Cystic phenotype and chronic kidney disease in autosomal dominant Alport syndrome
© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA..
BACKGROUND AND HYPOTHESIS: Autosomal Dominant Alport Syndrome (ADAS), also known as Thin Basement Membrane Disease (TBMD), is caused by pathogenic variants in COL4A3 and COL4A4 genes. A cystic phenotype has been described in some patients with TBMD, but no genetic studies were performed. We conducted a genetic and radiologic investigation in a cohort of ADAS patients to analyze the prevalence of multicystic kidney disease (MKD) and its association with Chronic Kidney Disease (CKD).
METHODS: Retrospective single-center cohort study. Thirty-one patients showing pathogenic or likely pathogenic variants in COL4A3 or COL4A4 from a cohort of 79 patients with persistent microscopic hematuria were included. Mean follow-up was 9.4±9.6 years. The primary objective of the study was to determine the prevalence of MKD in the cohort of ADAS patients. Secondary objectives were to determine risk factors associated with an eGFR<45 ml/min/1.73m2 at the time of genetic and radiologic evaluation and to investigate the coexistence of other genetic abnormalities associated with familial hematuria and cystic kidney disease.
RESULTS: MKD was found in 16 patients (52%). Mean number of cysts per kidney was 12.7±5.5. No genetic abnormalities were found in a panel of 101 other genes related to familial hematuria, focal segmental glomerulosclerosis and cystic kidney disease. A greater number of patients with MKD had an eGFR<45 ml/min/1.73m2 (63% vs 7%, p=0.006) and more advanced CKD than patients without MKD. The annual rate of eGFR decline was greater in patients with MKD: -1.8 vs 0.06 ml/min/1.73m2/year (p=0.009). By multivariable linear regression analysis, the main determinants of eGFR change per year were time-averaged proteinuria (p=0.002) and MKD (p=0.02).
CONCLUSION: MKD is commonly found in ADAS and is associated with a worse kidney outcome. No pathogenic variants were found in genes other than COL4A3/COL4A4.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association - (2024) vom: 04. Jan. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bada-Bosch, Teresa [VerfasserIn] |
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| Links: |
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| Themen: |
Autosomal dominant Alport syndrome |
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| Anmerkungen: |
Date Revised 05.01.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1093/ndt/gfae002 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM366692496 |
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| 100 | 1 | |a Bada-Bosch, Teresa |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Cystic phenotype and chronic kidney disease in autosomal dominant Alport syndrome |
| 264 | 1 | |c 2024 | |
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| 500 | |a Date Revised 05.01.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a © The Author(s) 2024. Published by Oxford University Press on behalf of the ERA. | ||
| 520 | |a BACKGROUND AND HYPOTHESIS: Autosomal Dominant Alport Syndrome (ADAS), also known as Thin Basement Membrane Disease (TBMD), is caused by pathogenic variants in COL4A3 and COL4A4 genes. A cystic phenotype has been described in some patients with TBMD, but no genetic studies were performed. We conducted a genetic and radiologic investigation in a cohort of ADAS patients to analyze the prevalence of multicystic kidney disease (MKD) and its association with Chronic Kidney Disease (CKD) | ||
| 520 | |a METHODS: Retrospective single-center cohort study. Thirty-one patients showing pathogenic or likely pathogenic variants in COL4A3 or COL4A4 from a cohort of 79 patients with persistent microscopic hematuria were included. Mean follow-up was 9.4±9.6 years. The primary objective of the study was to determine the prevalence of MKD in the cohort of ADAS patients. Secondary objectives were to determine risk factors associated with an eGFR<45 ml/min/1.73m2 at the time of genetic and radiologic evaluation and to investigate the coexistence of other genetic abnormalities associated with familial hematuria and cystic kidney disease | ||
| 520 | |a RESULTS: MKD was found in 16 patients (52%). Mean number of cysts per kidney was 12.7±5.5. No genetic abnormalities were found in a panel of 101 other genes related to familial hematuria, focal segmental glomerulosclerosis and cystic kidney disease. A greater number of patients with MKD had an eGFR<45 ml/min/1.73m2 (63% vs 7%, p=0.006) and more advanced CKD than patients without MKD. The annual rate of eGFR decline was greater in patients with MKD: -1.8 vs 0.06 ml/min/1.73m2/year (p=0.009). By multivariable linear regression analysis, the main determinants of eGFR change per year were time-averaged proteinuria (p=0.002) and MKD (p=0.02) | ||
| 520 | |a CONCLUSION: MKD is commonly found in ADAS and is associated with a worse kidney outcome. No pathogenic variants were found in genes other than COL4A3/COL4A4 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a autosomal dominant Alport syndrome | |
| 650 | 4 | |a chronic kidney disease | |
| 650 | 4 | |a multicystic kidney disease | |
| 700 | 1 | |a Sevillano, Angel M |e verfasserin |4 aut | |
| 700 | 1 | |a Teresa Sánchez-Calvin, María |e verfasserin |4 aut | |
| 700 | 1 | |a Palma-Milla, Carmen |e verfasserin |4 aut | |
| 700 | 1 | |a Alba de Cáceres, Ignacio |e verfasserin |4 aut | |
| 700 | 1 | |a Díaz-Crespo, Francisco |e verfasserin |4 aut | |
| 700 | 1 | |a Trujillo, Hernando |e verfasserin |4 aut | |
| 700 | 1 | |a Alonso, Marina |e verfasserin |4 aut | |
| 700 | 1 | |a Cases-Corona, Clara |e verfasserin |4 aut | |
| 700 | 1 | |a Shabaka, Amir |e verfasserin |4 aut | |
| 700 | 1 | |a Quesada-Espinosa, Juan Francisco |e verfasserin |4 aut | |
| 700 | 1 | |a Rosales, José Miguel Lezana |e verfasserin |4 aut | |
| 700 | 1 | |a Gutiérrez, Eduardo |e verfasserin |4 aut | |
| 700 | 1 | |a Fernández-Juárez, Gema |e verfasserin |4 aut | |
| 700 | 1 | |a Caravaca-Fontán, Fernando |e verfasserin |4 aut | |
| 700 | 1 | |a Praga, Manuel |e verfasserin |4 aut | |
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