ASN Kidney Week 2014

PHILADELPHIA – In patients with atrial fibrillation, declining kidney function significantly increased the risk of a major bleed during the first 30 days of warfarin therapy.

Those with the poorest kidney function had an 11-fold increase in the risk of a major bleed during that time, Min Jun, Ph.D., said at a meeting sponsored by the American Society of Nephrology. “After 30 days, the risk was attenuated, but it was still doubled,” compared with that of patients with normal kidney function.

Dr. Jun, a researcher at the University of Calgary (Alta.) retrospectively assessed bleeding incidence among 12,400 older adults with atrial fibrillation who started warfarin therapy from 2003 to 2010. He divided the cohort into six groups according to estimated glomerular filtration rates (eGFR), from normal (90 or more mL/min per 1.73 m²), to extremely poor (less than 15 mL/min per 1.73 m²).

The primary outcome was incident major bleeding (intracerebral, upper or lower gastrointestinal, or any other location). The analysis controlled for comorbidities, antiplatelet and nonsteroidal anti-inflammatory medications, and socioeconomic factors.

Almost 12% of the cohort experienced the primary outcome. The adjusted bleeding rates were highest for those with an eGFR of less than 15 mL/min per 1.73 m² (66 per 100 person-years) and lowest for those with an eGFR of at least 90 mL/min per 1.73 m² (5.9 per 100 person-years).

The rates moderated after the first 30 days of treatment, from 3.7 per 100 person-years in the highest eGFR group to 7.9 per 100 person-years in the lowest. But that was still a significant between-group difference.

The incidence ratio showed a clear, linear association with decreasing kidney function. During the first 30 days, it was highest in those patients with the lowest eGFR (11.08, compared with those with the highest eGFR). After 30 days, the ratio moderated; but it remained significantly elevated, compared with patients with the highest eGFR, at 2.09.

Kidney function apparently also influenced gastrointestinal bleeding, Dr. Jun noted. GI bleeding occurred in about 6% of those patients with an eGFR of at least 90 mL/min per 1.73 m², but in almost 19% of patients with an eGFR of less than 15 mL/min per 1.73 m². Intracranial bleeds occurred in less than 1% of patients in each group. There were no significant findings in other bleeding types, which were increased in the first 30 days of treatment, but which never exceeded 5% in any group.

Dr. Jun had no financial disclosures.

msullivan@frontlinemedcom.com

PHILADELPHIA – In patients with atrial fibrillation, declining kidney function significantly increased the risk of a major bleed during the first 30 days of warfarin therapy.

Those with the poorest kidney function had an 11-fold increase in the risk of a major bleed during that time, Min Jun, Ph.D., said at a meeting sponsored by the American Society of Nephrology. “After 30 days, the risk was attenuated, but it was still doubled,” compared with that of patients with normal kidney function.

Dr. Jun, a researcher at the University of Calgary (Alta.) retrospectively assessed bleeding incidence among 12,400 older adults with atrial fibrillation who started warfarin therapy from 2003 to 2010. He divided the cohort into six groups according to estimated glomerular filtration rates (eGFR), from normal (90 or more mL/min per 1.73 m²), to extremely poor (less than 15 mL/min per 1.73 m²).

The primary outcome was incident major bleeding (intracerebral, upper or lower gastrointestinal, or any other location). The analysis controlled for comorbidities, antiplatelet and nonsteroidal anti-inflammatory medications, and socioeconomic factors.

Almost 12% of the cohort experienced the primary outcome. The adjusted bleeding rates were highest for those with an eGFR of less than 15 mL/min per 1.73 m² (66 per 100 person-years) and lowest for those with an eGFR of at least 90 mL/min per 1.73 m² (5.9 per 100 person-years).

The rates moderated after the first 30 days of treatment, from 3.7 per 100 person-years in the highest eGFR group to 7.9 per 100 person-years in the lowest. But that was still a significant between-group difference.

The incidence ratio showed a clear, linear association with decreasing kidney function. During the first 30 days, it was highest in those patients with the lowest eGFR (11.08, compared with those with the highest eGFR). After 30 days, the ratio moderated; but it remained significantly elevated, compared with patients with the highest eGFR, at 2.09.

Kidney function apparently also influenced gastrointestinal bleeding, Dr. Jun noted. GI bleeding occurred in about 6% of those patients with an eGFR of at least 90 mL/min per 1.73 m², but in almost 19% of patients with an eGFR of less than 15 mL/min per 1.73 m². Intracranial bleeds occurred in less than 1% of patients in each group. There were no significant findings in other bleeding types, which were increased in the first 30 days of treatment, but which never exceeded 5% in any group.

Dr. Jun had no financial disclosures.

msullivan@frontlinemedcom.com

PHILADELPHIA – In patients with atrial fibrillation, declining kidney function significantly increased the risk of a major bleed during the first 30 days of warfarin therapy.

Those with the poorest kidney function had an 11-fold increase in the risk of a major bleed during that time, Min Jun, Ph.D., said at a meeting sponsored by the American Society of Nephrology. “After 30 days, the risk was attenuated, but it was still doubled,” compared with that of patients with normal kidney function.

Dr. Jun, a researcher at the University of Calgary (Alta.) retrospectively assessed bleeding incidence among 12,400 older adults with atrial fibrillation who started warfarin therapy from 2003 to 2010. He divided the cohort into six groups according to estimated glomerular filtration rates (eGFR), from normal (90 or more mL/min per 1.73 m²), to extremely poor (less than 15 mL/min per 1.73 m²).

The primary outcome was incident major bleeding (intracerebral, upper or lower gastrointestinal, or any other location). The analysis controlled for comorbidities, antiplatelet and nonsteroidal anti-inflammatory medications, and socioeconomic factors.

Almost 12% of the cohort experienced the primary outcome. The adjusted bleeding rates were highest for those with an eGFR of less than 15 mL/min per 1.73 m² (66 per 100 person-years) and lowest for those with an eGFR of at least 90 mL/min per 1.73 m² (5.9 per 100 person-years).

The rates moderated after the first 30 days of treatment, from 3.7 per 100 person-years in the highest eGFR group to 7.9 per 100 person-years in the lowest. But that was still a significant between-group difference.

The incidence ratio showed a clear, linear association with decreasing kidney function. During the first 30 days, it was highest in those patients with the lowest eGFR (11.08, compared with those with the highest eGFR). After 30 days, the ratio moderated; but it remained significantly elevated, compared with patients with the highest eGFR, at 2.09.

Kidney function apparently also influenced gastrointestinal bleeding, Dr. Jun noted. GI bleeding occurred in about 6% of those patients with an eGFR of at least 90 mL/min per 1.73 m², but in almost 19% of patients with an eGFR of less than 15 mL/min per 1.73 m². Intracranial bleeds occurred in less than 1% of patients in each group. There were no significant findings in other bleeding types, which were increased in the first 30 days of treatment, but which never exceeded 5% in any group.

Dr. Jun had no financial disclosures.

msullivan@frontlinemedcom.com

PHILADELPHIA– Anti-TGF-beta 1 therapy was safe and well-tolerated, but failed to slow disease progression in patients with advanced diabetic nephropathy in a randomized, double-masked, phase 2 dose-ranging study.

In fact, the trial was terminated 4 months early for efficacy futility, Dr. James R. Voelker reported at Kidney Week 2014.

In 416 patients with type 1 or type 2 diabetes and a likelihood of rapid disease progression who were randomized to receive subcutaneous treatment with either placebo or various doses of a beta-1-specific humanized monoclonal neutralizing antibody known as LY2382770 (LY).

Treatment at any dose was not significantly more effective than placebo with respect to the primary outcome measure of mean change in serum creatinine. Mean serum creatinine increased from 2.22 to 2.48 mg/dl in the placebo group, and in the treatment groups it increased from 2.15 to 2.49 mg/dl (2 mg/month group), from 2.13 to 2.49 mg/dl (10 mg/month group), and from 2.15 to 2.50 mg/dl (50 mg/month group), Dr. Voelker of Eli Lilly and Co., Indianapolis, said at the meeting, which was sponsored by the American Society of Nephrology.

Patients in the study were adults aged 25 years or older (mean 62.2 years ) with serum creatinine of 1.3 to 3.3 mg/dl for women, and 1.5 to 3.5 mg/dl for men, or estimated glomerular filtration rate of 20 to 60 ml/min/1.73 m², and they had a 24-hour urine protein/creatinine ratio of at least 800 mg/g. The groups were similar with respect to demographics and baseline characteristic, and most (75%) were men with type 2 diabetes (90%). All patient were receiving stable renin-angiotensin-system inhibition (RASi) therapy.

The intent was to select a population with a likelihood of fairly rapid disease progression during the course of the study to enable detection of a treatment effect, Dr. Voelker explained.

“Diabetic nephropathy is a disease of significant unmet medical need, as it is the leading cause of end-stage renal disease in much of the world. Thus. it is incumbent upon the nephrology community to identify new and more effective treatments than are currently available,” Dr. Voelker said.

TGF-beta over-activity has been implicated as a key pathogenic factor in diabetic neuropathy, and it was previously demonstrated that a TGF-beta 1-specific humanized monoclonal antibody was as effective as an antibody against all three TGF-beta isoforms, he said.

“We also had demonstrated that beta 1-specific inhibition in preclinical animal toxicology testing was far more tolerated than when you inhibit all 3 TGF-beta isoforms, which I should mention are all differentially expressed and regulated, but all signal through the same receptor complex,” he added, noting that based on these and other data, it was hypothesized that modulating excessive beta 1 activity with LY would safely slow renal progression in patients with diabetes on background RASi therapy.

The study was overseen by an independent data safety monitoring committee that reviewed unblinded safety data at periodic intervals. No safety issues emerged, but in the later stages of the study the committee did recommend that an unscheduled utility analysis be performed. Based on the results of that analysis, the decision was made to prematurely terminate the study about 4 months before its scheduled completion.

“Unfortunately there was no evidence in any of the study arms of a slowing of the rate of (serum creatinine increase),” Dr. Voelker said, adding that there also was no evidence of a benefit in numerous subgroup analyses, including analyses based on diabetes type.

Dr. Voelker is an employee of Eli Lilly and Co, which sponsored this study.

PHILADELPHIA– Anti-TGF-beta 1 therapy was safe and well-tolerated, but failed to slow disease progression in patients with advanced diabetic nephropathy in a randomized, double-masked, phase 2 dose-ranging study.

In fact, the trial was terminated 4 months early for efficacy futility, Dr. James R. Voelker reported at Kidney Week 2014.

In 416 patients with type 1 or type 2 diabetes and a likelihood of rapid disease progression who were randomized to receive subcutaneous treatment with either placebo or various doses of a beta-1-specific humanized monoclonal neutralizing antibody known as LY2382770 (LY).

Treatment at any dose was not significantly more effective than placebo with respect to the primary outcome measure of mean change in serum creatinine. Mean serum creatinine increased from 2.22 to 2.48 mg/dl in the placebo group, and in the treatment groups it increased from 2.15 to 2.49 mg/dl (2 mg/month group), from 2.13 to 2.49 mg/dl (10 mg/month group), and from 2.15 to 2.50 mg/dl (50 mg/month group), Dr. Voelker of Eli Lilly and Co., Indianapolis, said at the meeting, which was sponsored by the American Society of Nephrology.

Patients in the study were adults aged 25 years or older (mean 62.2 years ) with serum creatinine of 1.3 to 3.3 mg/dl for women, and 1.5 to 3.5 mg/dl for men, or estimated glomerular filtration rate of 20 to 60 ml/min/1.73 m², and they had a 24-hour urine protein/creatinine ratio of at least 800 mg/g. The groups were similar with respect to demographics and baseline characteristic, and most (75%) were men with type 2 diabetes (90%). All patient were receiving stable renin-angiotensin-system inhibition (RASi) therapy.

