Schott Clara, Alajmi Mohammad, Bukhari Mohammad, Relouw Sydney, Wang Jian, McIntyre Adam D, Baker Cadence, Colaiacovo Samantha, Campagnolo Carla, Almada Offerni Gabriela, Blake Peter G, Chiu Micheal, Cowan Andrea, Garg Amit X, Gunaratnam Lakshman, House Andrew A, Huang Shih-Han Susan, Iyer Hariharan, Jain Arsh K, Jevnikar Anthony M, Johnson John, Lotfy Khaled, Moist Louise, Rehman Faisal, Roshanov Pavel S, Sultan Nabil, Weir Matthew A, Basharat Pari, Florendo-Cumbermack Anita, Khan Tayyab, Thain Jenny, Kidd Kendrah, Kmoch Stanislav, Bleyer Anthony J, Bhangu Jaspreet, Hegele Robert A, Connaughton Dervla M
Department of Biochemistry, Schulich School of Medicine & Dentistry, Western University, 1151 Richmond St., London, ON N6A 5C1, Canada.
Department of Medicine, Division of Nephrology, London Health Sciences Centre, London, ON N6A 5A5, Canada.
Genes (Basel). 2025 Mar 31;16(4):408. doi: 10.3390/genes16040408.
Genetic causes of chronic diseases, once considered rare in adult-onset disease, now account for between 10 and 20% of cases of chronic kidney disease (CKD). Confirming a genetic diagnosis can influence disease management; however, the utility of genetic testing in older adults remains poorly understood, partly due to age-based restrictions on testing access. To better evaluate the diagnostic yield and clinical utility of genetic testing in this population, we analyzed data from adults aged ≥50 years with CKD who were assessed in a specialized kidney genetics clinic. We studied a cohort of 125 adults with CKD aged ≥50 years at the time of genetic testing. Genetic testing included gene panels targeting disease-related genes based on clinical phenotype, and/or exome sequencing for additional monogenic causes if the initial panel testing was inconclusive. Pathogenic variants in disease-related genes were identified in 38% of patients. The highest diagnostic yield (48%) was in patients aged 50-54 years. The most common diagnosis post-testing was glomerulopathies (32%). Clinical utility, shown through the case series, included modifications to treatment and clinical management, as well as a reduction in the diagnostic odyssey. Our findings from a dedicated Kidney Genetics Clinic show that genetic testing in adults ≥50 years with CKD has significant diagnostic and clinical utility. These results support guideline recommendations that there should be no upper age limit for genetic testing. Future research in unselected CKD populations is needed to establish the broader applicability and feasibility of genetic testing in older adults.
慢性疾病的遗传病因，曾被认为在成人发病的疾病中较为罕见，如今在慢性肾脏病（CKD）病例中占比达10%至20%。确诊遗传诊断可影响疾病管理；然而，基因检测在老年人中的效用仍知之甚少，部分原因是基于年龄的检测准入限制。为了更好地评估该人群基因检测的诊断率和临床效用，我们分析了在一家专门的肾脏遗传学诊所接受评估的≥50岁CKD成人的数据。我们研究了一组125名在基因检测时年龄≥50岁的CKD成人。基因检测包括根据临床表型针对疾病相关基因的基因panel，和/或如果初始panel检测无定论则进行外显子组测序以寻找其他单基因病因。在38%的患者中鉴定出疾病相关基因的致病变异。诊断率最高（48%）的是50 - 54岁的患者。检测后最常见的诊断是肾小球病（32%）。通过病例系列显示的临床效用包括治疗和临床管理的调整，以及诊断探索过程的缩短。我们在一家专门的肾脏遗传学诊所的研究结果表明，对≥50岁的CKD成人进行基因检测具有显著的诊断和临床效用。这些结果支持了指南中关于基因检测不应设年龄上限的建议。需要对未经过筛选的CKD人群进行未来研究，以确定基因检测在老年人中的更广泛适用性和可行性。
