Additive renoprotective effects of oral calcitriol on patients with IgA nephropathy receiving RAS blockers

Abstract

Background Patients with immunoglobulin A nephropathy (IgAN) and moderate proteinuria are at risk of progressive renal failure despite the maximal use of renin-angiotensin system blockers (RASBs). This study evaluated the efficacy of active vitamin D in reducing proteinuria in patients with IgAN receiving RASBs.Methods In this double-blind, placebo-controlled trial, we enrolled biopsy-confirmed patients with IgAN and persistent proteinuria (0.5-3.5 g/day) after maximal use of RASBs. Patients were randomized to receive either 0.25 mu g/day of calcitriol or placebo for 12 months. The primary outcomes were the change in the mean urinary protein:creatinine ratio (UPCR) and daily urinary protein excretion during the treatment.Results A total of 138 patients from six medical centres were enrolled and assigned to receive a placebo (n = 69) or 0.25 mu g of calcitriol (n = 69) and 115 patients (83.3%) completed the study. The calcitriol group showed a greater reduction in geometric means of UPCR {mean difference -187 mg/g [95% confidence interval (CI) -370.6 to -4.0], P = .04} and urinary albumin:creatinine ratio [-162 mg/g (95% CI -290.9 to -34.6), P = .01] than placebo. Changes in daily urinary protein excretion were -3.5% (from 1.32 to 1.02 g/day) in the control group and -13.1% (from 1.29 to 0.97 g/day) in the calcitriol group, without any statistically significant differences (P = .11). The annual decrease of the estimated glomerular filtration rate (eGFR) was -0.32 ml/min/1.73 m2 (95% CI -2.54 to 1.99) in the calcitriol group and -3.64 ml/min/1.73 m2 (95% CI -5.70 to -1.58) in the placebo group (calcitriol versus placebo over time, P = .02). Adverse events were comparable between the groups.Conclusion The addition of 0.25 mu g/day calcitriol to RASBs safely lowered residual proteinuria and slowed the eGFR decline in patients with IgAN, suggesting a potential therapeutic role for calcitriol in this population.