CKD therapy in addition to this new SGLT2 inhibitor class of drugs,” she said. They projected how this might change CKD progression in US adults who are aged 35 or older compared with standard therapy alone. 

The findings were favorable. “A one-time screening would result in a reduction of 398,000 cases of kidney replacement therapy [defined as needing either dialysis or renal transplant] among 158 million US adults who are currently aged 35-75 years,” Ms. Cusick told this news organization.

In terms of quality-adjusted life years (QALYs), a one-time screening at age 55 years yielded an incremental cost-effectiveness ratio of $86,300 per QALY. Screening every 10 years between the ages of 35 and 75 years cost less than $100,000 per QALY gained. 

According to Doug Owens, MD, professor and chair of the department of health policy at Stanford School of Medicine, “There’s a societal decision about how much are we willing to pay for additional length and quality of life. And this fits within what is generally considered reasonable for the US.” 

For example, in the United States, screening for breast cancer among women aged 40-64 years costs $51,000 per QALY, whereas screening for lung cancer using USPSTF guidelines ranges from $72,639 to $156,774 per QALY. 

A former member of the USPSTF, Owens predicted that the current review process would take at least another year. Meanwhile, he and Ms. Cusick are hoping that their work influences the USPSTF to recommend screening asymptomatic adults. “Increasing the awareness of these drugs and their effectiveness is a crucial first step,” he said. 

Although adherence to current recommendations for screening of people at risk is poor, Dr. Rosas suggested that the USPSTF guidelines would be more influential in changing practice among primary care physicians than subspecialty guidelines would. 

“When you have a recommendation like that, they’re putting it in the electronic health record,” she said. By adding best practice alerts to their electronic health record systems, health systems can make it easier for primary care doctors to check all the boxes. 

In line with the AHA’s holistic approach towards managing cardiovascular illnesses, CKD, and metabolic disease, Dr. Bansal suggested an additional strategy: “I think we’re moving toward more interdisciplinary care models, where primary care doctors, nephrologist, cardiologists, and endocrinologists — all of us — should be working together in a collaborative care model, to help break down some of these barriers in terms of screening as well as implementation of these therapies.”

Dr. Bansal, Ms. Cusick, and Dr. Owens reported no financial conflicts of interest. Dr. Rosas receives funding from AstraZeneca and Bayer for serving on advisory boards and clinical research funding, as well as funding from the National Institute of Diabetes and Digestive and Kidney Diseases for clinical trials. 
 

Dr. Thomas is a pediatrician and epidemiologist living in Portland, Oregon.

A version of this article appeared on Medscape.com.

TOPLINE:

Previous gestational diabetes mellitus (GDM) nearly doubles future chronic kidney disease (CKD) risk, irrespective of subsequent diabetes and hypertension, a study showed.

METHODOLOGY:

• A nationwide, cohort study was based on data from the Danish Medical Birth Register and included 697,622 women who gave birth between 1997 and 2018.
• Of all study participants, 3.4% reported GDM in at least one pregnancy, and 12.8% of women with GDM received insulin, a proxy for a more severe metabolic dysfunction.
• The women were followed up for a median of 11.9 years.
• Researchers studied CKD and acute kidney disease as the outcomes of interest, the mediating effects of subsequent diabetes and hypertension on future CKD, and how GDM severity affected later risk for kidney disease.

TAKEAWAY:

• Women with GDM showed significantly higher CKD risk than those without GDM (adjusted hazard ratio [aHR], 1.92; 95% CI, 1.67-2.21).
• Women who received insulin during pregnancy due to severe metabolic dysfunction but did not develop subsequent diabetes had a proportionally higher risk for CKD (aHR, 2.35; 95% CI, 1.39-3.97).
• Women with GDM who went on to develop diabetes or hypertension faced even higher risks for CKD, suggesting that preventing diabetes and hypertension after GDM may reduce the development of CKD.
• GDM did not affect the risk for acute kidney disease (aHR, 1.08; 95% CI, 0.90-1.29).

IN PRACTICE:

“Women with severe metabolic dysfunction during pregnancy constitute a high-risk group regarding future CKD,” the authors wrote. “The significantly elevated CKD risk was observed from 2 years after pregnancy and beyond.”

SOURCE:

The study, with first author Maria Hornstrup Christensen, of Odense University Hospital, Odense, Denmark, was published online on December 15 in Diabetes Care.

LIMITATIONS:

GDM may be underdiagnosed, and undiagnosed diabetes may be misclassified as GDM. The proxies of GDM and insulin treatment may not have captured the increasing severity of metabolic dysfunction. The prevalence of insulin treatment was lower than expected, perhaps due to the practice of providing a patient’s first insulin pen without a prescription and perhaps not recording it in a patient’s health record.

DISCLOSURES:

This work received financial support from the University of Southern Denmark, the Region of Southern Denmark, and the Danish Diabetes Academy, which is funded by the Novo Nordisk Foundation. The authors declared no conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Previous gestational diabetes mellitus (GDM) nearly doubles future chronic kidney disease (CKD) risk, irrespective of subsequent diabetes and hypertension, a study showed.

METHODOLOGY:

• A nationwide, cohort study was based on data from the Danish Medical Birth Register and included 697,622 women who gave birth between 1997 and 2018.
• Of all study participants, 3.4% reported GDM in at least one pregnancy, and 12.8% of women with GDM received insulin, a proxy for a more severe metabolic dysfunction.
• The women were followed up for a median of 11.9 years.
• Researchers studied CKD and acute kidney disease as the outcomes of interest, the mediating effects of subsequent diabetes and hypertension on future CKD, and how GDM severity affected later risk for kidney disease.

TAKEAWAY:

• Women with GDM showed significantly higher CKD risk than those without GDM (adjusted hazard ratio [aHR], 1.92; 95% CI, 1.67-2.21).
• Women who received insulin during pregnancy due to severe metabolic dysfunction but did not develop subsequent diabetes had a proportionally higher risk for CKD (aHR, 2.35; 95% CI, 1.39-3.97).
• Women with GDM who went on to develop diabetes or hypertension faced even higher risks for CKD, suggesting that preventing diabetes and hypertension after GDM may reduce the development of CKD.
• GDM did not affect the risk for acute kidney disease (aHR, 1.08; 95% CI, 0.90-1.29).

IN PRACTICE:

“Women with severe metabolic dysfunction during pregnancy constitute a high-risk group regarding future CKD,” the authors wrote. “The significantly elevated CKD risk was observed from 2 years after pregnancy and beyond.”

SOURCE:

The study, with first author Maria Hornstrup Christensen, of Odense University Hospital, Odense, Denmark, was published online on December 15 in Diabetes Care.

LIMITATIONS:

GDM may be underdiagnosed, and undiagnosed diabetes may be misclassified as GDM. The proxies of GDM and insulin treatment may not have captured the increasing severity of metabolic dysfunction. The prevalence of insulin treatment was lower than expected, perhaps due to the practice of providing a patient’s first insulin pen without a prescription and perhaps not recording it in a patient’s health record.

DISCLOSURES:

This work received financial support from the University of Southern Denmark, the Region of Southern Denmark, and the Danish Diabetes Academy, which is funded by the Novo Nordisk Foundation. The authors declared no conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Previous gestational diabetes mellitus (GDM) nearly doubles future chronic kidney disease (CKD) risk, irrespective of subsequent diabetes and hypertension, a study showed.

METHODOLOGY:

• A nationwide, cohort study was based on data from the Danish Medical Birth Register and included 697,622 women who gave birth between 1997 and 2018.
• Of all study participants, 3.4% reported GDM in at least one pregnancy, and 12.8% of women with GDM received insulin, a proxy for a more severe metabolic dysfunction.
• The women were followed up for a median of 11.9 years.
• Researchers studied CKD and acute kidney disease as the outcomes of interest, the mediating effects of subsequent diabetes and hypertension on future CKD, and how GDM severity affected later risk for kidney disease.

TAKEAWAY:

• Women with GDM showed significantly higher CKD risk than those without GDM (adjusted hazard ratio [aHR], 1.92; 95% CI, 1.67-2.21).
• Women who received insulin during pregnancy due to severe metabolic dysfunction but did not develop subsequent diabetes had a proportionally higher risk for CKD (aHR, 2.35; 95% CI, 1.39-3.97).
• Women with GDM who went on to develop diabetes or hypertension faced even higher risks for CKD, suggesting that preventing diabetes and hypertension after GDM may reduce the development of CKD.
• GDM did not affect the risk for acute kidney disease (aHR, 1.08; 95% CI, 0.90-1.29).

IN PRACTICE:

“Women with severe metabolic dysfunction during pregnancy constitute a high-risk group regarding future CKD,” the authors wrote. “The significantly elevated CKD risk was observed from 2 years after pregnancy and beyond.”

SOURCE:

The study, with first author Maria Hornstrup Christensen, of Odense University Hospital, Odense, Denmark, was published online on December 15 in Diabetes Care.

LIMITATIONS:

GDM may be underdiagnosed, and undiagnosed diabetes may be misclassified as GDM. The proxies of GDM and insulin treatment may not have captured the increasing severity of metabolic dysfunction. The prevalence of insulin treatment was lower than expected, perhaps due to the practice of providing a patient’s first insulin pen without a prescription and perhaps not recording it in a patient’s health record.

DISCLOSURES:

This work received financial support from the University of Southern Denmark, the Region of Southern Denmark, and the Danish Diabetes Academy, which is funded by the Novo Nordisk Foundation. The authors declared no conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with type 2 diabetes (T2D) at an elevated risk for kidney failure may stand to gain the most renal benefit with intensive glycemic control, but they also face the highest overall risk for death and hypoglycemic events.

METHODOLOGY:

• Studies show the primary benefit of intensive glycemic control in T2D is microvascular outcomes, mostly in the kidney, but no clear criteria exist to identify patients who may benefit most.
• Researchers conducted a post hoc analysis of the ACCORD trial, including 9777 patients with diabetes and cardiovascular disease or two or more cardiovascular risk factors.
• The 5-year kidney failure risk was estimated using the validated kidney failure risk equation (KFRE).
• The patients were randomly assigned to receive intensive glycemic control (A1c, < 6.0%) or standard glycemic control (A1c, 7.0%-7.9%).
• The primary outcomes were kidney microvascular events and all-cause mortality.

TAKEAWAY:

• Over a 7-year period, intensive vs standard glycemic control delayed the onset of kidney microvascular outcomes by 48.4 days (corresponding hazard ratio [HR], 0.75; 95% CI, 0.65-0.86) but reduced the time to death by 23.6 days (HR, 1.20; 95% CI, 1.04-1.40).
• Patients in the highest quartile of 5-year kidney failure risk according to KFRE benefited the most with intensive vs standard glycemic control and reported the longest delay in the onset of kidney microvascular outcomes (114.8 days; 95% CI, 58.1-176.4).
• Although renal outcomes improved, the time to death was shortened by 56.7 days in patients with elevated risk for kidney failure receiving intensive glycemic control.