The intent was to select a population with a likelihood of fairly rapid disease progression during the course of the study to enable detection of a treatment effect, Dr. Voelker explained.

“Diabetic nephropathy is a disease of significant unmet medical need, as it is the leading cause of end-stage renal disease in much of the world. Thus. it is incumbent upon the nephrology community to identify new and more effective treatments than are currently available,” Dr. Voelker said.

TGF-beta over-activity has been implicated as a key pathogenic factor in diabetic neuropathy, and it was previously demonstrated that a TGF-beta 1-specific humanized monoclonal antibody was as effective as an antibody against all three TGF-beta isoforms, he said.

“We also had demonstrated that beta 1-specific inhibition in preclinical animal toxicology testing was far more tolerated than when you inhibit all 3 TGF-beta isoforms, which I should mention are all differentially expressed and regulated, but all signal through the same receptor complex,” he added, noting that based on these and other data, it was hypothesized that modulating excessive beta 1 activity with LY would safely slow renal progression in patients with diabetes on background RASi therapy.

The study was overseen by an independent data safety monitoring committee that reviewed unblinded safety data at periodic intervals. No safety issues emerged, but in the later stages of the study the committee did recommend that an unscheduled utility analysis be performed. Based on the results of that analysis, the decision was made to prematurely terminate the study about 4 months before its scheduled completion.

“Unfortunately there was no evidence in any of the study arms of a slowing of the rate of (serum creatinine increase),” Dr. Voelker said, adding that there also was no evidence of a benefit in numerous subgroup analyses, including analyses based on diabetes type.

Dr. Voelker is an employee of Eli Lilly and Co, which sponsored this study.

PHILADELPHIA– Anti-TGF-beta 1 therapy was safe and well-tolerated, but failed to slow disease progression in patients with advanced diabetic nephropathy in a randomized, double-masked, phase 2 dose-ranging study.

In fact, the trial was terminated 4 months early for efficacy futility, Dr. James R. Voelker reported at Kidney Week 2014.

In 416 patients with type 1 or type 2 diabetes and a likelihood of rapid disease progression who were randomized to receive subcutaneous treatment with either placebo or various doses of a beta-1-specific humanized monoclonal neutralizing antibody known as LY2382770 (LY).

Treatment at any dose was not significantly more effective than placebo with respect to the primary outcome measure of mean change in serum creatinine. Mean serum creatinine increased from 2.22 to 2.48 mg/dl in the placebo group, and in the treatment groups it increased from 2.15 to 2.49 mg/dl (2 mg/month group), from 2.13 to 2.49 mg/dl (10 mg/month group), and from 2.15 to 2.50 mg/dl (50 mg/month group), Dr. Voelker of Eli Lilly and Co., Indianapolis, said at the meeting, which was sponsored by the American Society of Nephrology.

Patients in the study were adults aged 25 years or older (mean 62.2 years ) with serum creatinine of 1.3 to 3.3 mg/dl for women, and 1.5 to 3.5 mg/dl for men, or estimated glomerular filtration rate of 20 to 60 ml/min/1.73 m², and they had a 24-hour urine protein/creatinine ratio of at least 800 mg/g. The groups were similar with respect to demographics and baseline characteristic, and most (75%) were men with type 2 diabetes (90%). All patient were receiving stable renin-angiotensin-system inhibition (RASi) therapy.

The intent was to select a population with a likelihood of fairly rapid disease progression during the course of the study to enable detection of a treatment effect, Dr. Voelker explained.

“Diabetic nephropathy is a disease of significant unmet medical need, as it is the leading cause of end-stage renal disease in much of the world. Thus. it is incumbent upon the nephrology community to identify new and more effective treatments than are currently available,” Dr. Voelker said.

TGF-beta over-activity has been implicated as a key pathogenic factor in diabetic neuropathy, and it was previously demonstrated that a TGF-beta 1-specific humanized monoclonal antibody was as effective as an antibody against all three TGF-beta isoforms, he said.

“We also had demonstrated that beta 1-specific inhibition in preclinical animal toxicology testing was far more tolerated than when you inhibit all 3 TGF-beta isoforms, which I should mention are all differentially expressed and regulated, but all signal through the same receptor complex,” he added, noting that based on these and other data, it was hypothesized that modulating excessive beta 1 activity with LY would safely slow renal progression in patients with diabetes on background RASi therapy.

The study was overseen by an independent data safety monitoring committee that reviewed unblinded safety data at periodic intervals. No safety issues emerged, but in the later stages of the study the committee did recommend that an unscheduled utility analysis be performed. Based on the results of that analysis, the decision was made to prematurely terminate the study about 4 months before its scheduled completion.

“Unfortunately there was no evidence in any of the study arms of a slowing of the rate of (serum creatinine increase),” Dr. Voelker said, adding that there also was no evidence of a benefit in numerous subgroup analyses, including analyses based on diabetes type.

Dr. Voelker is an employee of Eli Lilly and Co, which sponsored this study.

PHILADELPHIA – Dual blockade of the renin-angiotensin-aldosterone system with combined angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy was no more effective than ACE inhibitor therapy alone for slowing the rate of increase in total kidney volume in patients with early autosomal dominant polycystic kidney disease, investigators have reported.

Notably, though, aggressive blood pressure control, as compared with standard control, was associated with a slower rate of increase in total kidney volume in study A of the Halt Progression of Polycystic Kidney Disease (HALT-PKD) trial, Dr. Arlene B. Chapman reported at Kidney Week 2014.

Participants in the randomized, placebo-controlled 2x2 factorial trial were 423 hypertensive patients aged 15 to 49 years who had an estimated glomerular filtration rate (eGFR) of greater than 60 ml/min/1.73 m² of body surface area. They were enrolled at 7 sites from February 2000 through June 2009, underwent a 2-4 week washout period during which antihypertensive therapy was discontinued and clonidine and labetalol therapy was maintained, and were randomized to receive either lisinopril plus telmisartan, or lisinopril plus placebo. They were also randomized to a standard blood pressure target of 120/70 to 130/80 mm Hg, or to a low blood pressure target of 95/60 to 110/75 mm Hg. Treatment doses were adjusted to achieve the target blood pressure, said Dr. Chapman of Emory University, Atlanta.

With respect to dual blockade of the renin-angiotensin-aldosterone system (RAAS) and the primary outcome of percentage change in total kidney volume over time, the rate of total kidney volume increase was similar at 6.0% and 6.2% per year in the lisinopril plus telmisartan group and the lisinopril plus placebo group, respectively, according to findings simultaneously published online Nov. 15 in the New England Journal of Medicine, which showed that total kidney volume increased by 40.5% and 42.2% at 60 months in the groups, respectively (N Engl J Med 2014 Nov. 15[doi:10.1056/NEJMoa1402685])

With respect to the standard vs. low blood pressure target, which was the focus of Dr. Chapman’s talk, significant differences were seen in systolic and diastolic blood pressure, with a difference of 13.4 mm Hg and 9.3 mm Hg, respectively, between the groups at the end of the trial, she said.

“Urinary aldosterone levels decreased significantly in both groups. However, there were no differences in the levels of change between the low and standard blood pressure groups,” she said.

The low target group had a 14.2% slower annual increase in total kidney volume at the end of the study as compared with those in the standard blood pressure target group (annualized change of 5.57% in the low target group vs. 6.57% in the standard target group), she said.

Overall, the change in eGFR did not differ between the groups. Urinary albumin excretion and left ventricular mass declined significantly more in the low vs. standard blood pressure control group, and renal vascular resistance remained the same in the low blood pressure control group, but increased in the standard blood pressure control group.

During a mean follow-up of 5 years, no differences were seen between the groups in the rate of hyperkalemia, acute kidney injury, hospitalizations, cardiac-related hospitalizations or mortality, and the event rates were low, she noted.

“Polycystic kidney disease is the fourth leading cause of renal failure in the United States. It is characterized by renal cyst growth with increased total kidney volume, resulting in activation of the renin-angiotensin system, the development of hypertension early, and progression to renal failure. To date there is no evidence that blood pressure control or blockade of the renin-angiotensin-system slows the progression of renal disease,” she said.

This portion of the HALT-PKD trial showed that both dual blockade of the RAAS and rigorous blood pressure control were safe, but that dual blockade provides no benefit as compared with lisinopril monotherapy with regard to change in total kidney volume and eGFR.

Aggressive blood pressure control, however, was of benefit.

“Low blood pressure treatment in young, healthy, hypertensive polycystic kidney disease patients with blockade of the renin-angiotensin-system was well-tolerated and safe and resulted in a 14.2% slower rate of total kidney volume growth over 5 years, reduced left ventricular mass index, urinary albumin secretion, and renal vascular resistance. This is without impact overall on the change in kidney function,” she concluded.

The HALT-PKD trial was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (including a grant to Dr. Chapman), the National Center for Research Resources General Clinical Research Centers, the National Center for Advancing Translational Sciences Clinical and Translational Science Awards, the Zell Family Foundation, and the PKD Foundation. Detailed author disclosures are available with the full text of the HALT-PKD study at NEJM.org.

PHILADELPHIA – Dual blockade of the renin-angiotensin-aldosterone system with combined angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy was no more effective than ACE inhibitor therapy alone for slowing the rate of increase in total kidney volume in patients with early autosomal dominant polycystic kidney disease, investigators have reported.

Notably, though, aggressive blood pressure control, as compared with standard control, was associated with a slower rate of increase in total kidney volume in study A of the Halt Progression of Polycystic Kidney Disease (HALT-PKD) trial, Dr. Arlene B. Chapman reported at Kidney Week 2014.

Participants in the randomized, placebo-controlled 2x2 factorial trial were 423 hypertensive patients aged 15 to 49 years who had an estimated glomerular filtration rate (eGFR) of greater than 60 ml/min/1.73 m² of body surface area. They were enrolled at 7 sites from February 2000 through June 2009, underwent a 2-4 week washout period during which antihypertensive therapy was discontinued and clonidine and labetalol therapy was maintained, and were randomized to receive either lisinopril plus telmisartan, or lisinopril plus placebo. They were also randomized to a standard blood pressure target of 120/70 to 130/80 mm Hg, or to a low blood pressure target of 95/60 to 110/75 mm Hg. Treatment doses were adjusted to achieve the target blood pressure, said Dr. Chapman of Emory University, Atlanta.

With respect to dual blockade of the renin-angiotensin-aldosterone system (RAAS) and the primary outcome of percentage change in total kidney volume over time, the rate of total kidney volume increase was similar at 6.0% and 6.2% per year in the lisinopril plus telmisartan group and the lisinopril plus placebo group, respectively, according to findings simultaneously published online Nov. 15 in the New England Journal of Medicine, which showed that total kidney volume increased by 40.5% and 42.2% at 60 months in the groups, respectively (N Engl J Med 2014 Nov. 15[doi:10.1056/NEJMoa1402685])

With respect to the standard vs. low blood pressure target, which was the focus of Dr. Chapman’s talk, significant differences were seen in systolic and diastolic blood pressure, with a difference of 13.4 mm Hg and 9.3 mm Hg, respectively, between the groups at the end of the trial, she said.

“Urinary aldosterone levels decreased significantly in both groups. However, there were no differences in the levels of change between the low and standard blood pressure groups,” she said.

The low target group had a 14.2% slower annual increase in total kidney volume at the end of the study as compared with those in the standard blood pressure target group (annualized change of 5.57% in the low target group vs. 6.57% in the standard target group), she said.

