Article
Author: Cabezas, Antonio ; Mouzo Mirco, Ricardo ; Gutiérrez Martínez, Eduardo ; González Sanchidrián, Silvia ; Sierra Carpio, Milagros ; Martínez, Víctor ; Banegas Deras, Eduardo J. ; Mouzo, Ricardo ; Rodríguez García, Alejandra ; Jiménez Salcedo, Tamara ; Xipell Font, Marc ; González Galván, Yussel ; Álamo Caballero, Concepción ; Garín Cascales, Eduardo ; Juan García, Isabel ; Ortega Díaz, Mayra ; Blasco, Miquel ; García Agudo, Rebeca ; Antóns, Paula ; Ibernon Vilaro, Meritxell ; Echarri, Rocío ; Paraíso Cuevas, Vicente ; Giorgi, Martín ; Ortiz, Alberto ; Salgueira Lazo, Mercedes ; Sánchez Hernández, Rosa ; Araceli Jiménez Vibora, Elena ; Castro Alonso, Cristina ; Teresa López Picasso, María ; Pérez Arnedo, Mario ; Cao, Mercedes ; Goma, Elena ; Besada-Cerecedo, María L. ; Ossorio González, Marta ; Yugueros González, Alejandra ; Facundo Molas, Carme ; de Arriba de la Fuente, Gabriel ; de Sequera, Patricia ; Cao Vilariño Complejo, Mercedes ; Estifan Kasabji, Jorge ; José Espigares Huete, María ; Castro-Alonso, Cristina ; Sebastiá Morant, Josepa ; Izquierdo, María Jesús ; Castañeda-Infante, Laura ; Jesús Izquierdo, María ; Ossorio, Marta ; Sanchez-Ospina, Didier ; Martínez Miguel, Patricia ; Quiroga, Borja ; García-Aznar, José M. ; Luna Complejo, Enrique ; Pan-Lizcano, Ricardo ; de la Fuente Fernández, Vanessa ; Vega Martínez, Almudena ; Fernández-Granados, Saulo J. ; Fernández Fresnedo, Gema ; Fernández Granados, Saulo ; Antonio Menacho Miguel, Jose ; Martín García, Jesús ; Alonso Bethencourt, Alejandro ; Torra, Roser ; Calle García, Leonardo ; María Díaz Campillejo, Rosa ; Luna, Enrique ; Eugenia García Montemayor, Victoria ; Juliana Castañeda Infante, Laura ; Mazuecos Blanca, Auxiliadora
RATIONALE & OBJECTIVEChronic kidney disease of unknown etiology (CKDUE) is one of the main global causes of kidney failure. Genetic studies may identify an etiology in these patients, but few studies have implemented genetic testing of CKDUE in a population-based series of patients, which was the focus of the GENSEN Study.STUDY DESIGNCase series.SETTINGS & PARTICIPANTS818 patients aged≤45 years at 51 Spanish centers with CKDUE, and either an estimated glomerular filtration rate of<15mL/min/1.73m2 or treatment with maintenance dialysis or transplantation.OBSERVATIONSGenetic testing for 529 genes associated with 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 patients (24.8%). 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%). A family history of kidney disease was reported by 191 participants (23.3%) and by 65 of 203 patients (32.0%) with P/LP variants.LIMITATIONSMissing data, and selection bias resulting from voluntary enrollment.CONCLUSIONSGenomic 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.PLAIN-LANGUAGE SUMMARYThe cause of kidney disease is unknown for 1 in 5 patients requiring kidney replacement therapy, reflecting possible prior missed treatment opportunities. We assessed the diagnostic utility of genetic testing in children and adults aged≤45 years with either an estimated glomerular filtration rate of<15mL/min/1.73m2 or treatment with maintenance dialysis or transplantation. Genetic testing identified the cause of kidney disease in approximately 1 in 4 patients without a previously known cause of kidney disease, suggesting that genetic studies are a potentially useful tool for the evaluation of these patients.
