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Genotype–phenotype correlations and nephroprotective effects of RAAS inhibition in patients with autosomal recessive Alport syndrome
BACKGROUND: Autosomal recessive Alport syndrome (ARAS) is caused by pathogenic variants in both alleles of either COL4A3 or COL4A4 genes. Reports on ARAS are rare due to small patient numbers and there are no reports on renin-angiotensin-aldosterone system (RAAS) inhibition therapy in ARAS. METHODS:...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer Berlin Heidelberg
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370956/ https://www.ncbi.nlm.nih.gov/pubmed/33772369 http://dx.doi.org/10.1007/s00467-021-05040-9 |
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author | Zhang, Yanqin Böckhaus, Jan Wang, Fang Wang, Suxia Rubel, Diana Gross, Oliver Ding, Jie |
author_facet | Zhang, Yanqin Böckhaus, Jan Wang, Fang Wang, Suxia Rubel, Diana Gross, Oliver Ding, Jie |
author_sort | Zhang, Yanqin |
collection | PubMed |
description | BACKGROUND: Autosomal recessive Alport syndrome (ARAS) is caused by pathogenic variants in both alleles of either COL4A3 or COL4A4 genes. Reports on ARAS are rare due to small patient numbers and there are no reports on renin-angiotensin-aldosterone system (RAAS) inhibition therapy in ARAS. METHODS: Retrospective study in 101 patients with ARAS from Chinese Registry Database of Hereditary Kidney Diseases and European Alport Registry. Genotype–phenotype correlations and nephroprotective effects of RAAS inhibition in ARAS were evaluated. RESULTS: Median age was 15 years (range 1.5–46 years). Twelve patients progressed to stage 5 chronic kidney disease (CKD5) at median age 20.5 years. Patients without missense variants had both higher prevalence and earlier onset age of hearing loss, nephrotic-range proteinuria, more rapid decline of eGFR, and earlier onset age of CKD5 compared to patients with 1 or 2 missense variants. Most patients (79/101, 78%) currently are treated with RAAS inhibitors; median age at therapy initiation was 10 years and mean duration 6.5 ± 6.0 years. Median age at CKD5 for untreated patients was 24 years. RAAS inhibition therapy delayed CKD5 onset in those with impaired kidney function (T-III) to median age 35 years, but is undefined in treated patients with proteinuria (T-II) due to low number of events. No treated patients with microalbuminuria (T-I) progressed to CKD5. ARAS patients with 1 or 2 missense variants showed better response to treatment than patients with non-missense-variants. CONCLUSIONS: Our study provides the first evidence for early use of RAAS inhibition therapy in patients with ARAS. Furthermore, genotype in ARAS correlates with response to therapy in favor of missense variants. |
format | Online Article Text |
id | pubmed-8370956 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-83709562021-08-31 Genotype–phenotype correlations and nephroprotective effects of RAAS inhibition in patients with autosomal recessive Alport syndrome Zhang, Yanqin Böckhaus, Jan Wang, Fang Wang, Suxia Rubel, Diana Gross, Oliver Ding, Jie Pediatr Nephrol Original Article BACKGROUND: Autosomal recessive Alport syndrome (ARAS) is caused by pathogenic variants in both alleles of either COL4A3 or COL4A4 genes. Reports on ARAS are rare due to small patient numbers and there are no reports on renin-angiotensin-aldosterone system (RAAS) inhibition therapy in ARAS. METHODS: Retrospective study in 101 patients with ARAS from Chinese Registry Database of Hereditary Kidney Diseases and European Alport Registry. Genotype–phenotype correlations and nephroprotective effects of RAAS inhibition in ARAS were evaluated. RESULTS: Median age was 15 years (range 1.5–46 years). Twelve patients progressed to stage 5 chronic kidney disease (CKD5) at median age 20.5 years. Patients without missense variants had both higher prevalence and earlier onset age of hearing loss, nephrotic-range proteinuria, more rapid decline of eGFR, and earlier onset age of CKD5 compared to patients with 1 or 2 missense variants. Most patients (79/101, 78%) currently are treated with RAAS inhibitors; median age at therapy initiation was 10 years and mean duration 6.5 ± 6.0 years. Median age at CKD5 for untreated patients was 24 years. RAAS inhibition therapy delayed CKD5 onset in those with impaired kidney function (T-III) to median age 35 years, but is undefined in treated patients with proteinuria (T-II) due to low number of events. No treated patients with microalbuminuria (T-I) progressed to CKD5. ARAS patients with 1 or 2 missense variants showed better response to treatment than patients with non-missense-variants. CONCLUSIONS: Our study provides the first evidence for early use of RAAS inhibition therapy in patients with ARAS. Furthermore, genotype in ARAS correlates with response to therapy in favor of missense variants. Springer Berlin Heidelberg 2021-03-27 2021 /pmc/articles/PMC8370956/ /pubmed/33772369 http://dx.doi.org/10.1007/s00467-021-05040-9 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article Zhang, Yanqin Böckhaus, Jan Wang, Fang Wang, Suxia Rubel, Diana Gross, Oliver Ding, Jie Genotype–phenotype correlations and nephroprotective effects of RAAS inhibition in patients with autosomal recessive Alport syndrome |
title | Genotype–phenotype correlations and nephroprotective effects of RAAS inhibition in patients with autosomal recessive Alport syndrome |
title_full | Genotype–phenotype correlations and nephroprotective effects of RAAS inhibition in patients with autosomal recessive Alport syndrome |
title_fullStr | Genotype–phenotype correlations and nephroprotective effects of RAAS inhibition in patients with autosomal recessive Alport syndrome |
title_full_unstemmed | Genotype–phenotype correlations and nephroprotective effects of RAAS inhibition in patients with autosomal recessive Alport syndrome |
title_short | Genotype–phenotype correlations and nephroprotective effects of RAAS inhibition in patients with autosomal recessive Alport syndrome |
title_sort | genotype–phenotype correlations and nephroprotective effects of raas inhibition in patients with autosomal recessive alport syndrome |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370956/ https://www.ncbi.nlm.nih.gov/pubmed/33772369 http://dx.doi.org/10.1007/s00467-021-05040-9 |
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