Are There Any Pleiotropic Benefits of Vitamin D in Patients With Diabetic Kidney Disease? A Systematic Review of Randomized Controlled Trials.

Abstract

Type 2 diabetes (T2D) and kidney disease are risk factors for vitamin D deficiency. Native forms of vitamin D have a lower risk of hypercalcemia than calcitriol, the active hormone. The enzyme responsible for activating native vitamin D is now known to be expressed throughout the body; therefore, native vitamin D may have clinically relevant effects in many body systems. The objective of this systematic review was to examine the effect of native vitamin D supplementation on clinical outcomes and surrogate laboratory measures in patients with T2D and diabetic kidney disease (DKD). Systematic review. Randomized controlled trials (RCTs) conducted in any country. Adults with T2D and DKD receiving supplementation with any form of native vitamin D (eg, ergocalciferol, cholecalciferol, calcifediol). Clinical outcomes and surrogate clinical and laboratory measures reported in each of the trials were included in this review. The following databases were searched from inception to January 31, 2023: Embase, MEDLINE, Cochrane CENTRAL, Web of Science, ProQuest Dissertations and Theses, and medRxiv. Only RCTs examining supplementation with a native vitamin D form with a control or placebo comparison group were included. We excluded studies reporting only vitamin D status or mineral metabolism parameters, without any other outcomes of clinical relevance or surrogate laboratory measures. Study quality was evaluated using the Cochrane risk-of-bias tool (RoB2). Results were synthesized in summary tables for each type of outcome with the P values from the original studies displayed. Nine publications were included, corresponding to 5 separate RCTs (377 participants total). Mean age ranged from 40 to 63. All trials administered vitamin D3. Intervention groups experienced improvements in vitamin D status and a reduction in proteinuria in 4 of the 5 included RCTs. There was a decrease in low-density lipoprotein and total cholesterol in the 2 trials in which they were measured. Improvements in bone mass, flow-mediated dilation, and inflammation were also reported, but each was only measured in 1 RCT. Effects on glucose metabolism, high-density lipoprotein, triglycerides, blood pressure, oxidative stress, and kidney function were mixed. No serious adverse effects were reported. Limitations include the small number of RCTs and lack of information on the use of drugs that affect measured outcomes (eg, proteinuria-lowering renin-angiotensin-aldosterone system inhibitors and lipid-lowering medication) in most studies. Our study is also limited by the absence of a prestudy protocol and registration. Native vitamin D is a safe treatment that improves vitamin D status in patients with DKD. Vitamin D may modify proteinuria and lipid metabolism in DKD, but further well-designed trials that include well-established treatments are necessary. Overall, there is limited evidence for beneficial pleiotropic effects of vitamin D in patients with DKD.