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Ngozi R Mbanefo,1 Samuel N Uwaezuoke,1 Chizoma I Eneh,2 Chioma L Odimegwu,1 Ugo N Chikani,1 Uzoamaka V Muoneke,1 Charles E Nwolisa,3 Kenneth E Odo,1 Francis N Ogbuka,2 Anthony T Akwue4 1Department of Pediatrics, the University of Nigeria Teaching Hospital Ituku-Ozalla Enugu, Enugu, Nigeria; 2Department of Pediatrics, Enugu State University Teaching Hospital Enugu, Enugu, Nigeria; 3Department of Pediatrics, Federal Medical Centre, Owerri, Imo State, Nigeria; 4Emergency Department, ASEER Field Hospital, Al Rabwah, Kingdom of Saudi ArabiaCorrespondence: Samuel N Uwaezuoke, Tel +2348033248108, Email snuwaezuoke@yahoo.comIntroduction: Frequent relapses and steroid dependence are common treatment challenges of steroid-sensitive nephrotic syndrome (SSNS) in children. Acute respiratory infection (ARI) is the most frequently reported trigger of relapse. Given the role of zinc supplementation in preventing ARI, some studies show that this targeted intervention may reduce relapses in childhood SSNS.Aim: This systematic review aimed to determine if oral zinc supplementation can significantly reduce relapses in this disease.Methods: We searched the PubMed and Google Scholar electronic databases for interventional and observational analytical studies without limiting their year or language of publication. We selected studies with primary data that met our inclusion criteria, screened their titles and abstracts, and removed duplicates. We used a preconceived structured form to extract data items from selected studies and conducted a quality assessment of randomized controlled trials (RCTs) and non-randomized studies with the Cochrane collaboration tool and the Newcastle Ottawa Scale, respectively. We qualitatively synthesized the extracted data to validate the review’s objective.Results: Eight full-text articles were selected, comprising four RCTs and four observational analytical studies. Two of the RCTs had a high risk of bias in three parameters of the Cochrane collaboration tool, while three non-randomized studies had low methodological quality. A total of 621 pediatric patients with SSNS were investigated in the eight studies: six participants dropped out in one study. Three RCTs indicate that zinc supplementation may lead to sustained remission or reduction in relapse rate. Similarly, three observational analytical studies suggest a significant relationship between reduced serum zinc levels and disease severity.Conclusion: Despite the association of zinc deficiency with increased morbidity in SSNS and the reduction of relapse rates with zinc supplementation, there is no robust evidence to recommend its use as a therapeutic adjunct. We recommend more adequately-powered RCTs to strengthen the current evidence.Keywords: acute respiratory infection, frequent relapses, nephrotic syndrome, childhood, zinc supplementation