Challenging the narrative of alport syndrome spectrum: no link with cystic phenotype

Alport Syndromes (AS) are the second leading genetic cause of Kidney Failure (KF). Whether multiple kidney cysts (MKC) phenotype belongs to the AS spectrum remains debated. This multicenter retrospective study focused on patients genotyped with pathogenic COL4A3, COL4A4, or COL4A5 variants (classifi...

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Published in:Nephrology, dialysis, transplantation dialysis, transplantation, 2024-12
Main Authors: Pagniez, Marie-Sophie, Lombardi, Yannis, Fages, Victor, Larrue, Romain, Laboux, Timothée, Gatinois, Clémence, Letavernier, Emmanuel, Rigothier, Claire, Glowacki, François, Mesnard, Laurent, Robert, Thomas
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container_title Nephrology, dialysis, transplantation
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creator Pagniez, Marie-Sophie
Lombardi, Yannis
Fages, Victor
Larrue, Romain
Laboux, Timothée
Gatinois, Clémence
Letavernier, Emmanuel
Rigothier, Claire
Glowacki, François
Mesnard, Laurent
Robert, Thomas
description Alport Syndromes (AS) are the second leading genetic cause of Kidney Failure (KF). Whether multiple kidney cysts (MKC) phenotype belongs to the AS spectrum remains debated. This multicenter retrospective study focused on patients genotyped with pathogenic COL4A3, COL4A4, or COL4A5 variants (classified as ACMG-AMP 4 or 5) between January 2011 and January 2023 across four French university hospitals. The study aimed to compare characteristics between two groups based on the presence or absence of MKC, defined by three or more cysts per kidney. The MKC group was compared to a control group with negative exome sequencing results for undetermined kidney disease (ES-UKD) to assess the association between MKC and AS. Among the 257 AS patients included, 38 (14.8%) presented MKC without variation from hereditary cystic kidney panel. MKC showed a significant association with male gender (p=0.004), cardiovascular risk factors, and loss of function variants (p=0.012). KF onset appeared significantly later, by 6 years, in MKC patients (p=0.035). Comparison with ES-UKD (n=990) control group showed no significant association between AS and MKC by univariate and multivariate analysis. Multivariate analysis identified patient age and male gender (p
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title Challenging the narrative of alport syndrome spectrum: no link with cystic phenotype
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