ASN Kidney Week 2019

WASHINGTON – A novel antibody, obinutuzumab, enhances renal responses in patients with lupus nephritis, through more complete B-cell depletion, compared with standard immunotherapy, and is well tolerated, according to results from the phase 2 NOBILITY trial.

“We know from our previous trials with anti–B-cell antibodies that results were mixed and we felt that these variable results were possibly due to variability in B-cell depletion with a type 1 anti-CD20 antibody such as rituximab,” Brad Rovin, MD, director, division of nephrology, Ohio State University in Columbus, told a press briefing here at Kidney Week 2019: American Society of Nephrology annual meeting.

“So we hypothesized that if we could deplete B cells more efficiently and completely, we would achieve better results. At week 52, 35% of patients in the obinutuzumab-treated group achieved a complete renal response, compared to 23% in the standard-of-care arm.”

And by week 76, the difference between obinutuzumab and the standard of care was actually larger at 40% vs. 18%, respectively, “and this was statistically significant at a P value of .01,” added Dr. Rovin, who presented the full findings of the study at the conference.

Obinutuzumab, a highly engineered anti-CD20 antibody, is already approved under the brand name Gazyva for use in certain leukemias and lymphomas. The NOBILITY study was funded by Genentech-Roche, and Dr. Rovin reported being a consultant for the company.

Asked by Medscape Medical News to comment on the study, Duvuru Geetha, MBBS, noted that with standard-of-care mycophenolate mofetil (MMF) plus corticosteroids, “the remissions rates we achieve [for lupus nephritis] are still not great,” ranging from 30% to 50%, depending on the patient population.

“This is why there is a need for alternative agents,” added Dr. Geetha, who is an associate professor of medicine, Johns Hopkins University, Baltimore.

With obinutuzumab, “the data look very promising because there is a much more profound and sustained effect on B-cell depletion and the renal response rate is much higher [than with MMF and corticosteroids],” she noted.

Dr. Geetha added, however, that she presumes patients were all premedicated with prophylactic agents to prevent infectious events, as they are when treated with rituximab.

“I think what is definitely different about this drug is that it induces direct cell death more efficiently than rituximab and that is probably what’s accounting for the higher efficacy seen with it,” said Dr. Geetha, who disclosed having received honoraria from Genentech a number of years ago.

“So yes, I believe the results are clinically meaningful,” she concluded.

NOBILITY study design

The NOBILITY trial randomized 125 patients with Class III or IV lupus nephritis to either obinutuzumab plus MMF and corticosteroids, or to MMF plus corticosteroids alone, for a treatment interval of 104 weeks.

Patients in the obinutuzumab group received two infusions of the highly engineered anti-CD20 antibody at week 0 and week 2 and another two infusions at 6 months.

“The primary endpoint was complete renal response at week 52,” the authors wrote, “while key secondary endpoints included overall renal response and modified complete renal response.”

Both at week 52 and week 76, more patients in the obinutuzumab group achieved an overall renal response as well as a modified complete renal response, compared with those treated with immunosuppression alone.

“If you look at the complete renal response over time, you can see that the curves separate after about 6 months but the placebo group starts to decline as you go further out, whereas the obinutuzumab group continues to separate, so my prediction is that we are going to see this trend continue because of the mechanism of action of obinutuzumab,” Dr. Rovin explained.

Phase 3 trials to start early 2020

All of the serologies relevant to lupus and lupus nephritis “including C3 and C4 improved while antidoubled stranded DNA levels declined, as did the urine protein-to-creatinine ratio, although the decline was more rapid and more profound in the obinutuzumab-treated patients,” Dr. Rovin said.

Importantly as well, despite the profound B-cell depletion produced by obinutuzumab, “the adverse event profile of this drug was very similar to the placebo group,” he stressed.

As expected, rates of infusion reactions were slightly higher in the experimental group than the immunosuppression alone group, but rates of serious adverse events were the same between groups, as were adverse infectious events, he noted.

Investigators have now initiated a global phase 3 trial, scheduled to start in early 2020, to evaluate the same treatment protocol in a larger group of patients.


Kidney Week 2019. Abstract #FR-OR136. Presented Nov. 8, 2019.
 

This story first appeared on Medscape.com.

