Systematic Reviews
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Pediatr. Nov 8, 2016; 5(4): 383-390
Published online Nov 8, 2016. doi: 10.5409/wjcp.v5.i4.383
Zinc supplementation as an adjunct to standard therapy in childhood nephrotic syndrome - a systematic review
Girish Chandra Bhatt, Shikha Jain, Rashmi Ranjan Das
Girish Chandra Bhatt, Shikha Jain, Department of Pediatrics, All India Institute of Medical Sciences, Bhopal 462020, India
Rashmi Ranjan Das, Department of Pediatrics, All India Institute of Medical Sciences, Bhubaneswar 751019, India
Author contributions: Bhatt GC designed the research; Bhatt GC and Jain S wrote the paper; Bhatt GC and Das RR performed the research; Das RR analyzed the data and supervised the paper; all authors read and approved the final manuscript.
Conflict-of-interest statement: All the authors declare that they have no competing interests.
Data sharing statement: The technical appendix, statistical code, and dataset are available from the corresponding author at
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Rashmi Ranjan Das, MD, Department of Pediatrics, All India Institute of Medical Sciences, SIJUA, Bhubaneswar 751019, India.
Telephone: +91-674-2472215 Fax: +91-674-2472215
Received: March 16, 2016
Peer-review started: March 18, 2016
First decision: May 19, 2016
Revised: June 30, 2016
Accepted: August 15, 2016
Article in press: August 16, 2016
Published online: November 8, 2016

To evaluate the role of zinc as add on treatment to the “recommended treatment” of nephrotic syndrome (NS) in children.


All the published literature through the major databases including Medline/Pubmed, Embase, and Google Scholar were searched till 31st December 2015. Reference lists from the articles were reviewed to identify additional pertinent articles. Retrieved papers concerning the role of zinc in childhood NS were reviewed by the authors, and the data were extracted using a standardized data collection tool. Randomized trials (RCTs) comparing zinc vs placebo was included. Effect of zinc was studied in both steroid sensitive and steroid dependent/frequent relapsing NS. The primary outcome measure was the risk of relapse in 12 mo. The secondary outcome measures were mean relapse rate per patient in 12 mo, mean relapse rate per patient in 6 mo, risk of infection associated relapse in 12 mo, cumulative dose of steroids in two groups, mean length of time to next relapse, adverse effects of therapy, and change in serum zinc levels.


Of 54 citations retrieved, a total of 6 RCTs were included. Zinc was used at a dose of 10-20 mg/d, for the duration that varied from 6-12 mo. Compared to placebo, zinc reduced the frequency of relapses, induced sustained remission/no relapse, reduced the proportion of infection episodes associated with relapse with a mild adverse event in the form of metallic taste. The GRADE evidence generated was of “very low-quality”.


Zinc may be a useful additive in the treatment of childhood NS. The evidence generated mostly was of “very low-quality”. We need more good quality RCTs in different country setting as well different subgroups of children before any firm recommendation can be made.

Keywords: Nephrotic syndrome, Pediatric, Relapse, Zinc, Micronutrient

Core tip: Relapses in nephrotic syndrome (NS) increase morbidity and mortality. Studies have shown that zinc deficiency is common in NS. Zinc deficiency might lead to down-regulation of T-helper 1 (Th1) cytokines, a relative T-helper 2 (Th2) bias, and an increased risk of infection. The later commonly associated with relapse in NS. Zinc supplementation restores Th1-Th2 imbalance and may decrease relapse. The primary aim of this review is to evaluate the efficacy of zinc in preventing relapses in childhood NS (steroid sensitive and steroid dependent/frequent relapsing). The secondary aim is to evaluate the safety of zinc supplementation in this regard.