IN PRACTICE:

“The observed effect of intensive glycemic control on kidney microvascular outcomes in ACCORD is almost entirely driven by a subset of patients representing one quarter of the trial eligible population at elevated risk for kidney failure at baseline,” the authors wrote.

SOURCE:

Vivek Charu of Stanford University School of Medicine, Stanford, California, led this study, which was published online on December 11, 2023, in the Journal of the American Society of Nephrology

LIMITATIONS:

The ACCORD study enrolled participants with a low risk for kidney disease. Therefore, this study lacks relevant data that might be needed to analyze the risks and benefits of intensive glycemic control in a population at high risk for kidney disease. Treatment options and monitoring approaches to glycemic control have evolved in the nearly 20 years since the ACCORD trial, which used insulin and sulfonylurea agents for glycemic control.

DISCLOSURES:

This work was supported by several grants secured by the authors. Some authors declared serving in advisory or leadership roles, receiving honoraria and research funding, and other ties with several sources.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with type 2 diabetes (T2D) at an elevated risk for kidney failure may stand to gain the most renal benefit with intensive glycemic control, but they also face the highest overall risk for death and hypoglycemic events.

METHODOLOGY:

• Studies show the primary benefit of intensive glycemic control in T2D is microvascular outcomes, mostly in the kidney, but no clear criteria exist to identify patients who may benefit most.
• Researchers conducted a post hoc analysis of the ACCORD trial, including 9777 patients with diabetes and cardiovascular disease or two or more cardiovascular risk factors.
• The 5-year kidney failure risk was estimated using the validated kidney failure risk equation (KFRE).
• The patients were randomly assigned to receive intensive glycemic control (A1c, < 6.0%) or standard glycemic control (A1c, 7.0%-7.9%).
• The primary outcomes were kidney microvascular events and all-cause mortality.

TAKEAWAY:

• Over a 7-year period, intensive vs standard glycemic control delayed the onset of kidney microvascular outcomes by 48.4 days (corresponding hazard ratio [HR], 0.75; 95% CI, 0.65-0.86) but reduced the time to death by 23.6 days (HR, 1.20; 95% CI, 1.04-1.40).
• Patients in the highest quartile of 5-year kidney failure risk according to KFRE benefited the most with intensive vs standard glycemic control and reported the longest delay in the onset of kidney microvascular outcomes (114.8 days; 95% CI, 58.1-176.4).
• Although renal outcomes improved, the time to death was shortened by 56.7 days in patients with elevated risk for kidney failure receiving intensive glycemic control.

IN PRACTICE:

“The observed effect of intensive glycemic control on kidney microvascular outcomes in ACCORD is almost entirely driven by a subset of patients representing one quarter of the trial eligible population at elevated risk for kidney failure at baseline,” the authors wrote.

SOURCE:

Vivek Charu of Stanford University School of Medicine, Stanford, California, led this study, which was published online on December 11, 2023, in the Journal of the American Society of Nephrology

LIMITATIONS:

The ACCORD study enrolled participants with a low risk for kidney disease. Therefore, this study lacks relevant data that might be needed to analyze the risks and benefits of intensive glycemic control in a population at high risk for kidney disease. Treatment options and monitoring approaches to glycemic control have evolved in the nearly 20 years since the ACCORD trial, which used insulin and sulfonylurea agents for glycemic control.

DISCLOSURES:

This work was supported by several grants secured by the authors. Some authors declared serving in advisory or leadership roles, receiving honoraria and research funding, and other ties with several sources.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with type 2 diabetes (T2D) at an elevated risk for kidney failure may stand to gain the most renal benefit with intensive glycemic control, but they also face the highest overall risk for death and hypoglycemic events.

METHODOLOGY:

• Studies show the primary benefit of intensive glycemic control in T2D is microvascular outcomes, mostly in the kidney, but no clear criteria exist to identify patients who may benefit most.
• Researchers conducted a post hoc analysis of the ACCORD trial, including 9777 patients with diabetes and cardiovascular disease or two or more cardiovascular risk factors.
• The 5-year kidney failure risk was estimated using the validated kidney failure risk equation (KFRE).
• The patients were randomly assigned to receive intensive glycemic control (A1c, < 6.0%) or standard glycemic control (A1c, 7.0%-7.9%).
• The primary outcomes were kidney microvascular events and all-cause mortality.

TAKEAWAY:

• Over a 7-year period, intensive vs standard glycemic control delayed the onset of kidney microvascular outcomes by 48.4 days (corresponding hazard ratio [HR], 0.75; 95% CI, 0.65-0.86) but reduced the time to death by 23.6 days (HR, 1.20; 95% CI, 1.04-1.40).
• Patients in the highest quartile of 5-year kidney failure risk according to KFRE benefited the most with intensive vs standard glycemic control and reported the longest delay in the onset of kidney microvascular outcomes (114.8 days; 95% CI, 58.1-176.4).
• Although renal outcomes improved, the time to death was shortened by 56.7 days in patients with elevated risk for kidney failure receiving intensive glycemic control.

IN PRACTICE:

“The observed effect of intensive glycemic control on kidney microvascular outcomes in ACCORD is almost entirely driven by a subset of patients representing one quarter of the trial eligible population at elevated risk for kidney failure at baseline,” the authors wrote.

SOURCE:

Vivek Charu of Stanford University School of Medicine, Stanford, California, led this study, which was published online on December 11, 2023, in the Journal of the American Society of Nephrology

LIMITATIONS:

The ACCORD study enrolled participants with a low risk for kidney disease. Therefore, this study lacks relevant data that might be needed to analyze the risks and benefits of intensive glycemic control in a population at high risk for kidney disease. Treatment options and monitoring approaches to glycemic control have evolved in the nearly 20 years since the ACCORD trial, which used insulin and sulfonylurea agents for glycemic control.

DISCLOSURES:

This work was supported by several grants secured by the authors. Some authors declared serving in advisory or leadership roles, receiving honoraria and research funding, and other ties with several sources.

A version of this article appeared on Medscape.com.

Over just a decade, sodium-glucose cotransporter-2 (SGLT2) inhibitors have revolutionized the second-line treatment of type 2 diabetes by improving the control of blood sugar, and they’re also being used to treat heart failure and chronic kidney disease. Now, there’s growing evidence that the medications have the potential to play a role in the treatment of a variety of rheumatologic diseases — gout, systemic lupus erythematosus (SLE), and lupus nephritis.

“I suspect that SGLT2 inhibitors may have a role in multiple rheumatic diseases,” said rheumatologist April Jorge, MD, of Harvard Medical School and Massachusetts General Hospital, Boston.

Jorge_April_MA_2_web.jpg

In gout, for example, “SGLT2 inhibitors hold great promise as a multipurpose treatment option,” said rheumatologist Chio Yokose, MD, MSc, also of Harvard Medical School and Massachusetts General Hospital. Both Dr. Jorge and Dr. Yokose spoke at recent medical conferences and in interviews about the potential value of the drugs in rheumatology.
 

There’s a big caveat. For the moment, SGLT2 inhibitors aren’t cleared for use in the treatment of rheumatologic conditions, and neither physician is ready to recommend prescribing them off-label outside of their FDA-approved indications.

But studies could pave the way toward more approved uses in rheumatology. And there’s good news for now: Many rheumatology patients may already be eligible to take the drugs because of other medical conditions. In gout, for example, “sizable proportions of patients have comorbidities for which they are already indicated,” Dr. Yokose said.
 

Research Hints at Gout-Busting Potential

The first SGLT2 inhibitor canagliflozin (Invokana), received FDA approval in 2013, followed by dapagliflozin (Farxiga), empagliflozin (Jardiance), ertugliflozin (Steglatro), and bexagliflozin (Brenzavvy). The drugs “lower blood sugar by causing the kidneys to remove sugar from the body through urine,” reports the National Kidney Foundation, and they “help to protect the kidneys and heart in people with CKD [chronic kidney disease].”

Yokose_Chio_MA_web.jpg

As Dr. Yokose noted in a presentation at the 2023 Gout Hyperuricemia and Crystal Associated Disease Network research symposium, SGLT2 inhibitors “have really become blockbuster drugs, and they’ve now been integrated into multiple professional society guidelines and recommendations.”

These drugs should not be confused with the wildly popular medications known as glucagon-like peptide-1 (GLP1) agonists, which include medications such as semaglutide (Ozempic and Wegovy). These drugs are generally administered via injection — unlike the oral SGLT2 inhibitors — and they’re variously indicated for type 2 diabetes and obesity.

Dr. Yokose highlighted research findings about the drugs in gout. A 2020 study, for example, tracked 295,907 US adults with type 2 diabetes who received a new prescription for an SGLT2 inhibitor or GLP1 agonist during 2013-2017. Those in the SGLT2 inhibitor group had a 36% lower risk of newly diagnosed gout (hazard ratio [HR], 0.64; 95% CI, 0.57-0.72), the researchers reported.

A similar study, a 2021 report from Taiwan, also linked SGLT2 inhibitors to improvement in gout incidence vs. dipeptidyl peptidase 4 (DPP4) inhibitors, diabetes drugs that are not linked to lower serum urate levels. In an adjusted analysis, the risk of gout was 11% lower in the SGLT2 inhibitor group (adjusted HR, 0.86; 95% CI, 0.78-0.95).

What about recurrent gout? In a 2023 study, Dr. Yokose and colleagues tracked patients with type 2 diabetes who began SGLT2 inhibitors or DPP4 inhibitors. Over the period from 2013 to 2017, those who took SGLT2 inhibitors were less likely to have gout flares (rate ratio [RR], 0.66; 95% CI, 0.57-0.75) and gout-primary emergency department visits/hospitalizations (RR, 0.52; 95% CI, 0.32-0.84).

“This finding requires further replication in other populations and compared to other drugs,” Dr. Yokose cautioned.

Another 2023 study analyzed UK data and reached similar results regarding risk of recurrent gout.

Lower Urate Levels and Less Inflammation Could Be Key

How might SGLT2 inhibitors reduce the risk of gout? Multiple studies have linked the drugs to lower serum urate levels, Dr. Yokose said, but researchers often excluded patients with gout.

For a small new study presented at the 2023 annual meeting of the American College of Rheumatology but not yet published, Dr. Yokose and colleagues reported that patients with gout who began SGLT2 inhibitors had lower urate levels than those who began a sulfonylurea, another second-line agent for type 2 diabetes. During the study period, up to 3 months before and after initiation, 43.5% of patients in the SGLT2 inhibitor group reached a target serum urate of < 6 mg/dL vs. 4.2% of sulfonylurea initiators.

“The magnitude of this reduction, while not as large as what can be achieved with appropriately titrated urate-lowering therapy such as allopurinol or febuxostat, is also not negligible. It’s believed to be between 1.5-2.0 mg/dL among patients with gout,” Dr. Yokose said. “Also, SGLT2 inhibitors are purported to have some anti-inflammatory effects that may target the same pathways responsible for the profound inflammation associated with acute gout flares. However, both the exact mechanisms underlying the serum urate-lowering and anti-inflammatory effects of SGLT2 [inhibitors] require further research and clarification.”

