Scientific publications
Genetic Characterization of Kidney Failure of Unknown Etiology in Spain: Findings From the GENSEN Study. Scientific Publication
Miquel Blasco 1 , Borja Quiroga 2 , José M García-Aznar 3 , Cristina Castro-Alonso 4 , Saulo J Fernández-Granados 5 , Enrique Luna 6 , Gema Fernández Fresnedo 7 , Marta Ossorio 8 , María Jesús Izquierdo 9 , Didier Sanchez-Ospina 10 , Laura Castañeda-Infante 11 , Ricardo Mouzo 12 , Mercedes Cao 13 , María L Besada-Cerecedo 14 , Ricardo Pan-Lizcano 14 , Roser Torra 15 , Alberto Ortiz 16 , Patricia de Sequera 17 ; GENSEN study investigators
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.
CITATION Am J Kidney Dis. 2024 Jul 5:S0272-6386(24)00844-8. doi: 10.1053/j.ajkd.2024.04.021.
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