WASHINGTON – A novel antibody, obinutuzumab, enhances renal responses in patients with lupus nephritis, through more complete B-cell depletion, compared with standard immunotherapy, and is well tolerated, according to results from the phase 2 NOBILITY trial.

“We know from our previous trials with anti–B-cell antibodies that results were mixed and we felt that these variable results were possibly due to variability in B-cell depletion with a type 1 anti-CD20 antibody such as rituximab,” Brad Rovin, MD, director, division of nephrology, Ohio State University in Columbus, told a press briefing here at Kidney Week 2019: American Society of Nephrology annual meeting.

“So we hypothesized that if we could deplete B cells more efficiently and completely, we would achieve better results. At week 52, 35% of patients in the obinutuzumab-treated group achieved a complete renal response, compared to 23% in the standard-of-care arm.”

And by week 76, the difference between obinutuzumab and the standard of care was actually larger at 40% vs. 18%, respectively, “and this was statistically significant at a P value of .01,” added Dr. Rovin, who presented the full findings of the study at the conference.

Obinutuzumab, a highly engineered anti-CD20 antibody, is already approved under the brand name Gazyva for use in certain leukemias and lymphomas. The NOBILITY study was funded by Genentech-Roche, and Dr. Rovin reported being a consultant for the company.

Asked by Medscape Medical News to comment on the study, Duvuru Geetha, MBBS, noted that with standard-of-care mycophenolate mofetil (MMF) plus corticosteroids, “the remissions rates we achieve [for lupus nephritis] are still not great,” ranging from 30% to 50%, depending on the patient population.

“This is why there is a need for alternative agents,” added Dr. Geetha, who is an associate professor of medicine, Johns Hopkins University, Baltimore.

With obinutuzumab, “the data look very promising because there is a much more profound and sustained effect on B-cell depletion and the renal response rate is much higher [than with MMF and corticosteroids],” she noted.

Dr. Geetha added, however, that she presumes patients were all premedicated with prophylactic agents to prevent infectious events, as they are when treated with rituximab.

“I think what is definitely different about this drug is that it induces direct cell death more efficiently than rituximab and that is probably what’s accounting for the higher efficacy seen with it,” said Dr. Geetha, who disclosed having received honoraria from Genentech a number of years ago.

“So yes, I believe the results are clinically meaningful,” she concluded.

NOBILITY study design

The NOBILITY trial randomized 125 patients with Class III or IV lupus nephritis to either obinutuzumab plus MMF and corticosteroids, or to MMF plus corticosteroids alone, for a treatment interval of 104 weeks.

Patients in the obinutuzumab group received two infusions of the highly engineered anti-CD20 antibody at week 0 and week 2 and another two infusions at 6 months.

“The primary endpoint was complete renal response at week 52,” the authors wrote, “while key secondary endpoints included overall renal response and modified complete renal response.”

Both at week 52 and week 76, more patients in the obinutuzumab group achieved an overall renal response as well as a modified complete renal response, compared with those treated with immunosuppression alone.

“If you look at the complete renal response over time, you can see that the curves separate after about 6 months but the placebo group starts to decline as you go further out, whereas the obinutuzumab group continues to separate, so my prediction is that we are going to see this trend continue because of the mechanism of action of obinutuzumab,” Dr. Rovin explained.

Phase 3 trials to start early 2020

All of the serologies relevant to lupus and lupus nephritis “including C3 and C4 improved while antidoubled stranded DNA levels declined, as did the urine protein-to-creatinine ratio, although the decline was more rapid and more profound in the obinutuzumab-treated patients,” Dr. Rovin said.

Importantly as well, despite the profound B-cell depletion produced by obinutuzumab, “the adverse event profile of this drug was very similar to the placebo group,” he stressed.

As expected, rates of infusion reactions were slightly higher in the experimental group than the immunosuppression alone group, but rates of serious adverse events were the same between groups, as were adverse infectious events, he noted.

Investigators have now initiated a global phase 3 trial, scheduled to start in early 2020, to evaluate the same treatment protocol in a larger group of patients.


Kidney Week 2019. Abstract #FR-OR136. Presented Nov. 8, 2019.
 

This story first appeared on Medscape.com.

WASHINGTON – A novel antibody, obinutuzumab, enhances renal responses in patients with lupus nephritis, through more complete B-cell depletion, compared with standard immunotherapy, and is well tolerated, according to results from the phase 2 NOBILITY trial.