Moving forward, she said, “I would love to see some prospective studies of SGLT2 inhibitor use among patients with gout, looking at serum urate and clinical gout endpoints, as well as biomarkers to understand better the beneficial effects of SGLT2 inhibitors as it pertains to patients with gout.”

In Lupus, Findings Are More Mixed

Studies of SGLT2 inhibitors have excluded patients with lupus, limiting insight into their benefits in that specific population, said Dr. Jorge of Massachusetts General Hospital and Harvard Medical School. However, “one small phase I/II trial showed an acceptable safety profile of dapagliflozin add-on therapy in adult patients with SLE,” she said.

Her team is working to expand understanding about the drugs in people with lupus. At the 2023 ACR annual meeting, she presented the findings of a study that tracked patients with SLE who took SGLT2 inhibitors (n = 426, including 154 with lupus nephritis) or DPP4 inhibitors (n = 865, including 270 with lupus nephritis). Patients who took SGLT2 inhibitors had lower risks of major adverse cardiac events (HR, 0.69; 95% CI, 0.48-0.99) and renal progression (HR, 0.71; 95% CI, 0.51-0.98).

“Our results are promising, but the majority of patient with lupus who had received SGLT2 inhibitors also had the comorbidity of type 2 diabetes as a separate indication for SGLT2 inhibitor use,” Dr. Jorge said. “We still need to study the impact of SGLT2 inhibitors in patients with SLE and lupus nephritis who do not have a separate indication for the medication.”

Dr. Jorge added that “we do not yet know the ideal time to initiate SGLT2 inhibitors in the treatment of lupus nephritis. Specifically, it is not yet known whether these medications should be used in patients with persistent proteinuria due to damage from lupus nephritis or whether there is also a role to start these medications in patients with active lupus nephritis who are undergoing induction immunosuppression regimens.”

However, another study released at the 2023 ACR annual meeting suggested that SGLT2 inhibitors may not have a beneficial effect in lupus nephritis: “We observed a reduction in decline in eGFR [estimated glomerular filtration rate] after starting SGLT2 inhibitors; however, this reduction was not statistically significant … early experience suggested marginal benefit of SGLT2 inhibitors in SLE,” researchers from Johns Hopkins University, and the University of Maryland, Baltimore, reported.

“My cohort is not showing miracles from SGLT2 inhibitors,” study lead author Michelle Petri, MD, MPH, of Johns Hopkins, said in an interview.

Still, new European Alliance of Associations for Rheumatology recommendations for SLE now advise to consider the use of the drugs in patients with lupus nephritis who have reduced eGFR. Meanwhile, “the American College of Rheumatology is currently developing new treatment guidelines for SLE and for lupus nephritis, and SGLT2 inhibitors will likely be a topic of consideration,” Dr. Jorge added.

As for mechanism, Dr. Jorge said it’s not clear how the drugs may affect lupus. “It’s proposed that they have benefits in hemodynamic effects as well as potentially anti-inflammatory effects. The hemodynamic effects, including reducing intraglomerular hyperfiltration and reducing blood pressure, likely have similar benefits in patients with chronic kidney disease due to diabetic nephropathy or due to lupus nephritis with damage/scarring and persistent proteinuria. Patients with SLE and other chronic, systemic rheumatic diseases such as ANCA [antineutrophilic cytoplasmic antibody]-associated vasculitis also develop kidney disease and cardiovascular events mediated by inflammatory processes.”
 

Side Effects and Cost: Where Do They Fit In?

According to Dr. Yokose, SGLT2 inhibitors “are generally quite well-tolerated, and very serious adverse effects are rare.” Side effects include disrupted urination, increased thirst, genital infections, flu-like symptoms, and swelling.

Urinary-related problems are understandable “because these drugs cause the kidneys to pass more glucose into the urine,” University of Hong Kong cardiac specialist Bernard Cheung, MBBCh, PhD, who has studied SGLT2 inhibitors, said in an interview.

In Dr. Yokose’s 2023 study of SGLT2 inhibitors in recurrent gout, patients who took the drugs were 2.15 times more likely than the comparison group to have genital infections (hazard ratio, 2.15; 95% CI, 1.39-3.30). This finding “was what we’d expect,” she said.

She added that genital infection rates were higher among patients with diabetes, women, and uncircumcised men. “Fortunately, most experienced just a single mild episode that can readily be treated with topical therapy. There does not appear to be an increased risk of urinary tract infections.”

Dr. Cheung added that “doctors should be aware of a rare adverse effect called euglycemic ketoacidosis, in which the patient has increased ketones in the blood causing it to be more acidic than normal, but the blood glucose remains within the normal range.”

As for cost, goodrx.com reports that several SGLT2 inhibitors run about $550-$683 per month, making them expensive but still cheaper than GLP-1 agonists, which can cost $1,000 or more per month. Unlike the most popular GLP-1 agonists such as Ozempic, none of the SGLT2 inhibitors are in short supply, according to the American Society of Health-System Pharmacists.

“If someone with gout already has a cardiovascular-kidney-metabolic indication for SGLT2 inhibitors and also stands to benefit in terms of lowering serum urate and risk of recurrent gout flares, there is potential for high benefit relative to cost,” Dr. Yokose said.

She added: “It is well-documented that current gout care is suboptimal, and many patients end up in the emergency room or hospitalized for gout, which in and of itself is quite costly both for the patient and the health care system. Therefore, streamlining or integrating gout and comorbidity care with SGLT2 inhibitors could potentially be quite beneficial for patients with gout.”

In regard to lupus, “many patients with lupus undergo multiple hospitalizations related to their disease, which is a source of high health care costs,” Dr. Jorge said. “Additionally, chronic kidney disease and cardiovascular disease are major causes of disability and premature mortality. Further studies will be needed to better understand whether benefits of SGLT2 inhibitors may outweigh the costs of treatment.”

As for prescribing the drugs in lupus now, Dr. Jorge said they can be an option in lupus nephritis. “There is not a clear consensus of the ideal timing to initiate SGLT2 inhibitors — e.g., degree of proteinuria or eGFR range,” she said. “However, it is less controversial that SGLT2 inhibitors should be considered in particular for patients with lupus nephritis with ongoing proteinuria despite adequate treatment with conventional therapies.”

As for gout, Dr. Yokose isn’t ready to prescribe the drugs to patients who don’t have comorbidities that can be treated by the medications. However, she noted that those patients are rare.

“If I see a patient with gout with one or more of these comorbidities, and I see that they are not already on an SGLT2 inhibitor, I definitely take the time to talk to the patient about this exciting class of drugs and will consult with their other physicians about getting them started on an SGLT2 inhibitor.”

Dr. Yokose, Dr. Petri, and Dr. Cheung have no relevant disclosures. Dr. Jorge disclosed serving as a site investigator for SLE clinical trials funded by Bristol-Myers Squibb and Cabaletta Bio; the trials are not related to SGLT2 inhibitors.

Over just a decade, sodium-glucose cotransporter-2 (SGLT2) inhibitors have revolutionized the second-line treatment of type 2 diabetes by improving the control of blood sugar, and they’re also being used to treat heart failure and chronic kidney disease. Now, there’s growing evidence that the medications have the potential to play a role in the treatment of a variety of rheumatologic diseases — gout, systemic lupus erythematosus (SLE), and lupus nephritis.

“I suspect that SGLT2 inhibitors may have a role in multiple rheumatic diseases,” said rheumatologist April Jorge, MD, of Harvard Medical School and Massachusetts General Hospital, Boston.

Jorge_April_MA_2_web.jpg

In gout, for example, “SGLT2 inhibitors hold great promise as a multipurpose treatment option,” said rheumatologist Chio Yokose, MD, MSc, also of Harvard Medical School and Massachusetts General Hospital. Both Dr. Jorge and Dr. Yokose spoke at recent medical conferences and in interviews about the potential value of the drugs in rheumatology.
 

There’s a big caveat. For the moment, SGLT2 inhibitors aren’t cleared for use in the treatment of rheumatologic conditions, and neither physician is ready to recommend prescribing them off-label outside of their FDA-approved indications.

But studies could pave the way toward more approved uses in rheumatology. And there’s good news for now: Many rheumatology patients may already be eligible to take the drugs because of other medical conditions. In gout, for example, “sizable proportions of patients have comorbidities for which they are already indicated,” Dr. Yokose said.
 

Research Hints at Gout-Busting Potential

The first SGLT2 inhibitor canagliflozin (Invokana), received FDA approval in 2013, followed by dapagliflozin (Farxiga), empagliflozin (Jardiance), ertugliflozin (Steglatro), and bexagliflozin (Brenzavvy). The drugs “lower blood sugar by causing the kidneys to remove sugar from the body through urine,” reports the National Kidney Foundation, and they “help to protect the kidneys and heart in people with CKD [chronic kidney disease].”

Yokose_Chio_MA_web.jpg

As Dr. Yokose noted in a presentation at the 2023 Gout Hyperuricemia and Crystal Associated Disease Network research symposium, SGLT2 inhibitors “have really become blockbuster drugs, and they’ve now been integrated into multiple professional society guidelines and recommendations.”

These drugs should not be confused with the wildly popular medications known as glucagon-like peptide-1 (GLP1) agonists, which include medications such as semaglutide (Ozempic and Wegovy). These drugs are generally administered via injection — unlike the oral SGLT2 inhibitors — and they’re variously indicated for type 2 diabetes and obesity.

Dr. Yokose highlighted research findings about the drugs in gout. A 2020 study, for example, tracked 295,907 US adults with type 2 diabetes who received a new prescription for an SGLT2 inhibitor or GLP1 agonist during 2013-2017. Those in the SGLT2 inhibitor group had a 36% lower risk of newly diagnosed gout (hazard ratio [HR], 0.64; 95% CI, 0.57-0.72), the researchers reported.

A similar study, a 2021 report from Taiwan, also linked SGLT2 inhibitors to improvement in gout incidence vs. dipeptidyl peptidase 4 (DPP4) inhibitors, diabetes drugs that are not linked to lower serum urate levels. In an adjusted analysis, the risk of gout was 11% lower in the SGLT2 inhibitor group (adjusted HR, 0.86; 95% CI, 0.78-0.95).

What about recurrent gout? In a 2023 study, Dr. Yokose and colleagues tracked patients with type 2 diabetes who began SGLT2 inhibitors or DPP4 inhibitors. Over the period from 2013 to 2017, those who took SGLT2 inhibitors were less likely to have gout flares (rate ratio [RR], 0.66; 95% CI, 0.57-0.75) and gout-primary emergency department visits/hospitalizations (RR, 0.52; 95% CI, 0.32-0.84).

“This finding requires further replication in other populations and compared to other drugs,” Dr. Yokose cautioned.

Another 2023 study analyzed UK data and reached similar results regarding risk of recurrent gout.