Overall, the change in eGFR did not differ between the groups. Urinary albumin excretion and left ventricular mass declined significantly more in the low vs. standard blood pressure control group, and renal vascular resistance remained the same in the low blood pressure control group, but increased in the standard blood pressure control group.

During a mean follow-up of 5 years, no differences were seen between the groups in the rate of hyperkalemia, acute kidney injury, hospitalizations, cardiac-related hospitalizations or mortality, and the event rates were low, she noted.

“Polycystic kidney disease is the fourth leading cause of renal failure in the United States. It is characterized by renal cyst growth with increased total kidney volume, resulting in activation of the renin-angiotensin system, the development of hypertension early, and progression to renal failure. To date there is no evidence that blood pressure control or blockade of the renin-angiotensin-system slows the progression of renal disease,” she said.

This portion of the HALT-PKD trial showed that both dual blockade of the RAAS and rigorous blood pressure control were safe, but that dual blockade provides no benefit as compared with lisinopril monotherapy with regard to change in total kidney volume and eGFR.

Aggressive blood pressure control, however, was of benefit.

“Low blood pressure treatment in young, healthy, hypertensive polycystic kidney disease patients with blockade of the renin-angiotensin-system was well-tolerated and safe and resulted in a 14.2% slower rate of total kidney volume growth over 5 years, reduced left ventricular mass index, urinary albumin secretion, and renal vascular resistance. This is without impact overall on the change in kidney function,” she concluded.

The HALT-PKD trial was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (including a grant to Dr. Chapman), the National Center for Research Resources General Clinical Research Centers, the National Center for Advancing Translational Sciences Clinical and Translational Science Awards, the Zell Family Foundation, and the PKD Foundation. Detailed author disclosures are available with the full text of the HALT-PKD study at NEJM.org.

PHILADELPHIA – Dual blockade of the renin-angiotensin-aldosterone system with combined angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy was no more effective than ACE inhibitor therapy alone for slowing the rate of increase in total kidney volume in patients with early autosomal dominant polycystic kidney disease, investigators have reported.

Notably, though, aggressive blood pressure control, as compared with standard control, was associated with a slower rate of increase in total kidney volume in study A of the Halt Progression of Polycystic Kidney Disease (HALT-PKD) trial, Dr. Arlene B. Chapman reported at Kidney Week 2014.

Participants in the randomized, placebo-controlled 2x2 factorial trial were 423 hypertensive patients aged 15 to 49 years who had an estimated glomerular filtration rate (eGFR) of greater than 60 ml/min/1.73 m² of body surface area. They were enrolled at 7 sites from February 2000 through June 2009, underwent a 2-4 week washout period during which antihypertensive therapy was discontinued and clonidine and labetalol therapy was maintained, and were randomized to receive either lisinopril plus telmisartan, or lisinopril plus placebo. They were also randomized to a standard blood pressure target of 120/70 to 130/80 mm Hg, or to a low blood pressure target of 95/60 to 110/75 mm Hg. Treatment doses were adjusted to achieve the target blood pressure, said Dr. Chapman of Emory University, Atlanta.

With respect to dual blockade of the renin-angiotensin-aldosterone system (RAAS) and the primary outcome of percentage change in total kidney volume over time, the rate of total kidney volume increase was similar at 6.0% and 6.2% per year in the lisinopril plus telmisartan group and the lisinopril plus placebo group, respectively, according to findings simultaneously published online Nov. 15 in the New England Journal of Medicine, which showed that total kidney volume increased by 40.5% and 42.2% at 60 months in the groups, respectively (N Engl J Med 2014 Nov. 15[doi:10.1056/NEJMoa1402685])

With respect to the standard vs. low blood pressure target, which was the focus of Dr. Chapman’s talk, significant differences were seen in systolic and diastolic blood pressure, with a difference of 13.4 mm Hg and 9.3 mm Hg, respectively, between the groups at the end of the trial, she said.

“Urinary aldosterone levels decreased significantly in both groups. However, there were no differences in the levels of change between the low and standard blood pressure groups,” she said.

The low target group had a 14.2% slower annual increase in total kidney volume at the end of the study as compared with those in the standard blood pressure target group (annualized change of 5.57% in the low target group vs. 6.57% in the standard target group), she said.

Overall, the change in eGFR did not differ between the groups. Urinary albumin excretion and left ventricular mass declined significantly more in the low vs. standard blood pressure control group, and renal vascular resistance remained the same in the low blood pressure control group, but increased in the standard blood pressure control group.

During a mean follow-up of 5 years, no differences were seen between the groups in the rate of hyperkalemia, acute kidney injury, hospitalizations, cardiac-related hospitalizations or mortality, and the event rates were low, she noted.

“Polycystic kidney disease is the fourth leading cause of renal failure in the United States. It is characterized by renal cyst growth with increased total kidney volume, resulting in activation of the renin-angiotensin system, the development of hypertension early, and progression to renal failure. To date there is no evidence that blood pressure control or blockade of the renin-angiotensin-system slows the progression of renal disease,” she said.

This portion of the HALT-PKD trial showed that both dual blockade of the RAAS and rigorous blood pressure control were safe, but that dual blockade provides no benefit as compared with lisinopril monotherapy with regard to change in total kidney volume and eGFR.

Aggressive blood pressure control, however, was of benefit.

“Low blood pressure treatment in young, healthy, hypertensive polycystic kidney disease patients with blockade of the renin-angiotensin-system was well-tolerated and safe and resulted in a 14.2% slower rate of total kidney volume growth over 5 years, reduced left ventricular mass index, urinary albumin secretion, and renal vascular resistance. This is without impact overall on the change in kidney function,” she concluded.

The HALT-PKD trial was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (including a grant to Dr. Chapman), the National Center for Research Resources General Clinical Research Centers, the National Center for Advancing Translational Sciences Clinical and Translational Science Awards, the Zell Family Foundation, and the PKD Foundation. Detailed author disclosures are available with the full text of the HALT-PKD study at NEJM.org.

philadelphia – Treatment with ergocalciferol (vitamin D2) normalized circulating 25-hydroxyvitamin D levels within 3 months in hemodialysis patients with 25-hydroxyvitamin D deficiency, but this did not translate to clinical benefit with respect to a number of measures in a 6-month randomized, double-blind, placebo-controlled trial.

Levels of 25-hydroxyvitamin D in 276 hemodialysis patients with vitamin D deficiency who were randomized to receive either ergocalciferol treatment for 6 months or placebo were 16.0 vs. 16.9 ng/ml at baseline, 41.0 vs. 17.3 ng/ml at 3 months, and 39.2 vs. 17.5 ng/ml at 6 months, respectively, Dr. Dana Miskulin reported at Kidney Week 2014.

Parathyroid hormone (PTH) level was the only measure that showed a significant difference between the placebo and treatment groups. PTH levels dropped with treatment at 6 months (decreasing from 475 pg/ml at baseline to 450 pg/ml), but levels rose in the placebo group (440 to 505 pg/ml). No significant differences were seen at 6 months between the two groups in the primary outcomes measure of Epoetin alfa (Epogen) dose (5,400 vs. 5,800 units per week at baseline and 6,100 vs. 7,000 units/week at 6 months in the groups, respectively). There also were no differences between the groups in calcium levels, phosphorus levels, C-reactive protein levels, 1,25-dihydroxyvitamin D dose, cinacalcet dose, infection rate, or all-cause or infection-related hospitalization, Dr. Miskulin of Tufts Medical Center, Boston said at the meeting, which was sponsored by the American Society of Nephrology.

Study participants had a mean age of 61 years, median dialysis vintage of 3.5 years, and 25-hydroxyvitamin D levels less than 30 ng/ml. A majority (60%) were back, 45% were women, and 46% had diabetes as the cause of end stage renal disease. The treatment and placebo groups were similar with respect to clinical factors at baseline.

Treatment was given at 50,000 IU weekly for 6 months in patients with 25-hydroxyvitamin D levels less than 16 ng/ml and 50,000 IU weekly for 3 months followed by 50,000 IU monthly for 3 months in those with levels of 16-30 ng/ml, she said.

Vitamin D deficiency has been linked to numerous health problems, including cardiovascular events and mortality, infections, immune disorders, diabetes, cancers, and skin diseases, and about 80% of dialysis patients have 25-hydroxyvitamin D levels less than 30 ng/ml, Dr. Miskulin said.

The current findings suggest that while supplementation with at least 50,000 units of ergocalciferol every 2 weeks achieves and maintains vitamin D levels greater than 30 ng/ml without hypercalcemia or hyperphosphatemia in most hemodialysis patients, the benefits of supplementation are questionable. Although she agreed that without clinical benefit there is no need to provide supplementation, she also acknowledged that longer follow-up is needed to determine the effects of vitamin D supplementation.

This study was funded by Dialysis Clinic, Inc. Dr. Miskulin reported having no disclosures.

philadelphia – Treatment with ergocalciferol (vitamin D2) normalized circulating 25-hydroxyvitamin D levels within 3 months in hemodialysis patients with 25-hydroxyvitamin D deficiency, but this did not translate to clinical benefit with respect to a number of measures in a 6-month randomized, double-blind, placebo-controlled trial.

Levels of 25-hydroxyvitamin D in 276 hemodialysis patients with vitamin D deficiency who were randomized to receive either ergocalciferol treatment for 6 months or placebo were 16.0 vs. 16.9 ng/ml at baseline, 41.0 vs. 17.3 ng/ml at 3 months, and 39.2 vs. 17.5 ng/ml at 6 months, respectively, Dr. Dana Miskulin reported at Kidney Week 2014.

Parathyroid hormone (PTH) level was the only measure that showed a significant difference between the placebo and treatment groups. PTH levels dropped with treatment at 6 months (decreasing from 475 pg/ml at baseline to 450 pg/ml), but levels rose in the placebo group (440 to 505 pg/ml). No significant differences were seen at 6 months between the two groups in the primary outcomes measure of Epoetin alfa (Epogen) dose (5,400 vs. 5,800 units per week at baseline and 6,100 vs. 7,000 units/week at 6 months in the groups, respectively). There also were no differences between the groups in calcium levels, phosphorus levels, C-reactive protein levels, 1,25-dihydroxyvitamin D dose, cinacalcet dose, infection rate, or all-cause or infection-related hospitalization, Dr. Miskulin of Tufts Medical Center, Boston said at the meeting, which was sponsored by the American Society of Nephrology.

Study participants had a mean age of 61 years, median dialysis vintage of 3.5 years, and 25-hydroxyvitamin D levels less than 30 ng/ml. A majority (60%) were back, 45% were women, and 46% had diabetes as the cause of end stage renal disease. The treatment and placebo groups were similar with respect to clinical factors at baseline.

Treatment was given at 50,000 IU weekly for 6 months in patients with 25-hydroxyvitamin D levels less than 16 ng/ml and 50,000 IU weekly for 3 months followed by 50,000 IU monthly for 3 months in those with levels of 16-30 ng/ml, she said.

Vitamin D deficiency has been linked to numerous health problems, including cardiovascular events and mortality, infections, immune disorders, diabetes, cancers, and skin diseases, and about 80% of dialysis patients have 25-hydroxyvitamin D levels less than 30 ng/ml, Dr. Miskulin said.

The current findings suggest that while supplementation with at least 50,000 units of ergocalciferol every 2 weeks achieves and maintains vitamin D levels greater than 30 ng/ml without hypercalcemia or hyperphosphatemia in most hemodialysis patients, the benefits of supplementation are questionable. Although she agreed that without clinical benefit there is no need to provide supplementation, she also acknowledged that longer follow-up is needed to determine the effects of vitamin D supplementation.

