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Paricalcitol Added to Hypertension Therapy Lowers Albuminuria in Patients With Diabetes and Chronic Kidney Disease: Presented at Renal Week 2009

By Kristina Rebelo

SAN DIEGO -- November 3, 2009 -- Paricalcitol 2 mcg/day added to an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker therapy lowers albuminuria in patients with diabetes and chronic kidney disease, according to trial results released here at the American Society of Nephrology (ASN) Renal Week 2009.

The high risk for progressive renal failure in diabetics correlates with residual albuminuria. Paricalcitol has albuminuria-lowering effects, as found in preclinical and pilot clinical observations.

Paricalcitol -- a synthetically manufactured analogue of calcitriol, the metabolically active form of vitamin D -- appears to offer a novel approach to lowering renal risk, noted lead author Dick de Zeeuw, MD, PhD, University Medical Center Groningen, Groningen, the Netherlands. Dr. de Zeeuw presented the results of the study here at a late-breaking clinical trials session on October 30.

The selective Vitamin D Receptor Activation (VDRA) for Albuminuria Lowering (VITAL) study was a double-masked, controlled clinical trial of 281 patients with type 2 diabetes. Subjects' urinary albumin-to-creatinine ratio (UACR) was 100 to 3,000 mg/g, estimated glomerular filtration rate was 15 to 90 mL/min/1.73 m², corrected serum calcium level was less than 9.8 mg/dL, and intact parathyroid hormone levels were 35 to 500 pg/mL.

For 24 weeks, patients were randomised in a 1:1:1 ratio to receive placebo or paricalcitol 1 or 2 mcg/day. The study's primary efficacy analysis was the comparison of percentage changes from baseline to the last on-treatment UACR for the combined-dose group versus the placebo group in the intention-to-treat population.

There was a 15% greater decrease in UACR observed in the combined paricalcitol group compared with the change in the placebo group (P = .053). A dose-response relationship, the study said, was shown, with an 11% greater change for the 1-mcg dose (P = .229) and 18% greater change for the 2-mcg dose (P = .053) versus the placebo group.

The analyses of responders (those who achieved 15% or greater UACR reduction from baseline) demonstrated a difference between placebo and the 1-mcg dose (40% vs 52%, respectively, P = .102); placebo and the 2-mcg dose (40% vs 55%, respectively, P = .038); and placebo versus combined dose (40% versus 54%, respectively, P = .038).

There was a UACR decrease documented for the 2-mcg group (P = .014) with repeated measures analyses of all time points. There was an increase toward baseline UACR recorded at 30 and 60 days after subjects stopped paricalcitol.

"Blood pressure levels showed no significant difference between groups, and there were no increases in clinical or biochemical adverse events compared with the placebo group," noted Dr. de Zeeuw.

Funding for this study was provided by Abbott Laboratories.

[Presentation title: Selective Vitamin D Receptor Activation (VDRA) for Albuminuria Lowering (VITAL) Study in Type 2 Diabetic Nephropathy. Abstract LB-002]

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