Lower Urate Levels and Less Inflammation Could Be Key

How might SGLT2 inhibitors reduce the risk of gout? Multiple studies have linked the drugs to lower serum urate levels, Dr. Yokose said, but researchers often excluded patients with gout.

For a small new study presented at the 2023 annual meeting of the American College of Rheumatology but not yet published, Dr. Yokose and colleagues reported that patients with gout who began SGLT2 inhibitors had lower urate levels than those who began a sulfonylurea, another second-line agent for type 2 diabetes. During the study period, up to 3 months before and after initiation, 43.5% of patients in the SGLT2 inhibitor group reached a target serum urate of < 6 mg/dL vs. 4.2% of sulfonylurea initiators.

“The magnitude of this reduction, while not as large as what can be achieved with appropriately titrated urate-lowering therapy such as allopurinol or febuxostat, is also not negligible. It’s believed to be between 1.5-2.0 mg/dL among patients with gout,” Dr. Yokose said. “Also, SGLT2 inhibitors are purported to have some anti-inflammatory effects that may target the same pathways responsible for the profound inflammation associated with acute gout flares. However, both the exact mechanisms underlying the serum urate-lowering and anti-inflammatory effects of SGLT2 [inhibitors] require further research and clarification.”

Moving forward, she said, “I would love to see some prospective studies of SGLT2 inhibitor use among patients with gout, looking at serum urate and clinical gout endpoints, as well as biomarkers to understand better the beneficial effects of SGLT2 inhibitors as it pertains to patients with gout.”

In Lupus, Findings Are More Mixed

Studies of SGLT2 inhibitors have excluded patients with lupus, limiting insight into their benefits in that specific population, said Dr. Jorge of Massachusetts General Hospital and Harvard Medical School. However, “one small phase I/II trial showed an acceptable safety profile of dapagliflozin add-on therapy in adult patients with SLE,” she said.

Her team is working to expand understanding about the drugs in people with lupus. At the 2023 ACR annual meeting, she presented the findings of a study that tracked patients with SLE who took SGLT2 inhibitors (n = 426, including 154 with lupus nephritis) or DPP4 inhibitors (n = 865, including 270 with lupus nephritis). Patients who took SGLT2 inhibitors had lower risks of major adverse cardiac events (HR, 0.69; 95% CI, 0.48-0.99) and renal progression (HR, 0.71; 95% CI, 0.51-0.98).

“Our results are promising, but the majority of patient with lupus who had received SGLT2 inhibitors also had the comorbidity of type 2 diabetes as a separate indication for SGLT2 inhibitor use,” Dr. Jorge said. “We still need to study the impact of SGLT2 inhibitors in patients with SLE and lupus nephritis who do not have a separate indication for the medication.”

Dr. Jorge added that “we do not yet know the ideal time to initiate SGLT2 inhibitors in the treatment of lupus nephritis. Specifically, it is not yet known whether these medications should be used in patients with persistent proteinuria due to damage from lupus nephritis or whether there is also a role to start these medications in patients with active lupus nephritis who are undergoing induction immunosuppression regimens.”

However, another study released at the 2023 ACR annual meeting suggested that SGLT2 inhibitors may not have a beneficial effect in lupus nephritis: “We observed a reduction in decline in eGFR [estimated glomerular filtration rate] after starting SGLT2 inhibitors; however, this reduction was not statistically significant … early experience suggested marginal benefit of SGLT2 inhibitors in SLE,” researchers from Johns Hopkins University, and the University of Maryland, Baltimore, reported.

“My cohort is not showing miracles from SGLT2 inhibitors,” study lead author Michelle Petri, MD, MPH, of Johns Hopkins, said in an interview.

Still, new European Alliance of Associations for Rheumatology recommendations for SLE now advise to consider the use of the drugs in patients with lupus nephritis who have reduced eGFR. Meanwhile, “the American College of Rheumatology is currently developing new treatment guidelines for SLE and for lupus nephritis, and SGLT2 inhibitors will likely be a topic of consideration,” Dr. Jorge added.

As for mechanism, Dr. Jorge said it’s not clear how the drugs may affect lupus. “It’s proposed that they have benefits in hemodynamic effects as well as potentially anti-inflammatory effects. The hemodynamic effects, including reducing intraglomerular hyperfiltration and reducing blood pressure, likely have similar benefits in patients with chronic kidney disease due to diabetic nephropathy or due to lupus nephritis with damage/scarring and persistent proteinuria. Patients with SLE and other chronic, systemic rheumatic diseases such as ANCA [antineutrophilic cytoplasmic antibody]-associated vasculitis also develop kidney disease and cardiovascular events mediated by inflammatory processes.”
 

Side Effects and Cost: Where Do They Fit In?

According to Dr. Yokose, SGLT2 inhibitors “are generally quite well-tolerated, and very serious adverse effects are rare.” Side effects include disrupted urination, increased thirst, genital infections, flu-like symptoms, and swelling.

Urinary-related problems are understandable “because these drugs cause the kidneys to pass more glucose into the urine,” University of Hong Kong cardiac specialist Bernard Cheung, MBBCh, PhD, who has studied SGLT2 inhibitors, said in an interview.

In Dr. Yokose’s 2023 study of SGLT2 inhibitors in recurrent gout, patients who took the drugs were 2.15 times more likely than the comparison group to have genital infections (hazard ratio, 2.15; 95% CI, 1.39-3.30). This finding “was what we’d expect,” she said.

She added that genital infection rates were higher among patients with diabetes, women, and uncircumcised men. “Fortunately, most experienced just a single mild episode that can readily be treated with topical therapy. There does not appear to be an increased risk of urinary tract infections.”

Dr. Cheung added that “doctors should be aware of a rare adverse effect called euglycemic ketoacidosis, in which the patient has increased ketones in the blood causing it to be more acidic than normal, but the blood glucose remains within the normal range.”

As for cost, goodrx.com reports that several SGLT2 inhibitors run about $550-$683 per month, making them expensive but still cheaper than GLP-1 agonists, which can cost $1,000 or more per month. Unlike the most popular GLP-1 agonists such as Ozempic, none of the SGLT2 inhibitors are in short supply, according to the American Society of Health-System Pharmacists.

“If someone with gout already has a cardiovascular-kidney-metabolic indication for SGLT2 inhibitors and also stands to benefit in terms of lowering serum urate and risk of recurrent gout flares, there is potential for high benefit relative to cost,” Dr. Yokose said.

She added: “It is well-documented that current gout care is suboptimal, and many patients end up in the emergency room or hospitalized for gout, which in and of itself is quite costly both for the patient and the health care system. Therefore, streamlining or integrating gout and comorbidity care with SGLT2 inhibitors could potentially be quite beneficial for patients with gout.”

In regard to lupus, “many patients with lupus undergo multiple hospitalizations related to their disease, which is a source of high health care costs,” Dr. Jorge said. “Additionally, chronic kidney disease and cardiovascular disease are major causes of disability and premature mortality. Further studies will be needed to better understand whether benefits of SGLT2 inhibitors may outweigh the costs of treatment.”

As for prescribing the drugs in lupus now, Dr. Jorge said they can be an option in lupus nephritis. “There is not a clear consensus of the ideal timing to initiate SGLT2 inhibitors — e.g., degree of proteinuria or eGFR range,” she said. “However, it is less controversial that SGLT2 inhibitors should be considered in particular for patients with lupus nephritis with ongoing proteinuria despite adequate treatment with conventional therapies.”

As for gout, Dr. Yokose isn’t ready to prescribe the drugs to patients who don’t have comorbidities that can be treated by the medications. However, she noted that those patients are rare.

“If I see a patient with gout with one or more of these comorbidities, and I see that they are not already on an SGLT2 inhibitor, I definitely take the time to talk to the patient about this exciting class of drugs and will consult with their other physicians about getting them started on an SGLT2 inhibitor.”

Dr. Yokose, Dr. Petri, and Dr. Cheung have no relevant disclosures. Dr. Jorge disclosed serving as a site investigator for SLE clinical trials funded by Bristol-Myers Squibb and Cabaletta Bio; the trials are not related to SGLT2 inhibitors.

Over just a decade, sodium-glucose cotransporter-2 (SGLT2) inhibitors have revolutionized the second-line treatment of type 2 diabetes by improving the control of blood sugar, and they’re also being used to treat heart failure and chronic kidney disease. Now, there’s growing evidence that the medications have the potential to play a role in the treatment of a variety of rheumatologic diseases — gout, systemic lupus erythematosus (SLE), and lupus nephritis.

“I suspect that SGLT2 inhibitors may have a role in multiple rheumatic diseases,” said rheumatologist April Jorge, MD, of Harvard Medical School and Massachusetts General Hospital, Boston.

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In gout, for example, “SGLT2 inhibitors hold great promise as a multipurpose treatment option,” said rheumatologist Chio Yokose, MD, MSc, also of Harvard Medical School and Massachusetts General Hospital. Both Dr. Jorge and Dr. Yokose spoke at recent medical conferences and in interviews about the potential value of the drugs in rheumatology.
 

There’s a big caveat. For the moment, SGLT2 inhibitors aren’t cleared for use in the treatment of rheumatologic conditions, and neither physician is ready to recommend prescribing them off-label outside of their FDA-approved indications.

But studies could pave the way toward more approved uses in rheumatology. And there’s good news for now: Many rheumatology patients may already be eligible to take the drugs because of other medical conditions. In gout, for example, “sizable proportions of patients have comorbidities for which they are already indicated,” Dr. Yokose said.
 

Research Hints at Gout-Busting Potential

The first SGLT2 inhibitor canagliflozin (Invokana), received FDA approval in 2013, followed by dapagliflozin (Farxiga), empagliflozin (Jardiance), ertugliflozin (Steglatro), and bexagliflozin (Brenzavvy). The drugs “lower blood sugar by causing the kidneys to remove sugar from the body through urine,” reports the National Kidney Foundation, and they “help to protect the kidneys and heart in people with CKD [chronic kidney disease].”

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As Dr. Yokose noted in a presentation at the 2023 Gout Hyperuricemia and Crystal Associated Disease Network research symposium, SGLT2 inhibitors “have really become blockbuster drugs, and they’ve now been integrated into multiple professional society guidelines and recommendations.”

These drugs should not be confused with the wildly popular medications known as glucagon-like peptide-1 (GLP1) agonists, which include medications such as semaglutide (Ozempic and Wegovy). These drugs are generally administered via injection — unlike the oral SGLT2 inhibitors — and they’re variously indicated for type 2 diabetes and obesity.

Dr. Yokose highlighted research findings about the drugs in gout. A 2020 study, for example, tracked 295,907 US adults with type 2 diabetes who received a new prescription for an SGLT2 inhibitor or GLP1 agonist during 2013-2017. Those in the SGLT2 inhibitor group had a 36% lower risk of newly diagnosed gout (hazard ratio [HR], 0.64; 95% CI, 0.57-0.72), the researchers reported.