This study was funded by Dialysis Clinic, Inc. Dr. Miskulin reported having no disclosures.

philadelphia – Treatment with ergocalciferol (vitamin D2) normalized circulating 25-hydroxyvitamin D levels within 3 months in hemodialysis patients with 25-hydroxyvitamin D deficiency, but this did not translate to clinical benefit with respect to a number of measures in a 6-month randomized, double-blind, placebo-controlled trial.

Levels of 25-hydroxyvitamin D in 276 hemodialysis patients with vitamin D deficiency who were randomized to receive either ergocalciferol treatment for 6 months or placebo were 16.0 vs. 16.9 ng/ml at baseline, 41.0 vs. 17.3 ng/ml at 3 months, and 39.2 vs. 17.5 ng/ml at 6 months, respectively, Dr. Dana Miskulin reported at Kidney Week 2014.

Parathyroid hormone (PTH) level was the only measure that showed a significant difference between the placebo and treatment groups. PTH levels dropped with treatment at 6 months (decreasing from 475 pg/ml at baseline to 450 pg/ml), but levels rose in the placebo group (440 to 505 pg/ml). No significant differences were seen at 6 months between the two groups in the primary outcomes measure of Epoetin alfa (Epogen) dose (5,400 vs. 5,800 units per week at baseline and 6,100 vs. 7,000 units/week at 6 months in the groups, respectively). There also were no differences between the groups in calcium levels, phosphorus levels, C-reactive protein levels, 1,25-dihydroxyvitamin D dose, cinacalcet dose, infection rate, or all-cause or infection-related hospitalization, Dr. Miskulin of Tufts Medical Center, Boston said at the meeting, which was sponsored by the American Society of Nephrology.

Study participants had a mean age of 61 years, median dialysis vintage of 3.5 years, and 25-hydroxyvitamin D levels less than 30 ng/ml. A majority (60%) were back, 45% were women, and 46% had diabetes as the cause of end stage renal disease. The treatment and placebo groups were similar with respect to clinical factors at baseline.

Treatment was given at 50,000 IU weekly for 6 months in patients with 25-hydroxyvitamin D levels less than 16 ng/ml and 50,000 IU weekly for 3 months followed by 50,000 IU monthly for 3 months in those with levels of 16-30 ng/ml, she said.

Vitamin D deficiency has been linked to numerous health problems, including cardiovascular events and mortality, infections, immune disorders, diabetes, cancers, and skin diseases, and about 80% of dialysis patients have 25-hydroxyvitamin D levels less than 30 ng/ml, Dr. Miskulin said.

The current findings suggest that while supplementation with at least 50,000 units of ergocalciferol every 2 weeks achieves and maintains vitamin D levels greater than 30 ng/ml without hypercalcemia or hyperphosphatemia in most hemodialysis patients, the benefits of supplementation are questionable. Although she agreed that without clinical benefit there is no need to provide supplementation, she also acknowledged that longer follow-up is needed to determine the effects of vitamin D supplementation.

This study was funded by Dialysis Clinic, Inc. Dr. Miskulin reported having no disclosures.

PHILADELPHIA – Patients with type 2 diabetes, chronic kidney disease, and a high risk of obstructive sleep apnea have more rapid loss of kidney function than do similar patients with a low risk of sleep apnea, findings from a retrospective cohort study suggest.

Of 56 patients with diabetic nephropathy who underwent screening for obstructive sleep apnea, 34 (61%) were at high risk. Compared with 22 patients with a low risk score, the high-risk patients had a significantly greater loss of estimated glomerular filtration rate over time (median loss of -3.4 vs. 1.5 ml/min/1.73 m² per year for the high- vs. low-risk patients, respectively), Dr. Roberto Pisoni reported in a poster at the annual meeting of the American Society of Nephrology.

This finding was despite comparable blood pressure for the high- and low-risk groups (systolic: 141.7 and 143.7 mm Hg; diastolic: 72.0 and 72.4 mm Hg, respectively), proteinuria upon admission to a chronic kidney disease clinic (urinary protein/creatinine ratio, 1.9 and 1.6 g/g, respectively), and time spent in clinic (1.9 vs. 2.1 years, respectively), said Dr. Pisoni of the Medical University of South Carolina, Charleston.

Patients in the high- and low-risk groups also had similar baseline gender, body mass index, use of renin-angiotensin-aldosterone system blockers, eGFR, and co-morbidities, he noted.

Data used for this study were from the University of Alabama at Birmingham Chronic Kidney Disease Database. Patients had completed the Berlin questionnaire to assess for sleep apnea during a 9-month study period.

Obstructive sleep apnea is common in patients with type 2 diabetes and is also associated with glomerular hyperfiltration and proteinuria in patients with normal renal function, which raised the question of whether it might be related to chronic kidney disease progression, Dr. Pisoni explained. He noted that the association between obstructive sleep apnea and diabetic nephropathy has not been fully investigated.

The study demonstrated that the “simple approach” of assessing obstructive sleep apnea risk identifies patients who are also at increased risk of CKD progression, he said, adding that the findings require replication in a prospective cohort.

Dr. Pisoni reported having no disclosures.

PHILADELPHIA – Patients with type 2 diabetes, chronic kidney disease, and a high risk of obstructive sleep apnea have more rapid loss of kidney function than do similar patients with a low risk of sleep apnea, findings from a retrospective cohort study suggest.

Of 56 patients with diabetic nephropathy who underwent screening for obstructive sleep apnea, 34 (61%) were at high risk. Compared with 22 patients with a low risk score, the high-risk patients had a significantly greater loss of estimated glomerular filtration rate over time (median loss of -3.4 vs. 1.5 ml/min/1.73 m² per year for the high- vs. low-risk patients, respectively), Dr. Roberto Pisoni reported in a poster at the annual meeting of the American Society of Nephrology.

This finding was despite comparable blood pressure for the high- and low-risk groups (systolic: 141.7 and 143.7 mm Hg; diastolic: 72.0 and 72.4 mm Hg, respectively), proteinuria upon admission to a chronic kidney disease clinic (urinary protein/creatinine ratio, 1.9 and 1.6 g/g, respectively), and time spent in clinic (1.9 vs. 2.1 years, respectively), said Dr. Pisoni of the Medical University of South Carolina, Charleston.

Patients in the high- and low-risk groups also had similar baseline gender, body mass index, use of renin-angiotensin-aldosterone system blockers, eGFR, and co-morbidities, he noted.

Data used for this study were from the University of Alabama at Birmingham Chronic Kidney Disease Database. Patients had completed the Berlin questionnaire to assess for sleep apnea during a 9-month study period.

Obstructive sleep apnea is common in patients with type 2 diabetes and is also associated with glomerular hyperfiltration and proteinuria in patients with normal renal function, which raised the question of whether it might be related to chronic kidney disease progression, Dr. Pisoni explained. He noted that the association between obstructive sleep apnea and diabetic nephropathy has not been fully investigated.

The study demonstrated that the “simple approach” of assessing obstructive sleep apnea risk identifies patients who are also at increased risk of CKD progression, he said, adding that the findings require replication in a prospective cohort.

Dr. Pisoni reported having no disclosures.

PHILADELPHIA – Patients with type 2 diabetes, chronic kidney disease, and a high risk of obstructive sleep apnea have more rapid loss of kidney function than do similar patients with a low risk of sleep apnea, findings from a retrospective cohort study suggest.

Of 56 patients with diabetic nephropathy who underwent screening for obstructive sleep apnea, 34 (61%) were at high risk. Compared with 22 patients with a low risk score, the high-risk patients had a significantly greater loss of estimated glomerular filtration rate over time (median loss of -3.4 vs. 1.5 ml/min/1.73 m² per year for the high- vs. low-risk patients, respectively), Dr. Roberto Pisoni reported in a poster at the annual meeting of the American Society of Nephrology.

This finding was despite comparable blood pressure for the high- and low-risk groups (systolic: 141.7 and 143.7 mm Hg; diastolic: 72.0 and 72.4 mm Hg, respectively), proteinuria upon admission to a chronic kidney disease clinic (urinary protein/creatinine ratio, 1.9 and 1.6 g/g, respectively), and time spent in clinic (1.9 vs. 2.1 years, respectively), said Dr. Pisoni of the Medical University of South Carolina, Charleston.

Patients in the high- and low-risk groups also had similar baseline gender, body mass index, use of renin-angiotensin-aldosterone system blockers, eGFR, and co-morbidities, he noted.

Data used for this study were from the University of Alabama at Birmingham Chronic Kidney Disease Database. Patients had completed the Berlin questionnaire to assess for sleep apnea during a 9-month study period.

Obstructive sleep apnea is common in patients with type 2 diabetes and is also associated with glomerular hyperfiltration and proteinuria in patients with normal renal function, which raised the question of whether it might be related to chronic kidney disease progression, Dr. Pisoni explained. He noted that the association between obstructive sleep apnea and diabetic nephropathy has not been fully investigated.

The study demonstrated that the “simple approach” of assessing obstructive sleep apnea risk identifies patients who are also at increased risk of CKD progression, he said, adding that the findings require replication in a prospective cohort.

Dr. Pisoni reported having no disclosures.

PHILADELPHIA – Renal biopsies are a useful tool for optimizing outcomes in pregnant patients with active lupus nephritis, according to Dr. Derek M. Fine.

Although caution is advisable, a general aversion to biopsying pregnant patients is unwarranted, Dr. Fine of Johns Hopkins University, Baltimore, said at the meeting, sponsored by the American Society of Nephrology.

An important question to ask yourself when deciding if a biopsy should be performed is whether without it you will really know what you are treating.

“For me, it’s very, very scary to take care of a lupus patient when I don’t know what’s going on,” said Dr. Fine, director of the Nephrology Fellowship Program at Johns Hopkins.

Other important questions include whether findings on biopsy will change your management, and whether prior histopathology can help you identify the current problem.

“I would say if it was in the previous few months, yes it’s going to be useful. But once you’re 6 months or a year out, you don’t know what’s going on,” he said, noting that while an educated guess can be made that something similar is going on, one can’t rely on prior histopathology in such cases.

“I’m not saying do it with reckless abandon, but think about doing a biopsy,” he said.

An important benefit of performing a biopsy is disease classification to guide management. Another is differential diagnosis, he said, noting that between 20% and 50% of lupus patients have antiphospholipid antibodies, and that a biopsy can also detect thrombi in the kidney, differentiate preeclampsia if there’s a question about that, and identify focal segmental glomerulosclerosis, which is not an uncommon diagnosis on biopsy in African American patients.

As for the risks of biopsying a pregnant patient, the data are sparse – the largest available study was conducted 27 years ago – but they suggest that complication rates with biopsy during pregnancy are low, and that fetal loss is extremely unusual.

Concerns about preterm labor are often cited as a reason to avoid biopsy, but kidney biopsies are not particularly stress inducing. Bleeding is a concern, but bleeding risk has declined over time, and the procedure has become safer with the use of real-time ultrasound and smaller-gauge needles.

“Doppler technology can tell me there is a bleed, often right away, and interventional radiology availability, compared with 1987, is significant. It was really in its infancy back then, but now to get an angiogram is pretty easy and I can get it done within an hour of doing a kidney biopsy,” he said.

Furthermore, pregnant patients tend to have improved coagulation, and thus reduced bleeding risk, although increased renal blood flow may counteract some of that benefit.

In one study, he and his colleagues found that the risk of bleeding was not much different in lupus and nonlupus patients, at about 2.7%, and the risk was reduced by 50% among those with platelet counts greater than 100,000/mm³, he said.

