Effect of Vitamin D Receptor Activators on Glomerular Filtration Rate: A Meta-Analysis and Systematic Review.

Qian Zhang,Ming Li,Tiansong Zhang,Jing Chen,Paolo Cravedi

doi:10.1371/journal.pone.0147347

Abstract

BackgroundVitamin D receptor activators (VDRAs) can protect against mineral bone disease, but they are reported to elevate serum creatinine (SCr) and may also reduce glomerular filtration rate (GFR).MethodsWe conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) to evaluate the effect of VDRAs on kidney function and adverse events. MEDLINE, EMBASE, the Cochrane Controlled Trials Register were searched for RCTs that evaluate vitamin D receptor activators (alfacalcidol, calcitriol, doxercalciferol, falecalcitriol, maxacalcitol and paricalcitol) up to March 2015.ResultsWe included 31 studies, all of which were performed between 1976 and 2015, which enrolled 2621 patients. Patients receiving VDRAs had lower eGFR (weighted mean difference WMD -1.29 mL/min /1.73 m2, 95% CI -2.42 to -0.17) and elevated serum creatinine (WMD 7.03 μmol/L, 95% CI 0.61 to 13.46) in sensitivity analysis excluding studies with dropout rate more than 30%. Subgroup analysis of the 5 studies that not use SCr-based measures did not indicated lower GFR in the VDRAs group(WMD -0.97 mL/min/1.73 m2, 95% CI -4.85 to 2.92). Compared with control groups, there was no difference in all-cause mortality (relative risk RR 1.41, 95% CI 0.58 to 3.80), cardiovascular disease (RR 0.84, 95% CI 0.42 to 1.71), and severe adverse events (RR 1.15, 95% CI 0.75 to 1.77) for the VDRAs groups. Episodes of hypercalcemia (RR 3.29, 95% CI 2.02 to 5.38) were more common in the VDRAs group than in the control group.ConclusionsAdministration of VDRAs increased serum creatinine levels. Subgroup analysis of studies that did not use SCr-based measures did not indicate a lower GFR in the VDRA group. Future studies with non-SCr-based measures are needed to assess whether the mild elevations of serum creatinine are of clinical significance.

Highlights

Vitamin D is synthesized in the skin or ingested in the diet
Patients receiving Vitamin D receptor activators (VDRAs) had lower estimated glomerular filtration rate (eGFR) and elevated serum creatinine (WMD 7.03 μmol/L, 95% confidence intervals (CIs) 0.61 to 13.46) in sensitivity analysis excluding studies with dropout rate more than 30%
Subgroup analysis of the 5 studies that not use serum creatinine (SCr)-based measures did not indicated lower glomerular filtration rate (GFR) in the VDRAs group(WMD -0.97 mL/min/1.73 m2, 95% CI -4.85 to 2.92)

Summary

Introduction

Vitamin D is synthesized in the skin or ingested in the diet. It is subsequently converted to the active metabolite 1,25(OH) vitamin D [1]. The consequences of vitamin D deficiency are secondary hyperparathyroidism and bone loss, leading to osteoporosis and fractures, mineralization defects, causing falls and fractures [2]. Vitamin D receptor activators (VDRA), such as calcitriol, paricalcitol, or doxercalciferol, have been developed to treat osteoporosis, chronic kidney disease-mineral and bone disorder (CKD-MBD), and can reduce podocyte injury, modulate immune responses, and improve insulin sensitivity [3,4,5,6]. Patients given high-dose paricalcitol (2 μg daily) experienced significant declines in estimated glomerular filtration rate (eGFR). Vitamin D receptor activators (VDRAs) can protect against mineral bone disease, but they are reported to elevate serum creatinine (SCr) and may reduce glomerular filtration rate (GFR)

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