Abstract：
OBJECTIVE: Chronic 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.
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.
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.
摘要：
目的：病因不明的慢性肾脏病（CKDUE）是全球肾衰竭的主要病因之一。虽然遗传研究可以确定这些患者的病因，很少有研究在基于人群的患者系列中实施CKDUE的基因检测,这是GENSEN的重点。
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。
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。
