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Genetic Characterization of Kidney Failure of Unknown Etiology in Spain: Findings From the GENSEN Study

2024; Elsevier BV; Volume: 84; Issue: 6 Linguagem: Inglês

10.1053/j.ajkd.2024.04.021

1523-6838

Miquel Blasco, Borja Quiroga, José Manuel García‐Aznar, Cristina Castro-Alonso, Saulo J. Fernández-Granados, Enrique Luna, Gema Fernández Fresnedo, Marta Ossorio, María Jesús Izquierdo, Didier Sánchez-Ospina, Laura Castañeda-Infante, Ricardo Mouzo, Mercedes Cao, María Lara Besada-Cerecedo, Ricardo Pan-Lizcano, Roser Torrá, Alberto Ortíz, Patricia de Sequera, Victoria E Garcia Montemayor, Mercedes Salgueira Lazo, Auxiliadora Mazuecos Blanca, Tamara Jiménez Salcedo, María José Espigares Huete, Elena Araceli Jiménez Vibora, Concepción Álamo Caballero, Eduardo Josué Banegas Derás, Alejandro Alonso Bethencourt, Ángel Alberto García Peña, Saulo Fernández Granados, Gema Fernández Fresnedo, Leonardo Calle García, Jesús Martín García, Jorge Estifan Kasabji, María Jesús Izquierdo, Ricardo Mouzo Mirco, Rebeca García-Agudo, Gabriel de Arriba, Carme Facundo Molas, Marc Xipell Font, Alejandra Yugueros González, Paula Antóns, Meritxell Ibernon Vilaro, Vanessa de la Fuente Fernández, Yariel González Galván, Antonio Cabezas, Cristina Castro Alonso, Isabel Juan García, Eduardo Garín Cascales, J. Morant, Enrique Luna Complejo, Rosa María Díaz Campillejo, Silvia González Sanchidrián, Mercedes Cao Vilariño Complejo, Milagros Sierra Carpio, Mayra Ortega Díaz, Rosa Sánchez Hernández, Marta Ossorio González, Almudena Vega Martínez, M Picasso, Elena Gomá-Garcés, Martín Giorgi, Patricia Martínez‐Miguel, Eduardo Gutiérrez Martínez, Vicente Paraíso Cuevas, Rocío Echarri, Víctor Martínez, Mireia Arnedo, L Infante, Jose Antonio Menacho Miguel,

Chronic Kidney Disease and Diabetes

Rationale & Objective Chronic kidney disease (CKD) of unknown etiology (CKDUE) is one of the main global causes of kidney failure. While genetic studies may identify an etiology in these patients, few studies have implemented genetic testing of CKDUE in population-based series of patients which was the focus of the GENSEN. Study Design Case series. Settings & Participants 818 patients aged ≤45 years at 51 Spanish centers with CKDUE, and either an estimated GFR <15 mL/min/1.73 m2 or treatment with maintenance dialysis or transplantation. Observations Genetic testing for 529 genes associated to inherited nephropathies using high-throughput sequencing (HTS). Pathogenic and/or likely pathogenic (P/LP) gene variants concordant with the inheritance pattern were detected in 203 (24.8%) patients. Variants in type IV collagen genes were the most frequent (COL4A5, COL4A4, COL4A3; 35% of total gene variants), followed by NPHP1, PAX2, UMOD, MUC1 and INF2 (7.3%, 5.9%, 2.5%, 2.5% and 2.5% respectively). Overall, 87 novel variants classified as P/LP were identified. The top 5 most common previously undiagnosed diseases were Alport syndrome spectrum (35% of total positive reports), genetic podocytopathies (19%), nephronophthisis (11%), autosomal dominant tubulointerstitial kidney disease (7%) and congenital anomalies of the kidney and urinary tract (CAKUT: 5%). Family history of kidney disease was reported by 191 (23.3 %) participants and by 65/203 (32.0%) patients with P/LP variants. Limitations Missing data. Selection bias resulting from voluntary enrollment. Conclusions Genomic testing with HTS identified a genetic cause of kidney disease in approximately one quarter of young patients with CKDUE and advanced kidney disease. These findings suggest that genetic studies are a potentially useful tool for the evaluation of people with CKDUE.