However, the complication rate seen in patients who undergo biopsy is not insignificant, and these patients should be monitored extremely closely after the procedure.

“It’s a low risk, but a real one,” he said.

The literature documents biopsies performed at up to 32 weeks’ gestation, but biopsy may not be worthwhile later in pregnancy when empiric therapy is more reasonable because of a shorter course, and because the fetus is more viable, he said.

Also, if a bleeding event requiring an angiogram occurs, it is easiest to shield the fetus with lead up to about 24 weeks’ gestation. After that point, it can be more difficult to shield the fetus because of positioning, and this should be taken into consideration.

“I get a little bit nervous doing a kidney biopsy beyond 24 weeks, mainly for this reason,” he said.

If necessary, however, a biopsy can be performed up to 28 weeks’ gestation, he added.

Keep in mind that histopathology cannot be predicted based on clinical features alone. “We really need to get tissue to know what we’re treating,” he said, describing patients with similar clinical features, but different histopathology as an example of why biopsy is important.

A one-size-fits-all approach to treatment doesn’t work under these circumstances; biopsy can help spare patients unnecessary or dangerous treatments, and can help optimize treatment to improve outcomes, he said.

He recommended doing a biopsy for proteinuria of 500 mg/dL or more, avoiding biopsy beyond 28 weeks’ gestation, minimizing bleeding risk, and – from a medicolegal standpoint – ensuring fetal well-being before biopsy to ensure that the biopsy is not blamed for fetal death.

If a biopsy is not possible, make an educated guess as to what you think is going on, and treat accordingly, he said.

“The consensus is that active disease is bad for both fetal and maternal outcomes, and that pregnancy makes lupus worse,” he said, noting that studies have shown that only about 10% of women with active disease achieve a term pregnancy, more than half have a preterm birth, and more than a third experience fetal loss.

Ideally, disease activity would be optimized prior to pregnancy in a patient with lupus, as outcomes are vastly improved by a quiescent disease state, but when this is not successful or possible and a patient presents with pregnancy and active disease, a biopsy should be considered, he said.

Dr. Fine said he had no relevant financial disclosures.

PHILADELPHIA – Renal biopsies are a useful tool for optimizing outcomes in pregnant patients with active lupus nephritis, according to Dr. Derek M. Fine.

Although caution is advisable, a general aversion to biopsying pregnant patients is unwarranted, Dr. Fine of Johns Hopkins University, Baltimore, said at the meeting, sponsored by the American Society of Nephrology.

An important question to ask yourself when deciding if a biopsy should be performed is whether without it you will really know what you are treating.

“For me, it’s very, very scary to take care of a lupus patient when I don’t know what’s going on,” said Dr. Fine, director of the Nephrology Fellowship Program at Johns Hopkins.

Other important questions include whether findings on biopsy will change your management, and whether prior histopathology can help you identify the current problem.

“I would say if it was in the previous few months, yes it’s going to be useful. But once you’re 6 months or a year out, you don’t know what’s going on,” he said, noting that while an educated guess can be made that something similar is going on, one can’t rely on prior histopathology in such cases.

“I’m not saying do it with reckless abandon, but think about doing a biopsy,” he said.

An important benefit of performing a biopsy is disease classification to guide management. Another is differential diagnosis, he said, noting that between 20% and 50% of lupus patients have antiphospholipid antibodies, and that a biopsy can also detect thrombi in the kidney, differentiate preeclampsia if there’s a question about that, and identify focal segmental glomerulosclerosis, which is not an uncommon diagnosis on biopsy in African American patients.

As for the risks of biopsying a pregnant patient, the data are sparse – the largest available study was conducted 27 years ago – but they suggest that complication rates with biopsy during pregnancy are low, and that fetal loss is extremely unusual.

Concerns about preterm labor are often cited as a reason to avoid biopsy, but kidney biopsies are not particularly stress inducing. Bleeding is a concern, but bleeding risk has declined over time, and the procedure has become safer with the use of real-time ultrasound and smaller-gauge needles.

“Doppler technology can tell me there is a bleed, often right away, and interventional radiology availability, compared with 1987, is significant. It was really in its infancy back then, but now to get an angiogram is pretty easy and I can get it done within an hour of doing a kidney biopsy,” he said.

Furthermore, pregnant patients tend to have improved coagulation, and thus reduced bleeding risk, although increased renal blood flow may counteract some of that benefit.

In one study, he and his colleagues found that the risk of bleeding was not much different in lupus and nonlupus patients, at about 2.7%, and the risk was reduced by 50% among those with platelet counts greater than 100,000/mm³, he said.

However, the complication rate seen in patients who undergo biopsy is not insignificant, and these patients should be monitored extremely closely after the procedure.

“It’s a low risk, but a real one,” he said.

The literature documents biopsies performed at up to 32 weeks’ gestation, but biopsy may not be worthwhile later in pregnancy when empiric therapy is more reasonable because of a shorter course, and because the fetus is more viable, he said.

Also, if a bleeding event requiring an angiogram occurs, it is easiest to shield the fetus with lead up to about 24 weeks’ gestation. After that point, it can be more difficult to shield the fetus because of positioning, and this should be taken into consideration.

“I get a little bit nervous doing a kidney biopsy beyond 24 weeks, mainly for this reason,” he said.

If necessary, however, a biopsy can be performed up to 28 weeks’ gestation, he added.

Keep in mind that histopathology cannot be predicted based on clinical features alone. “We really need to get tissue to know what we’re treating,” he said, describing patients with similar clinical features, but different histopathology as an example of why biopsy is important.

A one-size-fits-all approach to treatment doesn’t work under these circumstances; biopsy can help spare patients unnecessary or dangerous treatments, and can help optimize treatment to improve outcomes, he said.

He recommended doing a biopsy for proteinuria of 500 mg/dL or more, avoiding biopsy beyond 28 weeks’ gestation, minimizing bleeding risk, and – from a medicolegal standpoint – ensuring fetal well-being before biopsy to ensure that the biopsy is not blamed for fetal death.

If a biopsy is not possible, make an educated guess as to what you think is going on, and treat accordingly, he said.

“The consensus is that active disease is bad for both fetal and maternal outcomes, and that pregnancy makes lupus worse,” he said, noting that studies have shown that only about 10% of women with active disease achieve a term pregnancy, more than half have a preterm birth, and more than a third experience fetal loss.

Ideally, disease activity would be optimized prior to pregnancy in a patient with lupus, as outcomes are vastly improved by a quiescent disease state, but when this is not successful or possible and a patient presents with pregnancy and active disease, a biopsy should be considered, he said.

Dr. Fine said he had no relevant financial disclosures.

PHILADELPHIA – Renal biopsies are a useful tool for optimizing outcomes in pregnant patients with active lupus nephritis, according to Dr. Derek M. Fine.

Although caution is advisable, a general aversion to biopsying pregnant patients is unwarranted, Dr. Fine of Johns Hopkins University, Baltimore, said at the meeting, sponsored by the American Society of Nephrology.

An important question to ask yourself when deciding if a biopsy should be performed is whether without it you will really know what you are treating.

“For me, it’s very, very scary to take care of a lupus patient when I don’t know what’s going on,” said Dr. Fine, director of the Nephrology Fellowship Program at Johns Hopkins.

Other important questions include whether findings on biopsy will change your management, and whether prior histopathology can help you identify the current problem.

“I would say if it was in the previous few months, yes it’s going to be useful. But once you’re 6 months or a year out, you don’t know what’s going on,” he said, noting that while an educated guess can be made that something similar is going on, one can’t rely on prior histopathology in such cases.

“I’m not saying do it with reckless abandon, but think about doing a biopsy,” he said.

An important benefit of performing a biopsy is disease classification to guide management. Another is differential diagnosis, he said, noting that between 20% and 50% of lupus patients have antiphospholipid antibodies, and that a biopsy can also detect thrombi in the kidney, differentiate preeclampsia if there’s a question about that, and identify focal segmental glomerulosclerosis, which is not an uncommon diagnosis on biopsy in African American patients.

As for the risks of biopsying a pregnant patient, the data are sparse – the largest available study was conducted 27 years ago – but they suggest that complication rates with biopsy during pregnancy are low, and that fetal loss is extremely unusual.

Concerns about preterm labor are often cited as a reason to avoid biopsy, but kidney biopsies are not particularly stress inducing. Bleeding is a concern, but bleeding risk has declined over time, and the procedure has become safer with the use of real-time ultrasound and smaller-gauge needles.

“Doppler technology can tell me there is a bleed, often right away, and interventional radiology availability, compared with 1987, is significant. It was really in its infancy back then, but now to get an angiogram is pretty easy and I can get it done within an hour of doing a kidney biopsy,” he said.

Furthermore, pregnant patients tend to have improved coagulation, and thus reduced bleeding risk, although increased renal blood flow may counteract some of that benefit.

In one study, he and his colleagues found that the risk of bleeding was not much different in lupus and nonlupus patients, at about 2.7%, and the risk was reduced by 50% among those with platelet counts greater than 100,000/mm³, he said.

However, the complication rate seen in patients who undergo biopsy is not insignificant, and these patients should be monitored extremely closely after the procedure.

“It’s a low risk, but a real one,” he said.

The literature documents biopsies performed at up to 32 weeks’ gestation, but biopsy may not be worthwhile later in pregnancy when empiric therapy is more reasonable because of a shorter course, and because the fetus is more viable, he said.

Also, if a bleeding event requiring an angiogram occurs, it is easiest to shield the fetus with lead up to about 24 weeks’ gestation. After that point, it can be more difficult to shield the fetus because of positioning, and this should be taken into consideration.

“I get a little bit nervous doing a kidney biopsy beyond 24 weeks, mainly for this reason,” he said.

If necessary, however, a biopsy can be performed up to 28 weeks’ gestation, he added.

Keep in mind that histopathology cannot be predicted based on clinical features alone. “We really need to get tissue to know what we’re treating,” he said, describing patients with similar clinical features, but different histopathology as an example of why biopsy is important.

A one-size-fits-all approach to treatment doesn’t work under these circumstances; biopsy can help spare patients unnecessary or dangerous treatments, and can help optimize treatment to improve outcomes, he said.

He recommended doing a biopsy for proteinuria of 500 mg/dL or more, avoiding biopsy beyond 28 weeks’ gestation, minimizing bleeding risk, and – from a medicolegal standpoint – ensuring fetal well-being before biopsy to ensure that the biopsy is not blamed for fetal death.

If a biopsy is not possible, make an educated guess as to what you think is going on, and treat accordingly, he said.

“The consensus is that active disease is bad for both fetal and maternal outcomes, and that pregnancy makes lupus worse,” he said, noting that studies have shown that only about 10% of women with active disease achieve a term pregnancy, more than half have a preterm birth, and more than a third experience fetal loss.

Ideally, disease activity would be optimized prior to pregnancy in a patient with lupus, as outcomes are vastly improved by a quiescent disease state, but when this is not successful or possible and a patient presents with pregnancy and active disease, a biopsy should be considered, he said.

Dr. Fine said he had no relevant financial disclosures.

PHILADELPHIA – Once-daily add-on liraglutide reduces HbA_1c in patients with type 2 diabetes and moderate renal impairment when compared with placebo, according to findings from the phase III LIRA-RENAL trial.

The effects on blood glucose occurred across glomerular filtration rate (GFR) subgroups, and no worsening of kidney function occurred during the randomized, double-blind, 26-week study, Dr. David Scott reported at Kidney Week 2014.

