Calcineurin inhibitors in nephrotic syndrome secondary to podocyte gene mutations: a systematic review

Background Calcineurin inhibitor (CNI) use in genetic steroid-resistant nephrotic syndrome (SRNS) is controversial as response rate is reported to be lower than non-genetic disease and no plausible mechanism of action is known. Methods We reviewed PubMed for publications on CNI use in hereditary SRNS to determine (1) CNI response rate; (2) impact of response on renal outcome; and (3) clinical and molecular predictors of response. Variant pathogenicity was assessed according to American College of Medical Genetics criteria and patients were assigned to 1 of 4 categories based on estimated genotype contribution to phenotype. Cases with non-existing phenotype-to-genotype contribution were excluded. Subgroup analysis was performed for the possible and confirmed genetic cases. Results Data of 178 genetic SRNS cases from 22 studies were analyzed; 35% responded (fully or partially) to CNI with minimal change being the commonest biopsy pattern among responders. Full responders had superior kidney survival compared with partial and non-responders (log-rank test χ 2 = 10.7; P