A similar study, a 2021 report from Taiwan, also linked SGLT2 inhibitors to improvement in gout incidence vs. dipeptidyl peptidase 4 (DPP4) inhibitors, diabetes drugs that are not linked to lower serum urate levels. In an adjusted analysis, the risk of gout was 11% lower in the SGLT2 inhibitor group (adjusted HR, 0.86; 95% CI, 0.78-0.95).

What about recurrent gout? In a 2023 study, Dr. Yokose and colleagues tracked patients with type 2 diabetes who began SGLT2 inhibitors or DPP4 inhibitors. Over the period from 2013 to 2017, those who took SGLT2 inhibitors were less likely to have gout flares (rate ratio [RR], 0.66; 95% CI, 0.57-0.75) and gout-primary emergency department visits/hospitalizations (RR, 0.52; 95% CI, 0.32-0.84).

“This finding requires further replication in other populations and compared to other drugs,” Dr. Yokose cautioned.

Another 2023 study analyzed UK data and reached similar results regarding risk of recurrent gout.

Lower Urate Levels and Less Inflammation Could Be Key

How might SGLT2 inhibitors reduce the risk of gout? Multiple studies have linked the drugs to lower serum urate levels, Dr. Yokose said, but researchers often excluded patients with gout.

For a small new study presented at the 2023 annual meeting of the American College of Rheumatology but not yet published, Dr. Yokose and colleagues reported that patients with gout who began SGLT2 inhibitors had lower urate levels than those who began a sulfonylurea, another second-line agent for type 2 diabetes. During the study period, up to 3 months before and after initiation, 43.5% of patients in the SGLT2 inhibitor group reached a target serum urate of < 6 mg/dL vs. 4.2% of sulfonylurea initiators.

“The magnitude of this reduction, while not as large as what can be achieved with appropriately titrated urate-lowering therapy such as allopurinol or febuxostat, is also not negligible. It’s believed to be between 1.5-2.0 mg/dL among patients with gout,” Dr. Yokose said. “Also, SGLT2 inhibitors are purported to have some anti-inflammatory effects that may target the same pathways responsible for the profound inflammation associated with acute gout flares. However, both the exact mechanisms underlying the serum urate-lowering and anti-inflammatory effects of SGLT2 [inhibitors] require further research and clarification.”

Moving forward, she said, “I would love to see some prospective studies of SGLT2 inhibitor use among patients with gout, looking at serum urate and clinical gout endpoints, as well as biomarkers to understand better the beneficial effects of SGLT2 inhibitors as it pertains to patients with gout.”

In Lupus, Findings Are More Mixed

Studies of SGLT2 inhibitors have excluded patients with lupus, limiting insight into their benefits in that specific population, said Dr. Jorge of Massachusetts General Hospital and Harvard Medical School. However, “one small phase I/II trial showed an acceptable safety profile of dapagliflozin add-on therapy in adult patients with SLE,” she said.

Her team is working to expand understanding about the drugs in people with lupus. At the 2023 ACR annual meeting, she presented the findings of a study that tracked patients with SLE who took SGLT2 inhibitors (n = 426, including 154 with lupus nephritis) or DPP4 inhibitors (n = 865, including 270 with lupus nephritis). Patients who took SGLT2 inhibitors had lower risks of major adverse cardiac events (HR, 0.69; 95% CI, 0.48-0.99) and renal progression (HR, 0.71; 95% CI, 0.51-0.98).

“Our results are promising, but the majority of patient with lupus who had received SGLT2 inhibitors also had the comorbidity of type 2 diabetes as a separate indication for SGLT2 inhibitor use,” Dr. Jorge said. “We still need to study the impact of SGLT2 inhibitors in patients with SLE and lupus nephritis who do not have a separate indication for the medication.”

Dr. Jorge added that “we do not yet know the ideal time to initiate SGLT2 inhibitors in the treatment of lupus nephritis. Specifically, it is not yet known whether these medications should be used in patients with persistent proteinuria due to damage from lupus nephritis or whether there is also a role to start these medications in patients with active lupus nephritis who are undergoing induction immunosuppression regimens.”

However, another study released at the 2023 ACR annual meeting suggested that SGLT2 inhibitors may not have a beneficial effect in lupus nephritis: “We observed a reduction in decline in eGFR [estimated glomerular filtration rate] after starting SGLT2 inhibitors; however, this reduction was not statistically significant … early experience suggested marginal benefit of SGLT2 inhibitors in SLE,” researchers from Johns Hopkins University, and the University of Maryland, Baltimore, reported.

“My cohort is not showing miracles from SGLT2 inhibitors,” study lead author Michelle Petri, MD, MPH, of Johns Hopkins, said in an interview.

Still, new European Alliance of Associations for Rheumatology recommendations for SLE now advise to consider the use of the drugs in patients with lupus nephritis who have reduced eGFR. Meanwhile, “the American College of Rheumatology is currently developing new treatment guidelines for SLE and for lupus nephritis, and SGLT2 inhibitors will likely be a topic of consideration,” Dr. Jorge added.

As for mechanism, Dr. Jorge said it’s not clear how the drugs may affect lupus. “It’s proposed that they have benefits in hemodynamic effects as well as potentially anti-inflammatory effects. The hemodynamic effects, including reducing intraglomerular hyperfiltration and reducing blood pressure, likely have similar benefits in patients with chronic kidney disease due to diabetic nephropathy or due to lupus nephritis with damage/scarring and persistent proteinuria. Patients with SLE and other chronic, systemic rheumatic diseases such as ANCA [antineutrophilic cytoplasmic antibody]-associated vasculitis also develop kidney disease and cardiovascular events mediated by inflammatory processes.”
 

Side Effects and Cost: Where Do They Fit In?

According to Dr. Yokose, SGLT2 inhibitors “are generally quite well-tolerated, and very serious adverse effects are rare.” Side effects include disrupted urination, increased thirst, genital infections, flu-like symptoms, and swelling.

Urinary-related problems are understandable “because these drugs cause the kidneys to pass more glucose into the urine,” University of Hong Kong cardiac specialist Bernard Cheung, MBBCh, PhD, who has studied SGLT2 inhibitors, said in an interview.

In Dr. Yokose’s 2023 study of SGLT2 inhibitors in recurrent gout, patients who took the drugs were 2.15 times more likely than the comparison group to have genital infections (hazard ratio, 2.15; 95% CI, 1.39-3.30). This finding “was what we’d expect,” she said.

She added that genital infection rates were higher among patients with diabetes, women, and uncircumcised men. “Fortunately, most experienced just a single mild episode that can readily be treated with topical therapy. There does not appear to be an increased risk of urinary tract infections.”

Dr. Cheung added that “doctors should be aware of a rare adverse effect called euglycemic ketoacidosis, in which the patient has increased ketones in the blood causing it to be more acidic than normal, but the blood glucose remains within the normal range.”

As for cost, goodrx.com reports that several SGLT2 inhibitors run about $550-$683 per month, making them expensive but still cheaper than GLP-1 agonists, which can cost $1,000 or more per month. Unlike the most popular GLP-1 agonists such as Ozempic, none of the SGLT2 inhibitors are in short supply, according to the American Society of Health-System Pharmacists.

“If someone with gout already has a cardiovascular-kidney-metabolic indication for SGLT2 inhibitors and also stands to benefit in terms of lowering serum urate and risk of recurrent gout flares, there is potential for high benefit relative to cost,” Dr. Yokose said.

She added: “It is well-documented that current gout care is suboptimal, and many patients end up in the emergency room or hospitalized for gout, which in and of itself is quite costly both for the patient and the health care system. Therefore, streamlining or integrating gout and comorbidity care with SGLT2 inhibitors could potentially be quite beneficial for patients with gout.”

In regard to lupus, “many patients with lupus undergo multiple hospitalizations related to their disease, which is a source of high health care costs,” Dr. Jorge said. “Additionally, chronic kidney disease and cardiovascular disease are major causes of disability and premature mortality. Further studies will be needed to better understand whether benefits of SGLT2 inhibitors may outweigh the costs of treatment.”

As for prescribing the drugs in lupus now, Dr. Jorge said they can be an option in lupus nephritis. “There is not a clear consensus of the ideal timing to initiate SGLT2 inhibitors — e.g., degree of proteinuria or eGFR range,” she said. “However, it is less controversial that SGLT2 inhibitors should be considered in particular for patients with lupus nephritis with ongoing proteinuria despite adequate treatment with conventional therapies.”

As for gout, Dr. Yokose isn’t ready to prescribe the drugs to patients who don’t have comorbidities that can be treated by the medications. However, she noted that those patients are rare.

“If I see a patient with gout with one or more of these comorbidities, and I see that they are not already on an SGLT2 inhibitor, I definitely take the time to talk to the patient about this exciting class of drugs and will consult with their other physicians about getting them started on an SGLT2 inhibitor.”

Dr. Yokose, Dr. Petri, and Dr. Cheung have no relevant disclosures. Dr. Jorge disclosed serving as a site investigator for SLE clinical trials funded by Bristol-Myers Squibb and Cabaletta Bio; the trials are not related to SGLT2 inhibitors.

Use of oral amoxicillin-clavulanic acid for 5 days was noninferior to a 10-day course of treatment among children with noncomplicated febrile urinary tract infections (UTIs), according to new research.

Well-appearing children with febrile UTIs are generally treated with a 10-day course of oral antibiotics, but the effectiveness of a 5-day course has not been evaluated, wrote Giovanni Montini, MD, of the University of Milan, Milan, Italy, and colleagues.

Robert W. Frenck Jr, MD, a director of the Center for Vaccine Research at Cincinnati Children’s Hospital Medical Center, Ohio, said he was not surprised that the shorter course was sufficient to treat these cases. The antibiotic concentration in the urine often significantly exceeds the levels in the blood, he said.

Dr. Frenck, who was not involved in the study, said that he saw no real barriers to the use of a shorter course of therapy in clinical practice.

“I think both parents and the medical team would be happy to be able to use a shorter course of therapy,” he said.

In the study published in Pediatrics , researchers randomized 142 children aged 3 months to 5 years with uncomplicated febrile UTIs to 50 mg/kg/d of amoxicillin-clavulanate for either the short or standard period. The study took place at eight pediatric emergency departments in Italy between May 2020 and September 2022. All patients received prescriptions for 5 days of antibiotics, and those randomized to the standard course received a second prescription after randomization.

The primary endpoint was recurrence of the UTI within 30 days of completion of therapy. Secondary endpoints included clinical recovery at the end of treatment, adverse events related to the therapy, and signs of antibiotic resistance.

The UTI recurrence rate within 30 days of treatment completion was 2.8% in the short-course group and 14.3% in the standard group. A post hoc analysis excluding patients with vesicoureteral reflux and non–Escherichia coli UTIs further confirmed the noninferiority of short-course treatment.

“It is a bit surprising that the short-course group had fewer relapses within 30 days of discontinuing antibiotics,” Dr. Frenck said. “However, the differences may be due to small sample sizes and do not appear to be statistically significant differences in recurrence rates.”