In 277 patients with stage 3 chronic kidney disease (CKD) who were randomized to receive either an oral daily dose of 1.8 mg of liraglutide or placebo in addition to existing oral antidiabetic agents and/or insulin therapy, active treatment was associated with a significantly greater overall reduction in mean HbA_1c from baseline to week 26 (–1.05% vs. –0.38%; estimated treatment difference, –0.66%). Similar reductions were seen in those with stage 3a disease (–1.10% vs. –0.35%; estimated treatment difference, –0.72%), and stage 3b disease (–0.97% vs. –0.40%; estimated treatment difference, –0.57%), Dr. Scott of Clinical Research Development Associates, Springfield Gardens, N.Y., reported at the meeting, which was sponsored by the American Society of Nephrology.

No significant treatment effect was observed on urinary albumin/creatinine ratio in any of the albuminuria subgroups. The estimated treatment ratios (liraglutide/placebo) were 1.09, 0.73, and 0.66 in those with normal (less than 30 mg/g), moderately increased (30-300 mg/g) or severely increased (greater than 300 mg/g) albuminuria levels.

Also, no difference was seen in estimated GFR change from baseline between the liraglutide and placebo groups (–1% vs. +1%, respectively), Dr. Scott said.

Adverse events and serious adverse events occurred in similar numbers of patients in the treatment and placebo groups (76% and 69%, and 10% and 11% of liraglutide and placebo patients, respectively), although those in the treatment group experienced more nausea and vomiting than did those in the placebo group (35.7% vs. 17.5%), he noted.

Confirmed hypoglycemia occurred in 11% and 17% of the liraglutide and placebo patients, respectively, but no real difference was seen between the groups with respect to severe hypoglycemia, he said.

Subjects were adults with body mass index of 20-45 kg/m² and HbA_1c of 7.0%-10.0%. All were on stable diabetes medication and had moderate renal impairment (estimated GFR of 30-59 mL/min/1.73 m²; modification of diet in renal disease).

“I think this is a very important study. It’s important, because as a clinical nephrologist, I’m faced day-to-day with the challenges of how to treat my diabetic patients with CKD. There are therapies that are contraindicated, there are therapies that are not well tolerated,” Dr. Scott said, explaining that treatment options remain limited for patients with diabetes and impaired renal function.

Further, while the incidence of diabetic nephropathy and diabetes has been declining, diabetes remains one of the most prevalent causes of CKD, and the incidence in some populations, including the elderly – who are at greatest risk for complications from therapy – has increased.

Although prior studies demonstrated that liraglutide was safe and well tolerated in patients with mild renal insufficiency, guidelines continue to include specific language suggesting that it is not indicated in the setting of CKD, Dr. Scott said.

The current findings provide additional evidence of the safety and efficacy of liraglutide in patients with type 2 diabetes and moderate renal impairment, he concluded.

The LIRA-RENAL trial was funded by Novo Nordisk. Dr. Scott reported having no disclosures.

PHILADELPHIA – Once-daily add-on liraglutide reduces HbA_1c in patients with type 2 diabetes and moderate renal impairment when compared with placebo, according to findings from the phase III LIRA-RENAL trial.

The effects on blood glucose occurred across glomerular filtration rate (GFR) subgroups, and no worsening of kidney function occurred during the randomized, double-blind, 26-week study, Dr. David Scott reported at Kidney Week 2014.

In 277 patients with stage 3 chronic kidney disease (CKD) who were randomized to receive either an oral daily dose of 1.8 mg of liraglutide or placebo in addition to existing oral antidiabetic agents and/or insulin therapy, active treatment was associated with a significantly greater overall reduction in mean HbA_1c from baseline to week 26 (–1.05% vs. –0.38%; estimated treatment difference, –0.66%). Similar reductions were seen in those with stage 3a disease (–1.10% vs. –0.35%; estimated treatment difference, –0.72%), and stage 3b disease (–0.97% vs. –0.40%; estimated treatment difference, –0.57%), Dr. Scott of Clinical Research Development Associates, Springfield Gardens, N.Y., reported at the meeting, which was sponsored by the American Society of Nephrology.

No significant treatment effect was observed on urinary albumin/creatinine ratio in any of the albuminuria subgroups. The estimated treatment ratios (liraglutide/placebo) were 1.09, 0.73, and 0.66 in those with normal (less than 30 mg/g), moderately increased (30-300 mg/g) or severely increased (greater than 300 mg/g) albuminuria levels.

Also, no difference was seen in estimated GFR change from baseline between the liraglutide and placebo groups (–1% vs. +1%, respectively), Dr. Scott said.

Adverse events and serious adverse events occurred in similar numbers of patients in the treatment and placebo groups (76% and 69%, and 10% and 11% of liraglutide and placebo patients, respectively), although those in the treatment group experienced more nausea and vomiting than did those in the placebo group (35.7% vs. 17.5%), he noted.

Confirmed hypoglycemia occurred in 11% and 17% of the liraglutide and placebo patients, respectively, but no real difference was seen between the groups with respect to severe hypoglycemia, he said.

Subjects were adults with body mass index of 20-45 kg/m² and HbA_1c of 7.0%-10.0%. All were on stable diabetes medication and had moderate renal impairment (estimated GFR of 30-59 mL/min/1.73 m²; modification of diet in renal disease).

“I think this is a very important study. It’s important, because as a clinical nephrologist, I’m faced day-to-day with the challenges of how to treat my diabetic patients with CKD. There are therapies that are contraindicated, there are therapies that are not well tolerated,” Dr. Scott said, explaining that treatment options remain limited for patients with diabetes and impaired renal function.

Further, while the incidence of diabetic nephropathy and diabetes has been declining, diabetes remains one of the most prevalent causes of CKD, and the incidence in some populations, including the elderly – who are at greatest risk for complications from therapy – has increased.

Although prior studies demonstrated that liraglutide was safe and well tolerated in patients with mild renal insufficiency, guidelines continue to include specific language suggesting that it is not indicated in the setting of CKD, Dr. Scott said.

The current findings provide additional evidence of the safety and efficacy of liraglutide in patients with type 2 diabetes and moderate renal impairment, he concluded.

The LIRA-RENAL trial was funded by Novo Nordisk. Dr. Scott reported having no disclosures.

PHILADELPHIA – Once-daily add-on liraglutide reduces HbA_1c in patients with type 2 diabetes and moderate renal impairment when compared with placebo, according to findings from the phase III LIRA-RENAL trial.

The effects on blood glucose occurred across glomerular filtration rate (GFR) subgroups, and no worsening of kidney function occurred during the randomized, double-blind, 26-week study, Dr. David Scott reported at Kidney Week 2014.

In 277 patients with stage 3 chronic kidney disease (CKD) who were randomized to receive either an oral daily dose of 1.8 mg of liraglutide or placebo in addition to existing oral antidiabetic agents and/or insulin therapy, active treatment was associated with a significantly greater overall reduction in mean HbA_1c from baseline to week 26 (–1.05% vs. –0.38%; estimated treatment difference, –0.66%). Similar reductions were seen in those with stage 3a disease (–1.10% vs. –0.35%; estimated treatment difference, –0.72%), and stage 3b disease (–0.97% vs. –0.40%; estimated treatment difference, –0.57%), Dr. Scott of Clinical Research Development Associates, Springfield Gardens, N.Y., reported at the meeting, which was sponsored by the American Society of Nephrology.

No significant treatment effect was observed on urinary albumin/creatinine ratio in any of the albuminuria subgroups. The estimated treatment ratios (liraglutide/placebo) were 1.09, 0.73, and 0.66 in those with normal (less than 30 mg/g), moderately increased (30-300 mg/g) or severely increased (greater than 300 mg/g) albuminuria levels.

Also, no difference was seen in estimated GFR change from baseline between the liraglutide and placebo groups (–1% vs. +1%, respectively), Dr. Scott said.

Adverse events and serious adverse events occurred in similar numbers of patients in the treatment and placebo groups (76% and 69%, and 10% and 11% of liraglutide and placebo patients, respectively), although those in the treatment group experienced more nausea and vomiting than did those in the placebo group (35.7% vs. 17.5%), he noted.

Confirmed hypoglycemia occurred in 11% and 17% of the liraglutide and placebo patients, respectively, but no real difference was seen between the groups with respect to severe hypoglycemia, he said.

Subjects were adults with body mass index of 20-45 kg/m² and HbA_1c of 7.0%-10.0%. All were on stable diabetes medication and had moderate renal impairment (estimated GFR of 30-59 mL/min/1.73 m²; modification of diet in renal disease).

“I think this is a very important study. It’s important, because as a clinical nephrologist, I’m faced day-to-day with the challenges of how to treat my diabetic patients with CKD. There are therapies that are contraindicated, there are therapies that are not well tolerated,” Dr. Scott said, explaining that treatment options remain limited for patients with diabetes and impaired renal function.

Further, while the incidence of diabetic nephropathy and diabetes has been declining, diabetes remains one of the most prevalent causes of CKD, and the incidence in some populations, including the elderly – who are at greatest risk for complications from therapy – has increased.

Although prior studies demonstrated that liraglutide was safe and well tolerated in patients with mild renal insufficiency, guidelines continue to include specific language suggesting that it is not indicated in the setting of CKD, Dr. Scott said.

The current findings provide additional evidence of the safety and efficacy of liraglutide in patients with type 2 diabetes and moderate renal impairment, he concluded.

The LIRA-RENAL trial was funded by Novo Nordisk. Dr. Scott reported having no disclosures.

PHILADELPHIA – A covered nitinol stent graft effectively restored and maintained patency of hemodialysis access routes that had been impaired by in-stent restenosis.

The combination of a stent graft plus angioplasty was significantly more effective than angioplasty alone at keeping the access routes open, Dr. Alexander Yevzlin reported at Kidney Week 2014.

Maintaining healthy vascular access is key for effective dialysis; this is usually accomplished by bare metal stenting. However, in-stent restenosis is so common that patients may need angioplasty every 3-6 months to maintain access patency.

In comparison, coronary angioplasty is usually sustained for at least 5 years, said Dr. Yevzlin, director of interventional nephrology at the University of Wisconsin, Madison. “This places a very large extra burden of morbidity on patients, and a large burden of cost on society.”

The ongoing RESCUE study is examining the Fluency Plus cardiovascular stent graft for in-stent restenosis. Fluency is a nitinol stent covered with a plastic graft of expanded polytetrafluoroethylene. Dr. Yevzlin reported preliminary 6-month data.

The study has randomized 265 patients with in-stent restenosis of a dialysis access circuit to treatment with either balloon angioplasty alone, or angioplasty plus the stent graft. The primary endpoints are access circuit primary patency at 6 months and 30-day safety. Safety endpoints are any additional interventions including surgery, hospitalization, or prolongation of an existing hospitalization; or death. The secondary endpoint is postintervention lesion patency (defined as the interval after the index intervention until the next reintervention at the original treatment site or until the extremity is abandoned for permanent access).

There were no safety issues, Dr. Yevzlin said; by 30 days, 97% of patients in both groups were still free of any adverse event.

By 6 months, access circuit patency was significantly higher among those who received stent grafts than those who had angioplasties alone. Postintervention lesion patency was 65% in the stent graft group and 10% in the angioplasty group – a significant difference.

The stent graft performed well in both arteriovenous grafts and fistulas. In a subgroup of those with an arteriovenous graft, the postinterventional lesion patency rate was 58% in the stent graft group and 5% in the angioplasty group. In the fistula subgroup, the rates were 72% and 15%, respectively.

