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Pediatric Nephrology
Published in: Pediatric Nephrology 6/2021

01-06-2021 | Nephrotic Syndrome | Review

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

Authors: Georgia Malakasioti, Daniela Iancu, Kjell Tullus

Published in: Pediatric Nephrology | Issue 6/2021

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Abstract

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 χ2 = 10.7; P < 0.01). WT1 variant carriers were most likely to respond to CNI compared with any other mutation [OR 4.7 (2.0–11.3); P < 0.01].

Conclusions

These findings support the current recommendation for using CNI as first-line treatment for children with SRNS whilst genetic analyses are pending. This would allow assessment of treatment response even in cases later established as genetic ensuring that benefits on kidney function are balanced with treatment toxicity.
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Metadata
Title
Calcineurin inhibitors in nephrotic syndrome secondary to podocyte gene mutations: a systematic review
Authors
Georgia Malakasioti
Daniela Iancu
Kjell Tullus
Publication date
01-06-2021
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Nephrology / Issue 6/2021
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-020-04695-0

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