Journal Scan Summary Title: Selective Vitamin D Receptor Activation With Paricalcitol for Reduction of Albuminuria in Patients With Type 2 Diabetes (VITAL Study): A Randomized Controlled Trial
Date Posted: November 3, 2010
Authors: de Zeeuw D, Agarwal R, Amdahl M, et al.
Citation: Lancet 2010;Nov 3:[Epub ahead of print].
Study Question:
What is the effect of paricalcitol on albuminuria in patients with diabetic nephropathy?
Methods:
In this multinational, placebo-controlled, double-blind trial, the investigators enrolled patients with type 2 diabetes and albuminuria who were receiving angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs). Patients were assigned (1:1:1) by computer-generated randomization sequence to receive 24 weeks’ treatment with placebo, 1 µg/day paricalcitol, or 2 µg/day paricalcitol. The primary endpoint was the percentage change in geometric mean urinary albumin-to-creatinine ratio (UACR) from baseline to last measurement during treatment for the combined paricalcitol groups versus the placebo group. Analysis was by intention to treat.
Results:
Between February 2007 and October 2008, 281 patients were enrolled and assigned to receive placebo (n = 93), 1 µg paricalcitol (n = 93), or 2 µg paricalcitol (n = 95); 88 patients on placebo, 92 on 1 µg paricalcitol, and 92 on 2 µg paricalcitol received at least one dose of study drug, and had UACR data at baseline and at least one time point during treatment, and thus were included in the primary analysis. Change in UACR was: –3% (from 61 to 60 mg/mmol; 95% confidence interval [CI], –16 to 13) in the placebo group; –16% (from 62 to 51 mg/mmol; –24 to –9) in the combined paricalcitol groups, with a between-group difference versus placebo of –15% (95% CI –28 to 1; p = 0.071); –14% (from 63 to 54 mg/mmol; –24 to –1) in the 1 µg paricalcitol group, with a between-group difference versus placebo of –11% (95% CI –27 to 8; p = 0.23); and –20% (from 61 to 49 mg/mmol; –30 to –8) in the 2 µg paricalcitol group, with a between-group difference versus placebo of –18% (95% CI, –32 to 0; p = 0.053). Patients on 2 µg paricalcitol showed an early, sustained reduction in UACR, ranging from –18% to –28% (p = 0.014 vs. placebo). Incidence of hypercalcemia, adverse events, and serious adverse events was similar between groups receiving paricalcitol versus placebo.
Conclusions:
The authors concluded that the addition of 2 µg/day paricalcitol to renin–angiotensin–aldosterone system (RAAS) inhibition safely lowers residual albuminuria in patients with diabetic nephropathy.
Perspective:
The study demonstrates that 24 weeks’ treatment with 2 µg paricalcitol daily reduced residual albuminuria in patients with type 2 diabetic nephropathy who were on stable doses of ACE inhibitors or ARBs, particularly in those with high dietary sodium intake. Given that existing drug strategies have substantial limitations and have not been very successful in preventing kidney failure, paricalcitol could be an important adjunctive treatment, providing optimum management of renal osteodystrophy, with little hypercalcemia, and lowering residual albuminuria. Additional studies of paricalcitol with hard renal outcomes are indicated to definitively prove its renal and cardiovascular protective effects.
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