Vitamin D Deficiency and Treatment Versus Risk of Infection in End-Stage Renal Disease Patients Under Dialysis

A Systematic Review and Meta-analysis

Guobin Su; Zhuangzhu Liu; Xindong Qin; Xu Hong; Xusheng Liu; Zehuai Wen; Bengt Lindholm; Juan-Jesus Carrero; David W Johnson; Nele Brusselaers; Cecilia Stålsby Lundborg

Disclosures

Nephrol Dial Transplant. 2019;34(1):146-156. 

In This Article

Abstract and Introduction

Abstract

Background: Infections are common and can be fatal in patients undergoing long-term dialysis. Recent studies have shown conflicting evidence associating infection with vitamin D status or use of vitamin D and have not been systematically reviewed in this population.

Methods: We searched PubMed, Web of Science, Cochrane Library, Embase and three Chinese databases from inception until December 2017 for interventional [non-randomized or randomized controlled trials (RCTs)], cohort and case–control studies on levels of serum 25-hydroxyvitamin D [25(OH)D] or use of vitamin D [supplemental nutritional vitamin D or vitamin D receptor activator (VDRA)] and infection (any infection, infection-required hospitalization or infection-related death or composite) in long-term dialysis patients. We conducted a meta-analysis on the relative risk (RR) of infection and level of 25(OH)D or use of vitamin D.

Results: Of 2440 reports identified, 17 studies met inclusion criteria, all with moderate quality, with 6 cohort studies evaluating 25(OH)D serum concentrations (n = 5714) and 11 (2 RCTs and 9 observational studies) evaluating the use of vitamin D (n = 92 309). The risk of composite infection was 39% lower {relative risk [RR] 0.61 [95% confidence interval (CI) 0.41–0.89]} in the subjects with high or normal levels of 25(OH)D than in those with low levels. When compared with those who did not use vitamin D, the pooled adjusted risk for composite infection was 41% lower in those who used vitamin D [RR 0.59 (95% CI 0.43–0.81)].

Conclusions: High or normal serum levels of 25(OH)D and the use of vitamin D, particularly VDRA, were each associated with a lower risk of composite infection in long-term dialysis patients.

Introduction

Infection is the second leading cause of death in patients with chronic kidney disease (CKD).[1,2] One potential reason for the heightened infection risk is a high prevalence of vitamin D deficiency {both the major circulating metabolite, 25-hydroxyvitamin D [25(OH)D] and activated vitamin D (1,25-dihydroxyvitamin D)} among patients with CKD, particularly in those receiving chronic dialysis, owing to dietary restrictions and deficient renal 1α-hydroxylase activity.[3] Vitamin D may play an important protective role against pathogens, given that 25(OH)D supports the induction of antimicrobial peptides in response to both viral and bacterial stimuli.[4] Moreover, vitamin D metabolites have also been reported to induce innate antimicrobial effects, including induction of autophagy and synthesis of both reactive nitrogen intermediates and reactive oxygen intermediates.[5]

In the general population, studies have shown that higher levels of 25(OH)D or the use of vitamin D supplements is associated with a lower risk of infection.[6,7] However, observational studies have shown conflicting evidence of this association in dialysis populations.[8–15] Although several systematic reviews have been performed to investigate the health-related outcomes of vitamin D, such as all-cause mortality, cardiovascular disease and fractures in dialysis patients,[16–21] none of these has focused on the relationship between vitamin D status or treatment and infection in this population.

Therefore we performed a systematic review to explore the association between circulating vitamin D concentrations and the risk of infection [any infection, infection-related hospitalization (IRH) or infection-related death] in patients with end-stage kidney disease (ESKD) treated with chronic dialysis. We also explored whether the use of vitamin D supplements or vitamin D receptor activators (VDRAs) affected these outcomes.

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