Resolution of symptoms was similar between the short-course and standard groups (97.2% and 92.9%, respectively), and indications of antibiotic resistance were similar between the groups. No adverse events were reported in the standard group, and one case of diarrhea occurred in the short-course group.

The findings were limited by the study’s unblinded randomization, so parents were aware of the trial and were potentially sensitized to look for signs of infection. Researchers also relied on parent reports of adverse drug effects rather than through a standardized questionnaire, the researchers noted.

Dr. Frenck said a potential benefit to shortening treatment is that adherence usually increases.

“But you only want to decrease the length of a course of medicine if you can do so without compromising the effectiveness of the treatment,” Dr. Frenck said.

Dr. Frenck also noted a recent study, which demonstrated that 5 days of antibiotics had equivalent efficacy as 10 days for uncomplicated pneumonia.

“The current paper further demonstrates that shorter courses of antibiotics may be possible for other mild forms of infections.”

Looking ahead, researchers could evaluate the use of short-course antibiotics for other common infections such as otitis media, he noted.

The study was supported by the Ministry of Health, Rome, Italy, in collaboration with the Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy. The researchers report no financial conflicts. Dr. Frenck disclosed conducting clinical trials for Pfizer, Moderna, AstraZeneca, Merck, and GSK; none of those trials were for antibiotics or urinary tract infections.

A version of this article appeared on Medscape.com.

Use of oral amoxicillin-clavulanic acid for 5 days was noninferior to a 10-day course of treatment among children with noncomplicated febrile urinary tract infections (UTIs), according to new research.

Well-appearing children with febrile UTIs are generally treated with a 10-day course of oral antibiotics, but the effectiveness of a 5-day course has not been evaluated, wrote Giovanni Montini, MD, of the University of Milan, Milan, Italy, and colleagues.

Robert W. Frenck Jr, MD, a director of the Center for Vaccine Research at Cincinnati Children’s Hospital Medical Center, Ohio, said he was not surprised that the shorter course was sufficient to treat these cases. The antibiotic concentration in the urine often significantly exceeds the levels in the blood, he said.

Dr. Frenck, who was not involved in the study, said that he saw no real barriers to the use of a shorter course of therapy in clinical practice.

“I think both parents and the medical team would be happy to be able to use a shorter course of therapy,” he said.

In the study published in Pediatrics , researchers randomized 142 children aged 3 months to 5 years with uncomplicated febrile UTIs to 50 mg/kg/d of amoxicillin-clavulanate for either the short or standard period. The study took place at eight pediatric emergency departments in Italy between May 2020 and September 2022. All patients received prescriptions for 5 days of antibiotics, and those randomized to the standard course received a second prescription after randomization.

The primary endpoint was recurrence of the UTI within 30 days of completion of therapy. Secondary endpoints included clinical recovery at the end of treatment, adverse events related to the therapy, and signs of antibiotic resistance.

The UTI recurrence rate within 30 days of treatment completion was 2.8% in the short-course group and 14.3% in the standard group. A post hoc analysis excluding patients with vesicoureteral reflux and non–Escherichia coli UTIs further confirmed the noninferiority of short-course treatment.

“It is a bit surprising that the short-course group had fewer relapses within 30 days of discontinuing antibiotics,” Dr. Frenck said. “However, the differences may be due to small sample sizes and do not appear to be statistically significant differences in recurrence rates.”

Resolution of symptoms was similar between the short-course and standard groups (97.2% and 92.9%, respectively), and indications of antibiotic resistance were similar between the groups. No adverse events were reported in the standard group, and one case of diarrhea occurred in the short-course group.

The findings were limited by the study’s unblinded randomization, so parents were aware of the trial and were potentially sensitized to look for signs of infection. Researchers also relied on parent reports of adverse drug effects rather than through a standardized questionnaire, the researchers noted.

Dr. Frenck said a potential benefit to shortening treatment is that adherence usually increases.

“But you only want to decrease the length of a course of medicine if you can do so without compromising the effectiveness of the treatment,” Dr. Frenck said.

Dr. Frenck also noted a recent study, which demonstrated that 5 days of antibiotics had equivalent efficacy as 10 days for uncomplicated pneumonia.

“The current paper further demonstrates that shorter courses of antibiotics may be possible for other mild forms of infections.”

Looking ahead, researchers could evaluate the use of short-course antibiotics for other common infections such as otitis media, he noted.

The study was supported by the Ministry of Health, Rome, Italy, in collaboration with the Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy. The researchers report no financial conflicts. Dr. Frenck disclosed conducting clinical trials for Pfizer, Moderna, AstraZeneca, Merck, and GSK; none of those trials were for antibiotics or urinary tract infections.

A version of this article appeared on Medscape.com.

Use of oral amoxicillin-clavulanic acid for 5 days was noninferior to a 10-day course of treatment among children with noncomplicated febrile urinary tract infections (UTIs), according to new research.

Well-appearing children with febrile UTIs are generally treated with a 10-day course of oral antibiotics, but the effectiveness of a 5-day course has not been evaluated, wrote Giovanni Montini, MD, of the University of Milan, Milan, Italy, and colleagues.

Robert W. Frenck Jr, MD, a director of the Center for Vaccine Research at Cincinnati Children’s Hospital Medical Center, Ohio, said he was not surprised that the shorter course was sufficient to treat these cases. The antibiotic concentration in the urine often significantly exceeds the levels in the blood, he said.

Dr. Frenck, who was not involved in the study, said that he saw no real barriers to the use of a shorter course of therapy in clinical practice.

“I think both parents and the medical team would be happy to be able to use a shorter course of therapy,” he said.

In the study published in Pediatrics , researchers randomized 142 children aged 3 months to 5 years with uncomplicated febrile UTIs to 50 mg/kg/d of amoxicillin-clavulanate for either the short or standard period. The study took place at eight pediatric emergency departments in Italy between May 2020 and September 2022. All patients received prescriptions for 5 days of antibiotics, and those randomized to the standard course received a second prescription after randomization.

The primary endpoint was recurrence of the UTI within 30 days of completion of therapy. Secondary endpoints included clinical recovery at the end of treatment, adverse events related to the therapy, and signs of antibiotic resistance.

The UTI recurrence rate within 30 days of treatment completion was 2.8% in the short-course group and 14.3% in the standard group. A post hoc analysis excluding patients with vesicoureteral reflux and non–Escherichia coli UTIs further confirmed the noninferiority of short-course treatment.

“It is a bit surprising that the short-course group had fewer relapses within 30 days of discontinuing antibiotics,” Dr. Frenck said. “However, the differences may be due to small sample sizes and do not appear to be statistically significant differences in recurrence rates.”

Resolution of symptoms was similar between the short-course and standard groups (97.2% and 92.9%, respectively), and indications of antibiotic resistance were similar between the groups. No adverse events were reported in the standard group, and one case of diarrhea occurred in the short-course group.

The findings were limited by the study’s unblinded randomization, so parents were aware of the trial and were potentially sensitized to look for signs of infection. Researchers also relied on parent reports of adverse drug effects rather than through a standardized questionnaire, the researchers noted.

Dr. Frenck said a potential benefit to shortening treatment is that adherence usually increases.

“But you only want to decrease the length of a course of medicine if you can do so without compromising the effectiveness of the treatment,” Dr. Frenck said.

Dr. Frenck also noted a recent study, which demonstrated that 5 days of antibiotics had equivalent efficacy as 10 days for uncomplicated pneumonia.

“The current paper further demonstrates that shorter courses of antibiotics may be possible for other mild forms of infections.”

Looking ahead, researchers could evaluate the use of short-course antibiotics for other common infections such as otitis media, he noted.

The study was supported by the Ministry of Health, Rome, Italy, in collaboration with the Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy. The researchers report no financial conflicts. Dr. Frenck disclosed conducting clinical trials for Pfizer, Moderna, AstraZeneca, Merck, and GSK; none of those trials were for antibiotics or urinary tract infections.

A version of this article appeared on Medscape.com.

Maintaining remission in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis who have kept their autoantibodies in check after at least 2 years on rituximab therapy has proved challenging, but a team of nephrologists in Boston have reported that a longer-term strategy that uses a rise in B-cell levels as a threshold for rituximab infusions may be the better of two strategies at reducing relapse risks. 

“The bottom line is with the B-cell strategy, which is that rituximab was redosed when the B cells recovered or started to recover, we only have a 6% rate in relapses by 3 years,” senior study author John L. Niles, MD, assistant professor of medicine at the Harvard Medical School and director of the Vasculitis and Glomerulonephritis Center at Massachusetts General Hospital in Boston, Massachusetts, told Medscape Medical News.

Niles_John_L_MA_web.jpg

“Whereas in the other strategy, we were waiting for a serologic relapse and hoping we could prevent clinical relapses, but we still have about 30% rate of relapse by 3 years.”

Dr. Niles and his associates reported their findings from the MAINTANCVAS study (for MAINTenance of ANCA VASculitis) December 11, 2023, in Annals of the Rheumatic Diseases. Their single-center study compared two different treatment strategies in patients with ANCA-associated vasculitis in remission after completing at least 2 years of fixed-schedule rituximab therapy: an approach that reinfused rituximab upon B-cell repopulation, called the B-cell arm and a strategy that reinfused rituximab when serologic levels of ANCA increased significantly, which they called the ANCA arm. A total of 115 patients were randomly assigned to either arm.
 

Study Results

Median follow-up was 4.1 years from study entry. Throughout the study, 5 of 58 patients in the B-cell arm and 14 of 57 in the ANCA arm had relapses. According to Kaplan-Meier analysis, at 3 years after study entry, 4.1% of patients in the B-cell arm had a relapse vs 20.5% of patients in the ANCA arm. At 5 years, the respective relapse rates were 11.3% and 27.7%. Overall, four major relapses occurred in the B-cell arm and seven in the ANCA arm.

The COVID-19 pandemic caused the researchers to halt the study before it was fully enrolled, Dr. Niles said. The study also attributed high rates of serious adverse events (SAEs) in the B-cell arm to cases of COVID-19 in that study population. The overall number of SAEs was identical in both arms: 22 (P = .95). But the B-cell arm had six cases of COVID-19 vs one in the ANCA arm, including two deaths because of COVID-19.

The study findings provided insight into how to best individualize treatment in patients with ANCA-associated vasculitis, Dr. Niles said. “We will typically start with the B-cell strategy after 2 years, but to the extent that people have infections or hypogammaglobulinemia, we’ll start stretching a little longer on the B cells, and if the level is too high in terms of infection, we’ll stop and switch to the ANCA strategy,” he said.

He added, “Relapsers get a more strict B-cell strategy, and people with infections get much longer intervals or even switch entirely to the ANCA strategy.”

Because the study ended before it was fully enrolled, it was underpowered for subgroup analyses, Dr. Niles noted. One such potential subgroup was relapsing patients with interstitial lung disease as the primary clinical finding. “The interstitial lung disease doesn’t seem to respond as well to therapy as the other classic features of ANCA disease,” Dr. Niles said. “It’s the one part that’s the most problematic for the long run. It behaves differently, and there’s going to need to be more research on ILD. Fortunately, it’s a fairly small percentage of the total group, but it’s the most difficult part of this disease.”
 

