Non‐corticosteroid immunosuppressive medications for steroid‐sensitive nephrotic syndrome in children

Background About 80% of children with steroid‐sensitive nephrotic syndrome (SSNS) have relapses. Of these children, half relapse frequently, and are at risk of adverse effects from corticosteroids. While non‐corticosteroid immunosuppressive medications prolong periods of remission, they have significant potential adverse effects. Currently, there is no consensus about the most appropriate second‐line agent in children who are steroid sensitive, but who continue to relapse. In addition, these medications could be used with corticosteroids in the initial episode of SSNS to prolong the period of remission. This is the fourth update of a review first published in 2001 and updated in 2005, 2008 and 2013. Objectives To evaluate the benefits and harms of non‐corticosteroid immunosuppressive medications in SSNS in children with a relapsing course of SSNS and in children with their first episode of nephrotic syndrome. Search methods We searched the Cochrane Kidney and Transplant Register of Studies up to 10 March 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. Selection criteria Randomised controlled trials (RCTs) or quasi‐RCTs were included if they involved children with SSNS and compared non‐corticosteroid immunosuppressive medications with placebo, corticosteroids (prednisone or prednisolone) or no treatment; compared different non‐corticosteroid immunosuppressive medications or different doses, durations or routes of administration of the same non‐corticosteroid immunosuppressive medication. Data collection and analysis Two authors independently assessed study eligibility, risk of bias of the included studies and extracted data. Statistical analyses were performed using a random‐effects model and results expressed as risk ratio (RR) for dichotomous outcomes or mean difference (MD) for continuous outcomes with 95% confidence intervals (CI). The certainty of the evidence was assessed using GRADE. Main results We identified 43 studies (91 reports) and included data from 2428 children. Risk of bias assessment indicated that 21 and 24 studies were at low risk of bias for sequence generation and allocation concealment respectively. Nine studies were at low risk of performance bias and 10 were at low risk of detection bia