“We know from our previous trials with anti–B-cell antibodies that results were mixed and we felt that these variable results were possibly due to variability in B-cell depletion with a type 1 anti-CD20 antibody such as rituximab,” Brad Rovin, MD, director, division of nephrology, Ohio State University in Columbus, told a press briefing here at Kidney Week 2019: American Society of Nephrology annual meeting.

“So we hypothesized that if we could deplete B cells more efficiently and completely, we would achieve better results. At week 52, 35% of patients in the obinutuzumab-treated group achieved a complete renal response, compared to 23% in the standard-of-care arm.”

And by week 76, the difference between obinutuzumab and the standard of care was actually larger at 40% vs. 18%, respectively, “and this was statistically significant at a P value of .01,” added Dr. Rovin, who presented the full findings of the study at the conference.

Obinutuzumab, a highly engineered anti-CD20 antibody, is already approved under the brand name Gazyva for use in certain leukemias and lymphomas. The NOBILITY study was funded by Genentech-Roche, and Dr. Rovin reported being a consultant for the company.

Asked by Medscape Medical News to comment on the study, Duvuru Geetha, MBBS, noted that with standard-of-care mycophenolate mofetil (MMF) plus corticosteroids, “the remissions rates we achieve [for lupus nephritis] are still not great,” ranging from 30% to 50%, depending on the patient population.

“This is why there is a need for alternative agents,” added Dr. Geetha, who is an associate professor of medicine, Johns Hopkins University, Baltimore.

With obinutuzumab, “the data look very promising because there is a much more profound and sustained effect on B-cell depletion and the renal response rate is much higher [than with MMF and corticosteroids],” she noted.

Dr. Geetha added, however, that she presumes patients were all premedicated with prophylactic agents to prevent infectious events, as they are when treated with rituximab.

“I think what is definitely different about this drug is that it induces direct cell death more efficiently than rituximab and that is probably what’s accounting for the higher efficacy seen with it,” said Dr. Geetha, who disclosed having received honoraria from Genentech a number of years ago.

“So yes, I believe the results are clinically meaningful,” she concluded.

NOBILITY study design

The NOBILITY trial randomized 125 patients with Class III or IV lupus nephritis to either obinutuzumab plus MMF and corticosteroids, or to MMF plus corticosteroids alone, for a treatment interval of 104 weeks.

Patients in the obinutuzumab group received two infusions of the highly engineered anti-CD20 antibody at week 0 and week 2 and another two infusions at 6 months.

“The primary endpoint was complete renal response at week 52,” the authors wrote, “while key secondary endpoints included overall renal response and modified complete renal response.”

Both at week 52 and week 76, more patients in the obinutuzumab group achieved an overall renal response as well as a modified complete renal response, compared with those treated with immunosuppression alone.

“If you look at the complete renal response over time, you can see that the curves separate after about 6 months but the placebo group starts to decline as you go further out, whereas the obinutuzumab group continues to separate, so my prediction is that we are going to see this trend continue because of the mechanism of action of obinutuzumab,” Dr. Rovin explained.

Phase 3 trials to start early 2020

All of the serologies relevant to lupus and lupus nephritis “including C3 and C4 improved while antidoubled stranded DNA levels declined, as did the urine protein-to-creatinine ratio, although the decline was more rapid and more profound in the obinutuzumab-treated patients,” Dr. Rovin said.

Importantly as well, despite the profound B-cell depletion produced by obinutuzumab, “the adverse event profile of this drug was very similar to the placebo group,” he stressed.

As expected, rates of infusion reactions were slightly higher in the experimental group than the immunosuppression alone group, but rates of serious adverse events were the same between groups, as were adverse infectious events, he noted.

Investigators have now initiated a global phase 3 trial, scheduled to start in early 2020, to evaluate the same treatment protocol in a larger group of patients.


Kidney Week 2019. Abstract #FR-OR136. Presented Nov. 8, 2019.
 

This story first appeared on Medscape.com.

Data from more than 5 million individuals has been used to develop an equation for predicting the risk of incident chronic kidney disease (CKD) in people with or without diabetes, according to a presentation at Kidney Week 2019, sponsored by the American Society of Nephrology.