Findings in Context

This study brings clarity on how to best manage patients with ANCA-associated vasculitis, Robert Hylland, MD, an assistant clinical professor of rheumatology at Michigan State University College of Osteopathic Medicine, told this news organization.

“Most of us have tried to discern from the literature that exists how to manage [ANCA-associated vasculitis]. There have been a number of different approaches, and they have changed over the course of time,” Dr. Hylland said. “But now this article helps us to understand how to proceed with this disease after we have induced remission. The ability to determine the validity of serology vs B-cell depletion was brought out very nicely in this article.”

Hylland_Robert_MI_web.jpg

The size of the study population was a strength of the study, Dr. Hylland said. 

He credited the study authors for providing insight into using positive myeloperoxidase (MPO)- or proteinase 3 (PR3)-ANCA readings to guide treatment for relapses. The study defined a serologic ANCA flare in the ANCA arm as a fivefold increase in MPO and a fourfold rise in PR3.

“Many of us wouldn’t have recognized that a less than fivefold increase, for example, in the MPO could be watched for a while, where most of us would have been treating that serologic flare,” Hylland said.

The study also highlighted the difficulty of evaluating a patient who has neither a positive ANCA nor a significant increase in their B-cell counts and yet still has clinical signs and symptoms of a relapse, such as with granulomatosis with polyangiitis, also known as Wegener’s granulomatosis.

“A lot of physicians tend to feel a little more relaxed when they see their patient is serologically doing well and yet, when they come in, some of the subtle symptoms of Wegener’s could be ignored if you don’t recognize that there’s a considerable number who will come to you with having had treatment and still have negative serology,” Hylland said.

The study had no specific outside funding source. Dr. Niles and Dr. Hylland report no relevant financial relationships. Two co-authors report financial relationships with pharmaceutical companies.

A version of this article appeared on Medscape.com.

Maintaining remission in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis who have kept their autoantibodies in check after at least 2 years on rituximab therapy has proved challenging, but a team of nephrologists in Boston have reported that a longer-term strategy that uses a rise in B-cell levels as a threshold for rituximab infusions may be the better of two strategies at reducing relapse risks. 

“The bottom line is with the B-cell strategy, which is that rituximab was redosed when the B cells recovered or started to recover, we only have a 6% rate in relapses by 3 years,” senior study author John L. Niles, MD, assistant professor of medicine at the Harvard Medical School and director of the Vasculitis and Glomerulonephritis Center at Massachusetts General Hospital in Boston, Massachusetts, told Medscape Medical News.

Niles_John_L_MA_web.jpg

“Whereas in the other strategy, we were waiting for a serologic relapse and hoping we could prevent clinical relapses, but we still have about 30% rate of relapse by 3 years.”

Dr. Niles and his associates reported their findings from the MAINTANCVAS study (for MAINTenance of ANCA VASculitis) December 11, 2023, in Annals of the Rheumatic Diseases. Their single-center study compared two different treatment strategies in patients with ANCA-associated vasculitis in remission after completing at least 2 years of fixed-schedule rituximab therapy: an approach that reinfused rituximab upon B-cell repopulation, called the B-cell arm and a strategy that reinfused rituximab when serologic levels of ANCA increased significantly, which they called the ANCA arm. A total of 115 patients were randomly assigned to either arm.
 

Study Results

Median follow-up was 4.1 years from study entry. Throughout the study, 5 of 58 patients in the B-cell arm and 14 of 57 in the ANCA arm had relapses. According to Kaplan-Meier analysis, at 3 years after study entry, 4.1% of patients in the B-cell arm had a relapse vs 20.5% of patients in the ANCA arm. At 5 years, the respective relapse rates were 11.3% and 27.7%. Overall, four major relapses occurred in the B-cell arm and seven in the ANCA arm.

The COVID-19 pandemic caused the researchers to halt the study before it was fully enrolled, Dr. Niles said. The study also attributed high rates of serious adverse events (SAEs) in the B-cell arm to cases of COVID-19 in that study population. The overall number of SAEs was identical in both arms: 22 (P = .95). But the B-cell arm had six cases of COVID-19 vs one in the ANCA arm, including two deaths because of COVID-19.

The study findings provided insight into how to best individualize treatment in patients with ANCA-associated vasculitis, Dr. Niles said. “We will typically start with the B-cell strategy after 2 years, but to the extent that people have infections or hypogammaglobulinemia, we’ll start stretching a little longer on the B cells, and if the level is too high in terms of infection, we’ll stop and switch to the ANCA strategy,” he said.

He added, “Relapsers get a more strict B-cell strategy, and people with infections get much longer intervals or even switch entirely to the ANCA strategy.”

Because the study ended before it was fully enrolled, it was underpowered for subgroup analyses, Dr. Niles noted. One such potential subgroup was relapsing patients with interstitial lung disease as the primary clinical finding. “The interstitial lung disease doesn’t seem to respond as well to therapy as the other classic features of ANCA disease,” Dr. Niles said. “It’s the one part that’s the most problematic for the long run. It behaves differently, and there’s going to need to be more research on ILD. Fortunately, it’s a fairly small percentage of the total group, but it’s the most difficult part of this disease.”
 

Findings in Context

This study brings clarity on how to best manage patients with ANCA-associated vasculitis, Robert Hylland, MD, an assistant clinical professor of rheumatology at Michigan State University College of Osteopathic Medicine, told this news organization.

“Most of us have tried to discern from the literature that exists how to manage [ANCA-associated vasculitis]. There have been a number of different approaches, and they have changed over the course of time,” Dr. Hylland said. “But now this article helps us to understand how to proceed with this disease after we have induced remission. The ability to determine the validity of serology vs B-cell depletion was brought out very nicely in this article.”

Hylland_Robert_MI_web.jpg

The size of the study population was a strength of the study, Dr. Hylland said. 

He credited the study authors for providing insight into using positive myeloperoxidase (MPO)- or proteinase 3 (PR3)-ANCA readings to guide treatment for relapses. The study defined a serologic ANCA flare in the ANCA arm as a fivefold increase in MPO and a fourfold rise in PR3.

“Many of us wouldn’t have recognized that a less than fivefold increase, for example, in the MPO could be watched for a while, where most of us would have been treating that serologic flare,” Hylland said.

The study also highlighted the difficulty of evaluating a patient who has neither a positive ANCA nor a significant increase in their B-cell counts and yet still has clinical signs and symptoms of a relapse, such as with granulomatosis with polyangiitis, also known as Wegener’s granulomatosis.

“A lot of physicians tend to feel a little more relaxed when they see their patient is serologically doing well and yet, when they come in, some of the subtle symptoms of Wegener’s could be ignored if you don’t recognize that there’s a considerable number who will come to you with having had treatment and still have negative serology,” Hylland said.

The study had no specific outside funding source. Dr. Niles and Dr. Hylland report no relevant financial relationships. Two co-authors report financial relationships with pharmaceutical companies.

A version of this article appeared on Medscape.com.

Maintaining remission in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis who have kept their autoantibodies in check after at least 2 years on rituximab therapy has proved challenging, but a team of nephrologists in Boston have reported that a longer-term strategy that uses a rise in B-cell levels as a threshold for rituximab infusions may be the better of two strategies at reducing relapse risks. 

“The bottom line is with the B-cell strategy, which is that rituximab was redosed when the B cells recovered or started to recover, we only have a 6% rate in relapses by 3 years,” senior study author John L. Niles, MD, assistant professor of medicine at the Harvard Medical School and director of the Vasculitis and Glomerulonephritis Center at Massachusetts General Hospital in Boston, Massachusetts, told Medscape Medical News.

Niles_John_L_MA_web.jpg

“Whereas in the other strategy, we were waiting for a serologic relapse and hoping we could prevent clinical relapses, but we still have about 30% rate of relapse by 3 years.”

Dr. Niles and his associates reported their findings from the MAINTANCVAS study (for MAINTenance of ANCA VASculitis) December 11, 2023, in Annals of the Rheumatic Diseases. Their single-center study compared two different treatment strategies in patients with ANCA-associated vasculitis in remission after completing at least 2 years of fixed-schedule rituximab therapy: an approach that reinfused rituximab upon B-cell repopulation, called the B-cell arm and a strategy that reinfused rituximab when serologic levels of ANCA increased significantly, which they called the ANCA arm. A total of 115 patients were randomly assigned to either arm.
 

Study Results

Median follow-up was 4.1 years from study entry. Throughout the study, 5 of 58 patients in the B-cell arm and 14 of 57 in the ANCA arm had relapses. According to Kaplan-Meier analysis, at 3 years after study entry, 4.1% of patients in the B-cell arm had a relapse vs 20.5% of patients in the ANCA arm. At 5 years, the respective relapse rates were 11.3% and 27.7%. Overall, four major relapses occurred in the B-cell arm and seven in the ANCA arm.

The COVID-19 pandemic caused the researchers to halt the study before it was fully enrolled, Dr. Niles said. The study also attributed high rates of serious adverse events (SAEs) in the B-cell arm to cases of COVID-19 in that study population. The overall number of SAEs was identical in both arms: 22 (P = .95). But the B-cell arm had six cases of COVID-19 vs one in the ANCA arm, including two deaths because of COVID-19.

The study findings provided insight into how to best individualize treatment in patients with ANCA-associated vasculitis, Dr. Niles said. “We will typically start with the B-cell strategy after 2 years, but to the extent that people have infections or hypogammaglobulinemia, we’ll start stretching a little longer on the B cells, and if the level is too high in terms of infection, we’ll stop and switch to the ANCA strategy,” he said.

He added, “Relapsers get a more strict B-cell strategy, and people with infections get much longer intervals or even switch entirely to the ANCA strategy.”

Because the study ended before it was fully enrolled, it was underpowered for subgroup analyses, Dr. Niles noted. One such potential subgroup was relapsing patients with interstitial lung disease as the primary clinical finding. “The interstitial lung disease doesn’t seem to respond as well to therapy as the other classic features of ANCA disease,” Dr. Niles said. “It’s the one part that’s the most problematic for the long run. It behaves differently, and there’s going to need to be more research on ILD. Fortunately, it’s a fairly small percentage of the total group, but it’s the most difficult part of this disease.”
 

Findings in Context

This study brings clarity on how to best manage patients with ANCA-associated vasculitis, Robert Hylland, MD, an assistant clinical professor of rheumatology at Michigan State University College of Osteopathic Medicine, told this news organization.

“Most of us have tried to discern from the literature that exists how to manage [ANCA-associated vasculitis]. There have been a number of different approaches, and they have changed over the course of time,” Dr. Hylland said. “But now this article helps us to understand how to proceed with this disease after we have induced remission. The ability to determine the validity of serology vs B-cell depletion was brought out very nicely in this article.”

Hylland_Robert_MI_web.jpg

The size of the study population was a strength of the study, Dr. Hylland said. 