The meeting was sponsored by the American Society of Nephrology. Dr. Yevzlin disclosed financial relationships with Bard Peripheral Vascular, the manufacturer of the stent graft; Phraxis; CytoPherx; and Covidien.

msullivan@frontlinemedcom.com

PHILADELPHIA – A covered nitinol stent graft effectively restored and maintained patency of hemodialysis access routes that had been impaired by in-stent restenosis.

The combination of a stent graft plus angioplasty was significantly more effective than angioplasty alone at keeping the access routes open, Dr. Alexander Yevzlin reported at Kidney Week 2014.

Maintaining healthy vascular access is key for effective dialysis; this is usually accomplished by bare metal stenting. However, in-stent restenosis is so common that patients may need angioplasty every 3-6 months to maintain access patency.

In comparison, coronary angioplasty is usually sustained for at least 5 years, said Dr. Yevzlin, director of interventional nephrology at the University of Wisconsin, Madison. “This places a very large extra burden of morbidity on patients, and a large burden of cost on society.”

The ongoing RESCUE study is examining the Fluency Plus cardiovascular stent graft for in-stent restenosis. Fluency is a nitinol stent covered with a plastic graft of expanded polytetrafluoroethylene. Dr. Yevzlin reported preliminary 6-month data.

The study has randomized 265 patients with in-stent restenosis of a dialysis access circuit to treatment with either balloon angioplasty alone, or angioplasty plus the stent graft. The primary endpoints are access circuit primary patency at 6 months and 30-day safety. Safety endpoints are any additional interventions including surgery, hospitalization, or prolongation of an existing hospitalization; or death. The secondary endpoint is postintervention lesion patency (defined as the interval after the index intervention until the next reintervention at the original treatment site or until the extremity is abandoned for permanent access).

There were no safety issues, Dr. Yevzlin said; by 30 days, 97% of patients in both groups were still free of any adverse event.

By 6 months, access circuit patency was significantly higher among those who received stent grafts than those who had angioplasties alone. Postintervention lesion patency was 65% in the stent graft group and 10% in the angioplasty group – a significant difference.

The stent graft performed well in both arteriovenous grafts and fistulas. In a subgroup of those with an arteriovenous graft, the postinterventional lesion patency rate was 58% in the stent graft group and 5% in the angioplasty group. In the fistula subgroup, the rates were 72% and 15%, respectively.

The meeting was sponsored by the American Society of Nephrology. Dr. Yevzlin disclosed financial relationships with Bard Peripheral Vascular, the manufacturer of the stent graft; Phraxis; CytoPherx; and Covidien.

msullivan@frontlinemedcom.com

PHILADELPHIA – A covered nitinol stent graft effectively restored and maintained patency of hemodialysis access routes that had been impaired by in-stent restenosis.

The combination of a stent graft plus angioplasty was significantly more effective than angioplasty alone at keeping the access routes open, Dr. Alexander Yevzlin reported at Kidney Week 2014.

Maintaining healthy vascular access is key for effective dialysis; this is usually accomplished by bare metal stenting. However, in-stent restenosis is so common that patients may need angioplasty every 3-6 months to maintain access patency.

In comparison, coronary angioplasty is usually sustained for at least 5 years, said Dr. Yevzlin, director of interventional nephrology at the University of Wisconsin, Madison. “This places a very large extra burden of morbidity on patients, and a large burden of cost on society.”

The ongoing RESCUE study is examining the Fluency Plus cardiovascular stent graft for in-stent restenosis. Fluency is a nitinol stent covered with a plastic graft of expanded polytetrafluoroethylene. Dr. Yevzlin reported preliminary 6-month data.

The study has randomized 265 patients with in-stent restenosis of a dialysis access circuit to treatment with either balloon angioplasty alone, or angioplasty plus the stent graft. The primary endpoints are access circuit primary patency at 6 months and 30-day safety. Safety endpoints are any additional interventions including surgery, hospitalization, or prolongation of an existing hospitalization; or death. The secondary endpoint is postintervention lesion patency (defined as the interval after the index intervention until the next reintervention at the original treatment site or until the extremity is abandoned for permanent access).

There were no safety issues, Dr. Yevzlin said; by 30 days, 97% of patients in both groups were still free of any adverse event.

By 6 months, access circuit patency was significantly higher among those who received stent grafts than those who had angioplasties alone. Postintervention lesion patency was 65% in the stent graft group and 10% in the angioplasty group – a significant difference.

The stent graft performed well in both arteriovenous grafts and fistulas. In a subgroup of those with an arteriovenous graft, the postinterventional lesion patency rate was 58% in the stent graft group and 5% in the angioplasty group. In the fistula subgroup, the rates were 72% and 15%, respectively.

The meeting was sponsored by the American Society of Nephrology. Dr. Yevzlin disclosed financial relationships with Bard Peripheral Vascular, the manufacturer of the stent graft; Phraxis; CytoPherx; and Covidien.

msullivan@frontlinemedcom.com

PHILADELPHIA – Extended time on hemodialysis each week produced some modest improvement in lab values but didn’t result in any overall increases in quality of life for patients.

A dialysis regimen of at least 24 hours weekly failed to confer any significant benefits on blood pressure, weight, or 12-month cardiovascular outcomes, Dr. Meg Jardine said at Kidney Week 2014, which was sponsored by the American Society of Nephrology.

A follow-up period of 12 months, however, probably isn’t long enough to detect any potential cardiovascular benefits, noted Dr. Jardine of the George Institute of Global Health of Sydney.

The ACTIVE Dialysis Multinational Trial was conducted at 40 centers in Australia, China, New Zealand, and the U.K. It randomized 200 patients with end-stage renal disease to either standard dialysis (12-18 hours weekly) or the extended regimen (24-28 hours). Dialysis could be carried out at home or in a center. The primary endpoint was any change in health-related quality of life as measured on the EQ-5D, an internationally validated health quality of life measure, which was administered every 3 months. The EQ-5D score ranges from 0-1, with 0 being death and 1 being perfect health.

Secondary outcomes included overall survival, changes in biochemical and hematological markers, and safety including vascular access issues. A prespecified subanalysis examined changes in left ventricular mass index.

Patients were a mean of 52 years old. Most (70%) were male. At baseline, they received dialysis for a mean of 14 hours per week; 88% of dialysis was performed at a dialysis center. Access was via a native arteriovenous fistula in 84% of patients. The baseline EQ-5D score was 0.76 in the standard-dialysis group and 0.79 in the extended-dialysis group.

After 12 months, neither of the groups experienced any significant improvements in overall quality of life measures, Dr. Jardine said. There was a nonsignificant indication that the physical health subscale improved among patients who had the extended dialysis. There was no change in the mental health subscale in either group.

Patients in the extended-dialysis group did experience some significant improvements in laboratory measures. Potassium and phosphate levels declined significantly from baseline – enough to eliminate the need for a phosphate binder for many, she said. Calcium increased significantly, as did hemoglobin.

Both diastolic and systolic blood pressure improved somewhat, and although those improvements were not statistically significant, they did confer a significant decrease in the need for antihypertensive therapy.

At the 12-month follow up, imaging revealed that patients in the extended-dialysis group had a greater left ventricular mass – a mean of 2.84 g/m² more than that seen in the standard-dialysis group. The short follow-up time, however, makes interpretation of this finding difficult, Dr. Jardine said.

There were no significant differences in serious adverse effects between the groups. There were two deaths and three transplants in the standard arm, compared with five deaths and two transplants in the extended dialysis arm – not a significant difference.

Dr. Jardine disclosed that she has received honoraria from Servier Laboratories and Amgen.

msullivan@frontlinemedcom.com

PHILADELPHIA – Extended time on hemodialysis each week produced some modest improvement in lab values but didn’t result in any overall increases in quality of life for patients.

A dialysis regimen of at least 24 hours weekly failed to confer any significant benefits on blood pressure, weight, or 12-month cardiovascular outcomes, Dr. Meg Jardine said at Kidney Week 2014, which was sponsored by the American Society of Nephrology.

A follow-up period of 12 months, however, probably isn’t long enough to detect any potential cardiovascular benefits, noted Dr. Jardine of the George Institute of Global Health of Sydney.

The ACTIVE Dialysis Multinational Trial was conducted at 40 centers in Australia, China, New Zealand, and the U.K. It randomized 200 patients with end-stage renal disease to either standard dialysis (12-18 hours weekly) or the extended regimen (24-28 hours). Dialysis could be carried out at home or in a center. The primary endpoint was any change in health-related quality of life as measured on the EQ-5D, an internationally validated health quality of life measure, which was administered every 3 months. The EQ-5D score ranges from 0-1, with 0 being death and 1 being perfect health.

Secondary outcomes included overall survival, changes in biochemical and hematological markers, and safety including vascular access issues. A prespecified subanalysis examined changes in left ventricular mass index.

Patients were a mean of 52 years old. Most (70%) were male. At baseline, they received dialysis for a mean of 14 hours per week; 88% of dialysis was performed at a dialysis center. Access was via a native arteriovenous fistula in 84% of patients. The baseline EQ-5D score was 0.76 in the standard-dialysis group and 0.79 in the extended-dialysis group.

After 12 months, neither of the groups experienced any significant improvements in overall quality of life measures, Dr. Jardine said. There was a nonsignificant indication that the physical health subscale improved among patients who had the extended dialysis. There was no change in the mental health subscale in either group.

Patients in the extended-dialysis group did experience some significant improvements in laboratory measures. Potassium and phosphate levels declined significantly from baseline – enough to eliminate the need for a phosphate binder for many, she said. Calcium increased significantly, as did hemoglobin.

Both diastolic and systolic blood pressure improved somewhat, and although those improvements were not statistically significant, they did confer a significant decrease in the need for antihypertensive therapy.

At the 12-month follow up, imaging revealed that patients in the extended-dialysis group had a greater left ventricular mass – a mean of 2.84 g/m² more than that seen in the standard-dialysis group. The short follow-up time, however, makes interpretation of this finding difficult, Dr. Jardine said.

There were no significant differences in serious adverse effects between the groups. There were two deaths and three transplants in the standard arm, compared with five deaths and two transplants in the extended dialysis arm – not a significant difference.

Dr. Jardine disclosed that she has received honoraria from Servier Laboratories and Amgen.

msullivan@frontlinemedcom.com

PHILADELPHIA – Extended time on hemodialysis each week produced some modest improvement in lab values but didn’t result in any overall increases in quality of life for patients.

A dialysis regimen of at least 24 hours weekly failed to confer any significant benefits on blood pressure, weight, or 12-month cardiovascular outcomes, Dr. Meg Jardine said at Kidney Week 2014, which was sponsored by the American Society of Nephrology.

A follow-up period of 12 months, however, probably isn’t long enough to detect any potential cardiovascular benefits, noted Dr. Jardine of the George Institute of Global Health of Sydney.

The ACTIVE Dialysis Multinational Trial was conducted at 40 centers in Australia, China, New Zealand, and the U.K. It randomized 200 patients with end-stage renal disease to either standard dialysis (12-18 hours weekly) or the extended regimen (24-28 hours). Dialysis could be carried out at home or in a center. The primary endpoint was any change in health-related quality of life as measured on the EQ-5D, an internationally validated health quality of life measure, which was administered every 3 months. The EQ-5D score ranges from 0-1, with 0 being death and 1 being perfect health.

Secondary outcomes included overall survival, changes in biochemical and hematological markers, and safety including vascular access issues. A prespecified subanalysis examined changes in left ventricular mass index.

Patients were a mean of 52 years old. Most (70%) were male. At baseline, they received dialysis for a mean of 14 hours per week; 88% of dialysis was performed at a dialysis center. Access was via a native arteriovenous fistula in 84% of patients. The baseline EQ-5D score was 0.76 in the standard-dialysis group and 0.79 in the extended-dialysis group.