In a paper published simultaneously online in JAMA, researchers reported the outcome of an individual-level data analysis of 34 multinational cohorts involving 5,222,711 individuals – including 781,627 with diabetes – from 28 countries as part of the Chronic Kidney Disease Prognosis Consortium.

“An equation for kidney failure risk may help improve care for patients with established CKD, but relatively little work has been performed to develop predictive tools to identify those at increased risk of developing CKD – defined by reduced eGFR [estimated glomerular filtration rate], despite the high lifetime risk of CKD – which is estimated to be 59.1% in the United States,” wrote Robert G. Nelson, MD, PhD, from the National Institute of Diabetes and Digestive and Kidney Diseases in Phoenix and colleagues.

Over a mean follow-up of 4 years, 15% of individuals without diabetes and 40% of individuals with diabetes developed incident chronic kidney disease, defined as an eGFR below 60 mL/min per 1.73m².

The key risk factors were older age, female sex, black race, hypertension, history of cardiovascular disease, lower eGFR values, and higher urine albumin to creatinine ratio. Smoking was also significantly associated with reduced eGFR but only in cohorts without diabetes. In cohorts with diabetes, elevated hemoglobin A_1c and the presence and type of diabetes medication were also significantly associated with reduced eGFR.

Using this information, the researchers developed a prediction model built from weighted-average hazard ratios and validated it in nine external validation cohorts of 18 study populations involving a total of 2,253,540 individuals. They found that in 16 of the 18 study populations, the slope of observed to predicted risk ranged from 0.80 to 1.25.

Moreover, in the cohorts without diabetes, the risk equations had a median C-statistic for the 5-year predicted probability of 0.845 (interquartile range, 0.789-0.890) and of 0.801 (IQR, 0.750-0.819) in the cohorts with diabetes, the investigators reported.

“Several models have been developed for estimating the risk of prevalent and incident CKD and end-stage kidney disease, but even those with good discriminative performance have not always performed well for cohorts of people outside the original derivation cohort,” the authors wrote. They argued that their model “demonstrated high discrimination and variable calibration in diverse populations.”

However, they stressed that further study was needed to determine if use of the equations would actually lead to improvements in clinical care and patient outcomes. In an accompanying editorial, Sri Lekha Tummalapalli, MD, and Michelle M. Estrella, MD, of the Kidney Health Research Collaborative at the University of California, San Francisco, said the study and its focus on primary, rather than secondary, prevention of kidney disease is a critical step toward reducing the burden of that disease, especially given that an estimated 37 million people in the United States have chronic kidney disease.

It is also important, they added, that primary prevention of kidney disease is tailored to the individual patient’s risk because risk prediction and screening strategies are unlikely to improve outcomes if they are not paired with effective individualized interventions, such as lifestyle modification or management of blood pressure.

These risk equations could be more holistic by integrating the prediction of both elevated albuminuria and reduced eGFR because more than 40% of individuals with chronic kidney disease have increased albuminuria without reduced eGFR, they noted (JAMA. 2019 Nov 8. doi: 10.1001/jama.2019.17378).

The study and CKD Prognosis Consortium were supported by the U.S. National Kidney Foundation and the National Institute of Diabetes and Digestive and Kidney Diseases. One author was supported by a grant from the German Research Foundation. Nine authors declared grants, consultancies, and other support from the private sector and research organizations. No other conflicts of interest were declared. Dr. Tummalapalli and Dr. Estrella reported no conflicts of interest.

SOURCE: Nelson R et al. JAMA. 2019 Nov 8. doi: 10.1001/jama.2019.17379.

Data from more than 5 million individuals has been used to develop an equation for predicting the risk of incident chronic kidney disease (CKD) in people with or without diabetes, according to a presentation at Kidney Week 2019, sponsored by the American Society of Nephrology.

In a paper published simultaneously online in JAMA, researchers reported the outcome of an individual-level data analysis of 34 multinational cohorts involving 5,222,711 individuals – including 781,627 with diabetes – from 28 countries as part of the Chronic Kidney Disease Prognosis Consortium.

“An equation for kidney failure risk may help improve care for patients with established CKD, but relatively little work has been performed to develop predictive tools to identify those at increased risk of developing CKD – defined by reduced eGFR [estimated glomerular filtration rate], despite the high lifetime risk of CKD – which is estimated to be 59.1% in the United States,” wrote Robert G. Nelson, MD, PhD, from the National Institute of Diabetes and Digestive and Kidney Diseases in Phoenix and colleagues.

