Zinc supplementation as an adjunct to standard therapy in childhood nephrotic syndrome - a systematic review

Abstract

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

Relationship between serum zinc and homocysteine in children with nephrotic syndrome

“…The balance of Th-1-Th-2 cytokines may prevent the occurrence of relapse in NS. 15 Homocysteine did not linearly correlate with zinc in our study. After controlling for age and albumin level, homocysteine was observed to have a significant association with zinc by a cubic model.…”

“…No zinc deficiency was observed in the first attack NS patients. Previous studies by Arun et al and Bhatt et al showed that zinc supplementation may decrease the incidence of relapse in NS patients, 15,16 due to the effect of zinc in reducing the risk of infection, particularly infection of the gastrointestinal and respiratory tracts.1 6 Zinc deficiency causes downregulation of Th1 cytokines, relative Th-2 bias, and increased risk of infection. Zinc supplementation strengthens IL-1 and interferon gene expression, thereby restoring the Th1 immune response.…”

Influence of zinc deficiency on one year recurrence in children with nephrotic syndrome

“…They established that addition of zinc to standard treatment of nephrotic syndrome is effective in decreasing of infections and recurrences. (15) Our study also showed that recurrences in nephrotic patients have a relationship between low plasma zinc levels.…”

Pediatric Nephrotic Syndrome: Pharmacologic and Nutrition Management

“…A recent meta‐analysis and systematic review of 6 studies evaluated the use of zinc in pediatric patients with SDNS or Frequently Relapsing Nephrotic Syndrome (FRNS) and suggests that zinc therapy added to standard therapy may reduce the number of relapses at 6 months and 12 months and may help induce remission 51 . Although the studies included were found to be of "very low quality," this presents an exciting area for future research on the effects of this micronutrient in pediatric NS 51 . Finally, urinary losses of vitamin B 12 and transcobalamin in pediatric NS have been described, but the impact of this on the development of anemia is unknown 47 …”