Does Native Vitamin D Supplementation Have Pleiotropic Effects in Patients with End-Stage Kidney Disease? A Systematic Review of Randomized Trials

Abstract

Vitamin D has been shown to have multiple pleiotropic effects beyond bone and mineral metabolism, with purported roles in cardiovascular disease, cancer, and host immunity. Vitamin D deficiency is common in patients with end-stage kidney disease (ESKD); however, current clinical practice has favored the use of the active hormone. Whether vitamin D deficiency should be corrected in patients with ESKD remains unclear, as few randomized trials have been conducted. In this systematic review, we summarize the current evidence examining whether vitamin D supplementation improves outcomes, beyond mineral metabolism, in patients with ESKD. Data from randomized controlled trials of adults with ESKD were obtained by searching Ovid MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and the Web of Science Core Collection from inception to February 2023. Twenty-three trials composed of 2489 participants were identified for inclusion. Data were synthesized by two independent reviewers and summarized in tables organized by outcome. Outcomes included measures of mortality, cardiovascular disease, inflammation, muscle strength/function, nutrition, patient well-being, and outcomes specific to ESKD including erythropoietin usage, pruritus, and dialysis access maturation. The Cochrane risk of Bias Tool (RoB 2, 2019) was used to assess study quality. Overall, our findings indicate a minimal and varied benefit of native vitamin D supplementation. From the largest studies included, we determine that vitamin D has no demonstrated effect on patient-reported measures of well-being or utilization of erythropoietin, nor does it change levels of the inflammation biomarker C-reactive protein. Included trials were heterogeneous with regards to outcomes, and the majority studied small participant populations with a relatively short follow-up. We conclude that vitamin D supplementation corrects vitamin D deficiency and is safe and well-tolerated in humans with ESKD. However, it is not clear from clinical trials conducted to date that a causal pathway exists between 25(OH)D and pleiotropic effects that is responsive to vitamin D treatment.

Vitamin D levels in the pre- and post-COVID-19 pandemic periods in pediatric patients with chronic kidney disease

“…In the present study, after the pandemic, the dose of cholecalciferol in 45% of the patients was ≤2,000 IU per day, so most probably the majority of patients had low serum levels of VD. However, in studies in CKD pediatric patients with VD supplementation at doses of 4,000 IU, 36 to 91% achieved levels >30 ng/mL (31,32); these data seem to correspond to our results, since despite cholecalciferol supplementation (up to 4,000 IU per day), at the end of follow-up only 47.4% reached VD sufficiency levels. The failure to achieve optimal VD levels, despite adequate supplementation, has been explained previously; Demburg et al reported that glomerular disease may be associated with changes in vitamin D metabolism that is affected by urinary losses of vitamin D-binding protein (VDBP) secondary to glomerular and/ or tubular damage in CKD (33).…”