Over a mean follow-up of 4 years, 15% of individuals without diabetes and 40% of individuals with diabetes developed incident chronic kidney disease, defined as an eGFR below 60 mL/min per 1.73m².

The key risk factors were older age, female sex, black race, hypertension, history of cardiovascular disease, lower eGFR values, and higher urine albumin to creatinine ratio. Smoking was also significantly associated with reduced eGFR but only in cohorts without diabetes. In cohorts with diabetes, elevated hemoglobin A_1c and the presence and type of diabetes medication were also significantly associated with reduced eGFR.

Using this information, the researchers developed a prediction model built from weighted-average hazard ratios and validated it in nine external validation cohorts of 18 study populations involving a total of 2,253,540 individuals. They found that in 16 of the 18 study populations, the slope of observed to predicted risk ranged from 0.80 to 1.25.

Moreover, in the cohorts without diabetes, the risk equations had a median C-statistic for the 5-year predicted probability of 0.845 (interquartile range, 0.789-0.890) and of 0.801 (IQR, 0.750-0.819) in the cohorts with diabetes, the investigators reported.

“Several models have been developed for estimating the risk of prevalent and incident CKD and end-stage kidney disease, but even those with good discriminative performance have not always performed well for cohorts of people outside the original derivation cohort,” the authors wrote. They argued that their model “demonstrated high discrimination and variable calibration in diverse populations.”

However, they stressed that further study was needed to determine if use of the equations would actually lead to improvements in clinical care and patient outcomes. In an accompanying editorial, Sri Lekha Tummalapalli, MD, and Michelle M. Estrella, MD, of the Kidney Health Research Collaborative at the University of California, San Francisco, said the study and its focus on primary, rather than secondary, prevention of kidney disease is a critical step toward reducing the burden of that disease, especially given that an estimated 37 million people in the United States have chronic kidney disease.

It is also important, they added, that primary prevention of kidney disease is tailored to the individual patient’s risk because risk prediction and screening strategies are unlikely to improve outcomes if they are not paired with effective individualized interventions, such as lifestyle modification or management of blood pressure.

These risk equations could be more holistic by integrating the prediction of both elevated albuminuria and reduced eGFR because more than 40% of individuals with chronic kidney disease have increased albuminuria without reduced eGFR, they noted (JAMA. 2019 Nov 8. doi: 10.1001/jama.2019.17378).

The study and CKD Prognosis Consortium were supported by the U.S. National Kidney Foundation and the National Institute of Diabetes and Digestive and Kidney Diseases. One author was supported by a grant from the German Research Foundation. Nine authors declared grants, consultancies, and other support from the private sector and research organizations. No other conflicts of interest were declared. Dr. Tummalapalli and Dr. Estrella reported no conflicts of interest.

SOURCE: Nelson R et al. JAMA. 2019 Nov 8. doi: 10.1001/jama.2019.17379.

Data from more than 5 million individuals has been used to develop an equation for predicting the risk of incident chronic kidney disease (CKD) in people with or without diabetes, according to a presentation at Kidney Week 2019, sponsored by the American Society of Nephrology.

In a paper published simultaneously online in JAMA, researchers reported the outcome of an individual-level data analysis of 34 multinational cohorts involving 5,222,711 individuals – including 781,627 with diabetes – from 28 countries as part of the Chronic Kidney Disease Prognosis Consortium.

“An equation for kidney failure risk may help improve care for patients with established CKD, but relatively little work has been performed to develop predictive tools to identify those at increased risk of developing CKD – defined by reduced eGFR [estimated glomerular filtration rate], despite the high lifetime risk of CKD – which is estimated to be 59.1% in the United States,” wrote Robert G. Nelson, MD, PhD, from the National Institute of Diabetes and Digestive and Kidney Diseases in Phoenix and colleagues.

Over a mean follow-up of 4 years, 15% of individuals without diabetes and 40% of individuals with diabetes developed incident chronic kidney disease, defined as an eGFR below 60 mL/min per 1.73m².

The key risk factors were older age, female sex, black race, hypertension, history of cardiovascular disease, lower eGFR values, and higher urine albumin to creatinine ratio. Smoking was also significantly associated with reduced eGFR but only in cohorts without diabetes. In cohorts with diabetes, elevated hemoglobin A_1c and the presence and type of diabetes medication were also significantly associated with reduced eGFR.