He credited the study authors for providing insight into using positive myeloperoxidase (MPO)- or proteinase 3 (PR3)-ANCA readings to guide treatment for relapses. The study defined a serologic ANCA flare in the ANCA arm as a fivefold increase in MPO and a fourfold rise in PR3.

“Many of us wouldn’t have recognized that a less than fivefold increase, for example, in the MPO could be watched for a while, where most of us would have been treating that serologic flare,” Hylland said.

The study also highlighted the difficulty of evaluating a patient who has neither a positive ANCA nor a significant increase in their B-cell counts and yet still has clinical signs and symptoms of a relapse, such as with granulomatosis with polyangiitis, also known as Wegener’s granulomatosis.

“A lot of physicians tend to feel a little more relaxed when they see their patient is serologically doing well and yet, when they come in, some of the subtle symptoms of Wegener’s could be ignored if you don’t recognize that there’s a considerable number who will come to you with having had treatment and still have negative serology,” Hylland said.

The study had no specific outside funding source. Dr. Niles and Dr. Hylland report no relevant financial relationships. Two co-authors report financial relationships with pharmaceutical companies.

A version of this article appeared on Medscape.com.

TOPLINE:

Gut and urinary microbiota alterations appear to play key roles in the development of kidney stones, suggesting that avoidance of modulators such as a poor diet and antibiotic use could help prevent kidney stone recurrence. 

Kidney stones are commonly formed by calcium oxalate produced by the body, but the findings suggest that in efforts to better understand the formation and prevention of the stones, focus should shift away from the long-held focus on specific gut bacterium, such as Oxalobacter formigenesm,to apparent systems-level microbial imbalances.

METHODOLOGY:

• The authors evaluated the gut, urinary, and oral microbiota of 83 patients having kidney stones surgically removed at St. Joseph’s Hospital in London, Ontario, and compared them to 30 healthy controls recruited between August 2015 and January 2019.
• Analysis using measures including shotgun metagenomic sequencing were used to identify specific gut bacteria and the genetic capabilities of the bacteria, and simpler sequencing was conducted using oral and urinary microbiota samples.
• Patients had no antibiotic exposure within the previous 90 days.

TAKEAWAY:

• Significant differences were observed in disturbances in microbiota in all three microbiomes among those who did and did not form kidney stones.
• Patients who formed kidney stones also showed more antibiotic-resistant genes, suggesting greater exposure to antimicrobials.
• Those who had formed kidney stones had reduced taxonomic and functional diversity compared with healthy controls.
• Core functional bioenergetic pathways had been replaced with virulence-associated gene markers in gut and urinary microbiota in those with kidney stones.
• And community network microbiota had collapsed among those with kidney stones.
• “These multisite microbial community shifts may be the result of deleterious environmental factors including antibiotic exposure,” the authors speculated.
• However, no differences were observed between the cohorts in terms of oxalate metabolism — commonly considered a culprit in kidney stone formation.

IN PRACTICE:

• “We found not only that those who got kidney stones had an unhealthy microbiome, including a gut microbiome that was more likely to excrete toxins to the kidneys, but also that they were antibiotic resistant,” explains senior author Jeremy Burton, PhD, the Lawson Scientist and Research Chair of Human Microbiome and Probiotics at St. Joseph’s Health Care London, in a press statement.
• “We conclude that multisite microbiota alteration is a hallmark of stone formation, and kidney stone disease treatment should consider microbial functional restoration and the avoidance of aberrant modulators such as poor diet and antibiotics, where applicable, to prevent stone recurrence,” the authors further wrote in the study.
• “Based on these findings, we suggest that the historic emphasis put on O formigenes and other direct oxalate-handling taxa should be discontinued in favor of mechanistic study into the apparent systems-level microbial imbalances in kidney stone formers,” they said.

SOURCE:

The study was published in Microbiome.

It was conducted by the first author Kait F. Al, PhD, of the department of microbiology and immunology, The University of Western Ontario, London, and colleagues. 

LIMITATIONS:

The sampling techniques used in the study provide relative compositional but not absolute abundance information, and the sequencing methods do not provide taxonomic annotation to the species level in all cases.

“For this reason, as well as the problematic nature of comparison across sequencing methodologies, caution should be taken when comparing these data and taxonomic annotations in future studies,” the authors noted.

Furthermore, as the study was observational, causality of stone disease cannot be established to the differences detected between the microbiota of healthy control individuals and those with kidney stones. 

DISCLOSURES:

The authors had no disclosures to report.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Gut and urinary microbiota alterations appear to play key roles in the development of kidney stones, suggesting that avoidance of modulators such as a poor diet and antibiotic use could help prevent kidney stone recurrence. 

Kidney stones are commonly formed by calcium oxalate produced by the body, but the findings suggest that in efforts to better understand the formation and prevention of the stones, focus should shift away from the long-held focus on specific gut bacterium, such as Oxalobacter formigenesm,to apparent systems-level microbial imbalances.

METHODOLOGY:

• The authors evaluated the gut, urinary, and oral microbiota of 83 patients having kidney stones surgically removed at St. Joseph’s Hospital in London, Ontario, and compared them to 30 healthy controls recruited between August 2015 and January 2019.
• Analysis using measures including shotgun metagenomic sequencing were used to identify specific gut bacteria and the genetic capabilities of the bacteria, and simpler sequencing was conducted using oral and urinary microbiota samples.
• Patients had no antibiotic exposure within the previous 90 days.

TAKEAWAY:

• Significant differences were observed in disturbances in microbiota in all three microbiomes among those who did and did not form kidney stones.
• Patients who formed kidney stones also showed more antibiotic-resistant genes, suggesting greater exposure to antimicrobials.
• Those who had formed kidney stones had reduced taxonomic and functional diversity compared with healthy controls.
• Core functional bioenergetic pathways had been replaced with virulence-associated gene markers in gut and urinary microbiota in those with kidney stones.
• And community network microbiota had collapsed among those with kidney stones.
• “These multisite microbial community shifts may be the result of deleterious environmental factors including antibiotic exposure,” the authors speculated.
• However, no differences were observed between the cohorts in terms of oxalate metabolism — commonly considered a culprit in kidney stone formation.

IN PRACTICE:

• “We found not only that those who got kidney stones had an unhealthy microbiome, including a gut microbiome that was more likely to excrete toxins to the kidneys, but also that they were antibiotic resistant,” explains senior author Jeremy Burton, PhD, the Lawson Scientist and Research Chair of Human Microbiome and Probiotics at St. Joseph’s Health Care London, in a press statement.
• “We conclude that multisite microbiota alteration is a hallmark of stone formation, and kidney stone disease treatment should consider microbial functional restoration and the avoidance of aberrant modulators such as poor diet and antibiotics, where applicable, to prevent stone recurrence,” the authors further wrote in the study.
• “Based on these findings, we suggest that the historic emphasis put on O formigenes and other direct oxalate-handling taxa should be discontinued in favor of mechanistic study into the apparent systems-level microbial imbalances in kidney stone formers,” they said.

SOURCE:

The study was published in Microbiome.

It was conducted by the first author Kait F. Al, PhD, of the department of microbiology and immunology, The University of Western Ontario, London, and colleagues. 

LIMITATIONS:

The sampling techniques used in the study provide relative compositional but not absolute abundance information, and the sequencing methods do not provide taxonomic annotation to the species level in all cases.

“For this reason, as well as the problematic nature of comparison across sequencing methodologies, caution should be taken when comparing these data and taxonomic annotations in future studies,” the authors noted.

Furthermore, as the study was observational, causality of stone disease cannot be established to the differences detected between the microbiota of healthy control individuals and those with kidney stones. 

DISCLOSURES:

The authors had no disclosures to report.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Gut and urinary microbiota alterations appear to play key roles in the development of kidney stones, suggesting that avoidance of modulators such as a poor diet and antibiotic use could help prevent kidney stone recurrence. 

Kidney stones are commonly formed by calcium oxalate produced by the body, but the findings suggest that in efforts to better understand the formation and prevention of the stones, focus should shift away from the long-held focus on specific gut bacterium, such as Oxalobacter formigenesm,to apparent systems-level microbial imbalances.

METHODOLOGY:

• The authors evaluated the gut, urinary, and oral microbiota of 83 patients having kidney stones surgically removed at St. Joseph’s Hospital in London, Ontario, and compared them to 30 healthy controls recruited between August 2015 and January 2019.
• Analysis using measures including shotgun metagenomic sequencing were used to identify specific gut bacteria and the genetic capabilities of the bacteria, and simpler sequencing was conducted using oral and urinary microbiota samples.
• Patients had no antibiotic exposure within the previous 90 days.

TAKEAWAY:

• Significant differences were observed in disturbances in microbiota in all three microbiomes among those who did and did not form kidney stones.
• Patients who formed kidney stones also showed more antibiotic-resistant genes, suggesting greater exposure to antimicrobials.
• Those who had formed kidney stones had reduced taxonomic and functional diversity compared with healthy controls.
• Core functional bioenergetic pathways had been replaced with virulence-associated gene markers in gut and urinary microbiota in those with kidney stones.
• And community network microbiota had collapsed among those with kidney stones.
• “These multisite microbial community shifts may be the result of deleterious environmental factors including antibiotic exposure,” the authors speculated.
• However, no differences were observed between the cohorts in terms of oxalate metabolism — commonly considered a culprit in kidney stone formation.

IN PRACTICE:

• “We found not only that those who got kidney stones had an unhealthy microbiome, including a gut microbiome that was more likely to excrete toxins to the kidneys, but also that they were antibiotic resistant,” explains senior author Jeremy Burton, PhD, the Lawson Scientist and Research Chair of Human Microbiome and Probiotics at St. Joseph’s Health Care London, in a press statement.
• “We conclude that multisite microbiota alteration is a hallmark of stone formation, and kidney stone disease treatment should consider microbial functional restoration and the avoidance of aberrant modulators such as poor diet and antibiotics, where applicable, to prevent stone recurrence,” the authors further wrote in the study.
• “Based on these findings, we suggest that the historic emphasis put on O formigenes and other direct oxalate-handling taxa should be discontinued in favor of mechanistic study into the apparent systems-level microbial imbalances in kidney stone formers,” they said.

SOURCE:

The study was published in Microbiome.

It was conducted by the first author Kait F. Al, PhD, of the department of microbiology and immunology, The University of Western Ontario, London, and colleagues. 

LIMITATIONS:

The sampling techniques used in the study provide relative compositional but not absolute abundance information, and the sequencing methods do not provide taxonomic annotation to the species level in all cases.

“For this reason, as well as the problematic nature of comparison across sequencing methodologies, caution should be taken when comparing these data and taxonomic annotations in future studies,” the authors noted.

Furthermore, as the study was observational, causality of stone disease cannot be established to the differences detected between the microbiota of healthy control individuals and those with kidney stones. 

DISCLOSURES:

The authors had no disclosures to report.
 

A version of this article appeared on Medscape.com.