Active vitamin D treatment for reduction of residual proteinuria: a systematic review

Abstract

Despite renin-angiotensin-aldosterone system blockade, which retards progression of CKD by reducing proteinuria, many patients with CKD have residual proteinuria, an independent risk factor for disease progression. We aimed to address whether active vitamin D analogs reduce residual proteinuria. We systematically searched for trials published between 1950 and September of 2012 in the Medline, Embase, and Cochrane Library databases. All randomized controlled trials of vitamin D analogs in patients with CKD that reported an effect on proteinuria with sample size≥50 were selected. Mean differences of proteinuria change over time and odds ratios for reaching ≥15% proteinuria decrease from baseline to last measurement were synthesized under a random effects model. From 907 citations retrieved, six studies (four studies with paricalcitol and two studies with calcitriol) providing data for 688 patients were included in the meta-analysis. Most patients (84%) used an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker throughout the study. Active vitamin D analogs reduced proteinuria (weighted mean difference from baseline to last measurement was -16% [95% CI, -13% to -18%]) compared with controls (+6% [95% CI, 0% to +12%]; P<0.001). Proteinuria reduction was achieved more commonly in patients treated with an active vitamin D analog (204/390 patients) than control patients (86/298 patients; OR, 2.72 [95% CI, 1.82 to 4.07]; P<0.001). Thus, active vitamin D analogs may further reduce proteinuria in CKD patients in addition to current regimens. Future studies should address whether vitamin D therapy also retards progressive renal functional decline.

Figure 1.

Flowchart of the process to identify eligible studies.

Figure 2.

Effect of active vitamin D or control treatment on proteinuria in the meta-analysis. (Upper panel) Relative proteinuria change from baseline to last available measurement for all studies with available data. P value (overall effect) is for the comparison between the proteinuria change during active vitamin D treatment and the proteinuria change during control treatment. (Lower panel) Odds ratio of a relevant proteinuria reduction for active vitamin D analog versus control treatment. A relevant reduction of proteinuria was defined as a reduction of ≥15% in proteinuria or albuminuria in most studies. UAE, urinary albumin excretion; UP, proteinuria.

Figure 3.

Subgroup analyses for the effects of vitamin D analogs on proteinuria reduction.