Using this information, the researchers developed a prediction model built from weighted-average hazard ratios and validated it in nine external validation cohorts of 18 study populations involving a total of 2,253,540 individuals. They found that in 16 of the 18 study populations, the slope of observed to predicted risk ranged from 0.80 to 1.25.

Moreover, in the cohorts without diabetes, the risk equations had a median C-statistic for the 5-year predicted probability of 0.845 (interquartile range, 0.789-0.890) and of 0.801 (IQR, 0.750-0.819) in the cohorts with diabetes, the investigators reported.

“Several models have been developed for estimating the risk of prevalent and incident CKD and end-stage kidney disease, but even those with good discriminative performance have not always performed well for cohorts of people outside the original derivation cohort,” the authors wrote. They argued that their model “demonstrated high discrimination and variable calibration in diverse populations.”

However, they stressed that further study was needed to determine if use of the equations would actually lead to improvements in clinical care and patient outcomes. In an accompanying editorial, Sri Lekha Tummalapalli, MD, and Michelle M. Estrella, MD, of the Kidney Health Research Collaborative at the University of California, San Francisco, said the study and its focus on primary, rather than secondary, prevention of kidney disease is a critical step toward reducing the burden of that disease, especially given that an estimated 37 million people in the United States have chronic kidney disease.

It is also important, they added, that primary prevention of kidney disease is tailored to the individual patient’s risk because risk prediction and screening strategies are unlikely to improve outcomes if they are not paired with effective individualized interventions, such as lifestyle modification or management of blood pressure.

These risk equations could be more holistic by integrating the prediction of both elevated albuminuria and reduced eGFR because more than 40% of individuals with chronic kidney disease have increased albuminuria without reduced eGFR, they noted (JAMA. 2019 Nov 8. doi: 10.1001/jama.2019.17378).

The study and CKD Prognosis Consortium were supported by the U.S. National Kidney Foundation and the National Institute of Diabetes and Digestive and Kidney Diseases. One author was supported by a grant from the German Research Foundation. Nine authors declared grants, consultancies, and other support from the private sector and research organizations. No other conflicts of interest were declared. Dr. Tummalapalli and Dr. Estrella reported no conflicts of interest.

SOURCE: Nelson R et al. JAMA. 2019 Nov 8. doi: 10.1001/jama.2019.17379.

A new study has found that neither vitamin D nor omega-3 fatty acids are significantly more beneficial than placebo for prevention and treatment of chronic kidney disease in patients with type 2 diabetes, according to Ian H. de Boer, MD, of the University of Washington, Seattle, and coauthors.

Findings of the study were presented at Kidney Week 2019, sponsored the American Society of Nephrology, and published simultaneously in JAMA.

To determine the benefits of either vitamin D or omega-3 fatty acids in regard to kidney function, the researchers conducted a randomized clinical trial of 1,312 patients with type 2 diabetes. The trial was designed to accompany the Vitamin D and Omega-3 Trial (VITAL), which enrolled 25,871 patients to test the two supplements in the prevention of cardiovascular disease and cancer.

Participants in this study – known as VITAL–Diabetic Kidney Disease, designed as an ancillary to VITAL – were assigned to one of four groups: vitamin D plus omega-3 fatty acids (n = 370), vitamin D plus placebo (n = 333), omega-3 fatty acids plus placebo (n = 289), or both placebos (n = 320). The goal was to assess changes in in glomerular filtration rate estimated from serum creatinine and cystatin C (eGFR) after 5 years.

Of the initial 1,312 participants, 934 (71%) finished the study. At 5-year follow-up, patients taking vitamin D had a mean change in eGFR of −12.3 mL/min per 1.73 m² (95% confidence interval, −13.4 to −11.2), compared with −13.1 mL/min per 1.73 m² (95% CI, −14.2 to −11.9) with placebo. Patients taking omega-3 fatty acids had a mean eGFR change of −12.2 mL/min per 1.73 m² (95% CI, −13.3 to −11.1), compared with −13.1 mL/min per 1.73 m² (95% CI, −14.2 to −12.0) with placebo.

