VITAMIN D SUPPLEMENTATION AND ITS EFFECTS ON PROTEINURIA REDUCTION IN CKD: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract

Background:

Proteinuria is a key symptom of chronic kidney disease (CKD) development, and it is linked to unfavorable outcomes in renal status. Residual proteinuria can be a common occurrence regardless of optimization of standard therapy. However, vitamin D and analogs have been suggested as adjunctive therapy given their possible anti-inflammatory and renin-angiotensin system-regulating effects, and trial results are incongruent.

Objectives:

To assess whether vitamin D supplementation is associated with a reduction in proteinuria or albuminuria in patients with CKD based on a systematic review and meta-analysis of randomized controlled trials.

Methods:

This systematic review and meta-analysis was carried out in accordance with criteria of PRISMA 2020. Randomized controlled trials evaluating nutritional or active vitamin D supplementation among adult CKD populations and reporting outcomes of proteinuria/albuminuria were included. Seven RCTs were pooled using random-effect model (DerSimonian & Laird) with standardized mean difference (Hedges g) as a summary measure. In the case where the results were in the form of median (IQR), results were transformed to mean (SD) through known means. Two more interventional studies with no extractable between groups data were combined in a narrative fashion as supportive evidence. Risk of bias was evaluated using the RoB 2.

Results:

It included 9 studies, 7 of them RCTs in the quantitative synthesis, and 2 supportive interventional studies in the narrative synthesis. The number of participants in the meta-analysis was 379. Vitamin D supplementation had a significant beneficial treatment effect on proteinuria/albuminuria compared with control (SMD [Hedges g] = -0.372, 95% CI -0.635 to -0.110, P = 0.005), using random-effects model. The heterogeneity was moderate (I² 38.9 percent). The two supportive interventional studies showed tendencies of decreased albumin excretion following the vitamin D treatment but could not provide poolable between groups data.

Conclusion:

Across seven randomized trials, vitamin D supplementation was linked with a significant decrease in proteinuria/albuminuria in CKD, moderate heterogeneity. These results indicate that vitamin D may be used as an adjunct treatment to reduce proteinuria, but more large-scale measures with standardized results and longer follow-up are necessary to establish the best regimens and responsive subgroups.