Efficacy and safety of vitamin D supplementation in diabetic kidney disease: an umbrella review of systematic reviews and meta-analyses

Why clinicians should know about it

• Picked for Nephrology (paper of the day, 31 July 2026).

Abstract

BACKGROUND: Diabetic kidney disease (DKD), including classical diabetic nephropathy, is a leading cause of chronic kidney disease and kidney replacement therapy. Vitamin D supplementation has been proposed to reduce albuminuria, but the available reviews are heterogeneous and redundant. OBJECTIVE: To critically evaluate and summarize the efficacy and safety of native vitamin D and active vitamin D analogs in adults with DKD, including studies reported as diabetic nephropathy (DN). METHODS: An overview of reviews registered in PROSPERO (CRD420251250914). Systematic reviews, with or without meta-analysis, were searched in MEDLINE/PubMed, Embase, the Cochrane Library, Web of Science, and Scopus, without language restrictions, through April 2, 2026. Methodological quality was assessed with AMSTAR-2, risk of bias with ROBIS, overlap with Corrected Covered Area (CCA), and certainty of evidence with GRADE. The synthesis used one anchor review per outcome, without de novo quantitative reanalysis. RESULTS: Eleven reviews met the eligibility criteria; nine provided evidence derived from randomized trials or separable randomized-trial data, and two were retained as contextual evidence. GRADE certainty was low for the surrogate urinary outcomes UACR and UAER, low to very low for 24-hour proteinuria, and very low or not evaluable for renal function, kidney replacement therapy, mortality, cardiovascular events, safety, and metabolic-inflammatory outcomes. Overlap was high (overall CCA, 13.5%; RCT-derived corpus, 14.1%). The evidence was compatible with low-certainty reductions in surrogate urinary outcomes, especially UACR and UAER, without consistent benefit for eGFR, serum creatinine, kidney replacement therapy, mortality, or cardiovascular events; safety was insufficiently reported. CONCLUSIONS: Vitamin D shows a low-certainty reduction in surrogate urinary markers of albuminuria/proteinuria in DKD, but current evidence is insufficient to support vitamin D as a specific renoprotective intervention beyond conventional indications for deficiency or mineral and bone disorders. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251250914, identifier CRD420251250914.

Abstract as published, via PubMed.