The authors noted that the modest number of measurements collected per participant limited the evaluation and analyses. In addition, the study focused broadly on the type 2 diabetes population and not on subgroups, “who may derive more benefit from the study interventions.”

In an accompanying editorial, authors Anika Lucas, MD and Myles Wolf, MD, of Duke University in Durham, N.C., said multiple clinical trials, including this latest study from de Boer and colleagues on kidney function, have failed to reinforce the previously reported benefits of vitamin D.

“The VITAL-DKD study population had nearly normal mean 25-hydroxyvitamin D levels at baseline, leaving open the question of whether the results would have differed had recruitment been restricted to patients with moderate or severe vitamin D deficiency,” they wrote (JAMA. 2019 Nov 8. doi: 10.1001/jama.2019.17302).

Nevertheless, it seems safe to conclude that the previous associations between vitamin D deficiency and adverse health were “driven by unmeasured residual confounding or reverse causality.

“Without certainty about the ideal approach to vitamin D treatment in advanced CKD, a randomized trial that compared cholecalciferol, exogenous 25-hydroxyvitamin D, and an activated vitamin D analogue vs. placebo could definitively lay to rest multiple remaining questions in the area,” they suggested.

The National Institute of Diabetes and Digestive and Kidney Diseases funded the study. The authors reported numerous potential conflicts of interest, including receiving grants, consulting fees, and equipment and supplies from various pharmaceutical companies and the National Institutes of Health. Dr. Wolf reported having served as a consultant for Akebia, AMAG, Amgen, Ardelyx, Diasorin, and Pharmacosmos. No other disclosures were reported.

SOURCE: de Boer IH et al. JAMA. 2019 Nov 8. doi: 10.1001/jama.2019.17380.

A new study has found that neither vitamin D nor omega-3 fatty acids are significantly more beneficial than placebo for prevention and treatment of chronic kidney disease in patients with type 2 diabetes, according to Ian H. de Boer, MD, of the University of Washington, Seattle, and coauthors.

Findings of the study were presented at Kidney Week 2019, sponsored the American Society of Nephrology, and published simultaneously in JAMA.

To determine the benefits of either vitamin D or omega-3 fatty acids in regard to kidney function, the researchers conducted a randomized clinical trial of 1,312 patients with type 2 diabetes. The trial was designed to accompany the Vitamin D and Omega-3 Trial (VITAL), which enrolled 25,871 patients to test the two supplements in the prevention of cardiovascular disease and cancer.

Participants in this study – known as VITAL–Diabetic Kidney Disease, designed as an ancillary to VITAL – were assigned to one of four groups: vitamin D plus omega-3 fatty acids (n = 370), vitamin D plus placebo (n = 333), omega-3 fatty acids plus placebo (n = 289), or both placebos (n = 320). The goal was to assess changes in in glomerular filtration rate estimated from serum creatinine and cystatin C (eGFR) after 5 years.

Of the initial 1,312 participants, 934 (71%) finished the study. At 5-year follow-up, patients taking vitamin D had a mean change in eGFR of −12.3 mL/min per 1.73 m² (95% confidence interval, −13.4 to −11.2), compared with −13.1 mL/min per 1.73 m² (95% CI, −14.2 to −11.9) with placebo. Patients taking omega-3 fatty acids had a mean eGFR change of −12.2 mL/min per 1.73 m² (95% CI, −13.3 to −11.1), compared with −13.1 mL/min per 1.73 m² (95% CI, −14.2 to −12.0) with placebo.

The authors noted that the modest number of measurements collected per participant limited the evaluation and analyses. In addition, the study focused broadly on the type 2 diabetes population and not on subgroups, “who may derive more benefit from the study interventions.”

In an accompanying editorial, authors Anika Lucas, MD and Myles Wolf, MD, of Duke University in Durham, N.C., said multiple clinical trials, including this latest study from de Boer and colleagues on kidney function, have failed to reinforce the previously reported benefits of vitamin D.

“The VITAL-DKD study population had nearly normal mean 25-hydroxyvitamin D levels at baseline, leaving open the question of whether the results would have differed had recruitment been restricted to patients with moderate or severe vitamin D deficiency,” they wrote (JAMA. 2019 Nov 8. doi: 10.1001/jama.2019.17302).

Nevertheless, it seems safe to conclude that the previous associations between vitamin D deficiency and adverse health were “driven by unmeasured residual confounding or reverse causality.

