METHODS: Case series.
METHODS: 818 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.
METHODS: Genetic 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.
CONCLUSIONS: Missing data, and 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.
UNASSIGNED: The 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.
方法:案例系列。
方法:在西班牙51个CKDUE中心的818名年龄≤45岁的患者,和估计的GFR<15mL/min/1.73m2或维持透析或移植治疗。
方法:使用高通量测序(HTS)对529个与遗传性肾病相关的基因进行基因检测。在203例(24.8%)患者中检测到与遗传模式一致的致病性和/或可能致病性(P/LP)基因变异。IV型胶原基因的变异是最常见的(COL4A5,COL4A4,COL4A3;35%的总基因变异),其次是NPHP1,PAX2,UMOD,MUC1和INF2(7.3%,5.9%,2.5%,分别为2.5%和2.5%)。总的来说,鉴定了87个被分类为P/LP的新变体。最常见的5种以前未诊断的疾病是Alport综合征谱(占总阳性报告的35%)。遗传性足细胞病(19%),肾单位(11%),常染色体显性肾小管间质性肾病(7%)和先天性肾脏和泌尿道异常(CAKUT:5%)。191名(23.3%)参与者和65/203名(32.0%)P/LP变异患者报告了肾病家族史。
结论:数据缺失。自愿入学导致的选择偏差。
结论:HTS的基因组检测在大约四分之一的年轻CKDUE和晚期肾脏疾病患者中发现了肾脏疾病的遗传原因。这些发现表明,遗传研究是评估CKDUE患者的潜在有用工具。