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11.05.2020 | Original Article

COL4A3 mutation is an independent risk factor for poor prognosis in children with Alport syndrome

verfasst von: Gulsah Ozdemir, Bora Gulhan, Emine Atayar, Seha Saygılı, Oguz Soylemezoglu, Zeynep Birsin Ozcakar, Fehime Kara Eroglu, Cengiz Candan, Belde Kasap Demir, Alper Soylu, Selçuk Yüksel, Harika Alpay, Ayse Agbas, Ali Duzova, Mutlu Hayran, Fatih Ozaltin, Rezan Topaloglu

Erschienen in: Pediatric Nephrology | Ausgabe 10/2020

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Abstract

Background

Alport syndrome (AS) is an inherited glomerular disease caused by mutations in COL4A3, COL4A4, or COL4A5. Associations between clinical manifestations and genotype are not yet well defined. Our study aimed to define clinical and genetic characteristics, establish genotype–phenotype correlations, and determine prognosis of AS in children.

Methods

A total of 87 children with AS from 10 pediatric nephrology centers, whom had genetic analyses performed at the Hacettepe University Nephrogenetics Laboratory between February 2017 and February 2019, were included. Data regarding demographics, family history, clinical and laboratory characteristics, histopathological and genetic test results, treatments, and yearly follow-up results were retrospectively analyzed.

Results

Of 87 patients, 16% presented with nephrotic syndrome. In patients with nephrotic syndrome, kidney biopsy findings showed focal segmental glomerulosclerosis (FSGS) in 79%, and COL4A3 mutations were the leading genetic abnormality (50%). Twenty-four percent of all patients progressed to chronic kidney disease (CKD). The rate of progression to CKD and the decline in the glomerular filtration rate of the patients with COL4A3 mutation were higher than other mutation groups (p < 0.001 and p = 0.04, respectively). In kidney survival analysis, nephrotic syndrome presentation, histopathology of FSGS, COL4A3 mutations, and autosomal recessive inheritance were found as independent risk factors for earlier progression to CKD. Cyclosporin A treatment did not improve kidney survival.

Conclusions

We emphasize that genetic testing is important for patients suspected as having AS. Furthermore, COL4A mutations should be considered in patients with FSGS and steroid-resistant nephrotic syndrome. This approach will shed light on the prognosis of patients and help with definitive diagnosis, preventing unnecessary and potentially harmful medications.

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Titel: COL4A3 mutation is an independent risk factor for poor prognosis in children with Alport syndrome
verfasst von: Gulsah Ozdemir
Bora Gulhan
Emine Atayar
Seha Saygılı
Oguz Soylemezoglu
Zeynep Birsin Ozcakar
Fehime Kara Eroglu
Cengiz Candan
Belde Kasap Demir
Alper Soylu
Selçuk Yüksel
Harika Alpay
Ayse Agbas
Ali Duzova
Mutlu Hayran
Fatih Ozaltin
Rezan Topaloglu
Publikationsdatum: 11.05.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: Pediatric Nephrology / Ausgabe 10/2020
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-020-04574-8

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COL4A3 mutation is an independent risk factor for poor prognosis in children with Alport syndrome

Abstract

Background

Methods

Results

Conclusions

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Background

Methods

Results

Conclusions

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