“Without certainty about the ideal approach to vitamin D treatment in advanced CKD, a randomized trial that compared cholecalciferol, exogenous 25-hydroxyvitamin D, and an activated vitamin D analogue vs. placebo could definitively lay to rest multiple remaining questions in the area,” they suggested.

The National Institute of Diabetes and Digestive and Kidney Diseases funded the study. The authors reported numerous potential conflicts of interest, including receiving grants, consulting fees, and equipment and supplies from various pharmaceutical companies and the National Institutes of Health. Dr. Wolf reported having served as a consultant for Akebia, AMAG, Amgen, Ardelyx, Diasorin, and Pharmacosmos. No other disclosures were reported.

SOURCE: de Boer IH et al. JAMA. 2019 Nov 8. doi: 10.1001/jama.2019.17380.

A new study has found that neither vitamin D nor omega-3 fatty acids are significantly more beneficial than placebo for prevention and treatment of chronic kidney disease in patients with type 2 diabetes, according to Ian H. de Boer, MD, of the University of Washington, Seattle, and coauthors.

Findings of the study were presented at Kidney Week 2019, sponsored the American Society of Nephrology, and published simultaneously in JAMA.

To determine the benefits of either vitamin D or omega-3 fatty acids in regard to kidney function, the researchers conducted a randomized clinical trial of 1,312 patients with type 2 diabetes. The trial was designed to accompany the Vitamin D and Omega-3 Trial (VITAL), which enrolled 25,871 patients to test the two supplements in the prevention of cardiovascular disease and cancer.

Participants in this study – known as VITAL–Diabetic Kidney Disease, designed as an ancillary to VITAL – were assigned to one of four groups: vitamin D plus omega-3 fatty acids (n = 370), vitamin D plus placebo (n = 333), omega-3 fatty acids plus placebo (n = 289), or both placebos (n = 320). The goal was to assess changes in in glomerular filtration rate estimated from serum creatinine and cystatin C (eGFR) after 5 years.

Of the initial 1,312 participants, 934 (71%) finished the study. At 5-year follow-up, patients taking vitamin D had a mean change in eGFR of −12.3 mL/min per 1.73 m² (95% confidence interval, −13.4 to −11.2), compared with −13.1 mL/min per 1.73 m² (95% CI, −14.2 to −11.9) with placebo. Patients taking omega-3 fatty acids had a mean eGFR change of −12.2 mL/min per 1.73 m² (95% CI, −13.3 to −11.1), compared with −13.1 mL/min per 1.73 m² (95% CI, −14.2 to −12.0) with placebo.

The authors noted that the modest number of measurements collected per participant limited the evaluation and analyses. In addition, the study focused broadly on the type 2 diabetes population and not on subgroups, “who may derive more benefit from the study interventions.”

In an accompanying editorial, authors Anika Lucas, MD and Myles Wolf, MD, of Duke University in Durham, N.C., said multiple clinical trials, including this latest study from de Boer and colleagues on kidney function, have failed to reinforce the previously reported benefits of vitamin D.

“The VITAL-DKD study population had nearly normal mean 25-hydroxyvitamin D levels at baseline, leaving open the question of whether the results would have differed had recruitment been restricted to patients with moderate or severe vitamin D deficiency,” they wrote (JAMA. 2019 Nov 8. doi: 10.1001/jama.2019.17302).

Nevertheless, it seems safe to conclude that the previous associations between vitamin D deficiency and adverse health were “driven by unmeasured residual confounding or reverse causality.

“Without certainty about the ideal approach to vitamin D treatment in advanced CKD, a randomized trial that compared cholecalciferol, exogenous 25-hydroxyvitamin D, and an activated vitamin D analogue vs. placebo could definitively lay to rest multiple remaining questions in the area,” they suggested.

The National Institute of Diabetes and Digestive and Kidney Diseases funded the study. The authors reported numerous potential conflicts of interest, including receiving grants, consulting fees, and equipment and supplies from various pharmaceutical companies and the National Institutes of Health. Dr. Wolf reported having served as a consultant for Akebia, AMAG, Amgen, Ardelyx, Diasorin, and Pharmacosmos. No other disclosures were reported.

SOURCE: de Boer IH et al. JAMA. 2019 Nov 8. doi: 10.1001/jama.2019.17380.