After 12 months, neither of the groups experienced any significant improvements in overall quality of life measures, Dr. Jardine said. There was a nonsignificant indication that the physical health subscale improved among patients who had the extended dialysis. There was no change in the mental health subscale in either group.

Patients in the extended-dialysis group did experience some significant improvements in laboratory measures. Potassium and phosphate levels declined significantly from baseline – enough to eliminate the need for a phosphate binder for many, she said. Calcium increased significantly, as did hemoglobin.

Both diastolic and systolic blood pressure improved somewhat, and although those improvements were not statistically significant, they did confer a significant decrease in the need for antihypertensive therapy.

At the 12-month follow up, imaging revealed that patients in the extended-dialysis group had a greater left ventricular mass – a mean of 2.84 g/m² more than that seen in the standard-dialysis group. The short follow-up time, however, makes interpretation of this finding difficult, Dr. Jardine said.

There were no significant differences in serious adverse effects between the groups. There were two deaths and three transplants in the standard arm, compared with five deaths and two transplants in the extended dialysis arm – not a significant difference.

Dr. Jardine disclosed that she has received honoraria from Servier Laboratories and Amgen.

msullivan@frontlinemedcom.com

PHILADELPHIA – ZS-9, an investigational cation exchanger designed to trap potassium in the gut, effectively and rapidly restores and maintains normokalemia in hyperkalemic patients with diabetes and significant renal impairment, according to a subgroup analysis of data from a randomized, placebo-controlled phase III trial.

Treatment with the first-in-class insoluble, nonabsorbed zirconium silicate, which was designed and engineered to have a three-dimensional crystalline lattice structure that preferentially traps potassium ions, was shown to have clinically and statistically significant benefit at daily oral doses of 5 mg and 10 mg, compared with placebo in the overall study population of 753 patients with hyperkalemia and underlying diabetes, heart failure, or chronic kidney disease.

The current analysis included 366 patients who had diabetes and an estimated glomerular filtration rate less than 60 mL/min/1.73m². The patients, who had baseline potassium levels of 5.0-6.5 mEq/L (mean of 5.3 mEq/L) were randomized to oral ZS-9 at doses of 1.25, 2.5, 5, or 10 g or placebo given three times daily for the first 48 hours. Following this acute phase, those with a potassium level of 3.5-5.0 mEq/L were rerandomized to either the same ZS-9 acute-phase dose once daily for days 3-15 or placebo.

In the subgroup, ZS-9 treatment was associated with a significant decrease in potassium at 48 hours (decreases of -0.45, -0.59, and -0.81 mEq/L in the 2.5-, 5-, and 10-g groups, respectively, compared with +0.24 mEq/L in the placebo group, Dr. Bhupinder Singh reported at the meeting sponsored by the American Society of Nephrology.

During the maintenance phase, patients receiving a 10-g dose of ZS-9 maintained normokalemia (4.5 mEq/L at day 3 vs. 4.6 mEq/L at day 15) vs. placebo (4.4 mEq/L at day 3, vs. 5.1 mEq/L at day 15). Similar results were seen in the 5-mg treatment group, Dr. Singh of Apex Research, Riverside, Calif. said.

“Hyperkalemia is a common and serious complication in patients with diabetes who have chronic kidney disease, particularly those who are treated with renin-angiotensin-aldosterone system (RAAS) inhibitors. Even mild to moderate hyperkalemia has been recently shown to be associated with increased mortality,” Dr. Singh said, noting that concerns about the seriousness of hyperkalemia have likely led to under-prescription of RAAS inhibitors, which have been proven to have cardio- and renoprotective action, but which are associated with hyperkalemia.

In head-to-head in vitro studies, ZS-9 has been shown to be more than 125 times more selective than sodium polystyrene sulfonate (SPS) – the current mainstay of treatment for hyperkalemia), and to have more than 9 times the potassium-binding capacity.

In the current analysis, ZS-9 was associated with a “fairly acute” effect, reducing potassium levels significantly within 1 hour, and to less than 5 mEq/L within 4 hours. The study also was published Nov. 21 in the New England Journal of Medicine (doi:10.1056/NEJMoa1411487).

In both the overall study population and the subgroup with diabetes and chronic kidney disease, ZS-9 discontinuation at the end of the study was associated with recurrence of hyperkalemia, indicating a need for continued use. The adverse event profile was similar in the treatment and placebo groups in both studies.

The findings suggest that long-term treatment with ZS-9 may allow continuation of chronic RAAS inhibition in patients with diabetes and chronic kidney disease, Dr. Sing said, adding that long-term treatment studies are underway.

This study was funded by ZS Pharma Inc., which is developing ZS-9. Dr. Singh is a consultant to ZS Pharma Inc.

PHILADELPHIA – ZS-9, an investigational cation exchanger designed to trap potassium in the gut, effectively and rapidly restores and maintains normokalemia in hyperkalemic patients with diabetes and significant renal impairment, according to a subgroup analysis of data from a randomized, placebo-controlled phase III trial.

Treatment with the first-in-class insoluble, nonabsorbed zirconium silicate, which was designed and engineered to have a three-dimensional crystalline lattice structure that preferentially traps potassium ions, was shown to have clinically and statistically significant benefit at daily oral doses of 5 mg and 10 mg, compared with placebo in the overall study population of 753 patients with hyperkalemia and underlying diabetes, heart failure, or chronic kidney disease.

The current analysis included 366 patients who had diabetes and an estimated glomerular filtration rate less than 60 mL/min/1.73m². The patients, who had baseline potassium levels of 5.0-6.5 mEq/L (mean of 5.3 mEq/L) were randomized to oral ZS-9 at doses of 1.25, 2.5, 5, or 10 g or placebo given three times daily for the first 48 hours. Following this acute phase, those with a potassium level of 3.5-5.0 mEq/L were rerandomized to either the same ZS-9 acute-phase dose once daily for days 3-15 or placebo.

In the subgroup, ZS-9 treatment was associated with a significant decrease in potassium at 48 hours (decreases of -0.45, -0.59, and -0.81 mEq/L in the 2.5-, 5-, and 10-g groups, respectively, compared with +0.24 mEq/L in the placebo group, Dr. Bhupinder Singh reported at the meeting sponsored by the American Society of Nephrology.

During the maintenance phase, patients receiving a 10-g dose of ZS-9 maintained normokalemia (4.5 mEq/L at day 3 vs. 4.6 mEq/L at day 15) vs. placebo (4.4 mEq/L at day 3, vs. 5.1 mEq/L at day 15). Similar results were seen in the 5-mg treatment group, Dr. Singh of Apex Research, Riverside, Calif. said.

“Hyperkalemia is a common and serious complication in patients with diabetes who have chronic kidney disease, particularly those who are treated with renin-angiotensin-aldosterone system (RAAS) inhibitors. Even mild to moderate hyperkalemia has been recently shown to be associated with increased mortality,” Dr. Singh said, noting that concerns about the seriousness of hyperkalemia have likely led to under-prescription of RAAS inhibitors, which have been proven to have cardio- and renoprotective action, but which are associated with hyperkalemia.

In head-to-head in vitro studies, ZS-9 has been shown to be more than 125 times more selective than sodium polystyrene sulfonate (SPS) – the current mainstay of treatment for hyperkalemia), and to have more than 9 times the potassium-binding capacity.

In the current analysis, ZS-9 was associated with a “fairly acute” effect, reducing potassium levels significantly within 1 hour, and to less than 5 mEq/L within 4 hours. The study also was published Nov. 21 in the New England Journal of Medicine (doi:10.1056/NEJMoa1411487).

In both the overall study population and the subgroup with diabetes and chronic kidney disease, ZS-9 discontinuation at the end of the study was associated with recurrence of hyperkalemia, indicating a need for continued use. The adverse event profile was similar in the treatment and placebo groups in both studies.

The findings suggest that long-term treatment with ZS-9 may allow continuation of chronic RAAS inhibition in patients with diabetes and chronic kidney disease, Dr. Sing said, adding that long-term treatment studies are underway.

This study was funded by ZS Pharma Inc., which is developing ZS-9. Dr. Singh is a consultant to ZS Pharma Inc.

PHILADELPHIA – ZS-9, an investigational cation exchanger designed to trap potassium in the gut, effectively and rapidly restores and maintains normokalemia in hyperkalemic patients with diabetes and significant renal impairment, according to a subgroup analysis of data from a randomized, placebo-controlled phase III trial.

Treatment with the first-in-class insoluble, nonabsorbed zirconium silicate, which was designed and engineered to have a three-dimensional crystalline lattice structure that preferentially traps potassium ions, was shown to have clinically and statistically significant benefit at daily oral doses of 5 mg and 10 mg, compared with placebo in the overall study population of 753 patients with hyperkalemia and underlying diabetes, heart failure, or chronic kidney disease.

The current analysis included 366 patients who had diabetes and an estimated glomerular filtration rate less than 60 mL/min/1.73m². The patients, who had baseline potassium levels of 5.0-6.5 mEq/L (mean of 5.3 mEq/L) were randomized to oral ZS-9 at doses of 1.25, 2.5, 5, or 10 g or placebo given three times daily for the first 48 hours. Following this acute phase, those with a potassium level of 3.5-5.0 mEq/L were rerandomized to either the same ZS-9 acute-phase dose once daily for days 3-15 or placebo.

In the subgroup, ZS-9 treatment was associated with a significant decrease in potassium at 48 hours (decreases of -0.45, -0.59, and -0.81 mEq/L in the 2.5-, 5-, and 10-g groups, respectively, compared with +0.24 mEq/L in the placebo group, Dr. Bhupinder Singh reported at the meeting sponsored by the American Society of Nephrology.

During the maintenance phase, patients receiving a 10-g dose of ZS-9 maintained normokalemia (4.5 mEq/L at day 3 vs. 4.6 mEq/L at day 15) vs. placebo (4.4 mEq/L at day 3, vs. 5.1 mEq/L at day 15). Similar results were seen in the 5-mg treatment group, Dr. Singh of Apex Research, Riverside, Calif. said.

“Hyperkalemia is a common and serious complication in patients with diabetes who have chronic kidney disease, particularly those who are treated with renin-angiotensin-aldosterone system (RAAS) inhibitors. Even mild to moderate hyperkalemia has been recently shown to be associated with increased mortality,” Dr. Singh said, noting that concerns about the seriousness of hyperkalemia have likely led to under-prescription of RAAS inhibitors, which have been proven to have cardio- and renoprotective action, but which are associated with hyperkalemia.

In head-to-head in vitro studies, ZS-9 has been shown to be more than 125 times more selective than sodium polystyrene sulfonate (SPS) – the current mainstay of treatment for hyperkalemia), and to have more than 9 times the potassium-binding capacity.

In the current analysis, ZS-9 was associated with a “fairly acute” effect, reducing potassium levels significantly within 1 hour, and to less than 5 mEq/L within 4 hours. The study also was published Nov. 21 in the New England Journal of Medicine (doi:10.1056/NEJMoa1411487).

In both the overall study population and the subgroup with diabetes and chronic kidney disease, ZS-9 discontinuation at the end of the study was associated with recurrence of hyperkalemia, indicating a need for continued use. The adverse event profile was similar in the treatment and placebo groups in both studies.

The findings suggest that long-term treatment with ZS-9 may allow continuation of chronic RAAS inhibition in patients with diabetes and chronic kidney disease, Dr. Sing said, adding that long-term treatment studies are underway.

This study was funded by ZS Pharma Inc., which is developing ZS-9. Dr. Singh is a consultant to ZS Pharma Inc.