Bensouna Ilias, Doreille Alice, Dancer Marine, Lebre Anne-Sophie, Robert Thomas, Mesnard Laurent
Soins Intensifs Néphrologiques et Rein Aigu (SINRA), Nephrology Department, Tenon Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.
Inserm UMR_S1155, Paris, France.
Nat Rev Nephrol. 2025 Jun 16. doi: 10.1038/s41581-025-00970-1.
Genetic investigations in nephrology have long been viewed as the prerogative of paediatricians or restricted to archetypal genetic nephropathies with highly penetrant variants affecting young adults. However, genetic testing has emerged as a pivotal tool in the field of adult nephrology, with the ability to revolutionize the understanding and management of adult kidney diseases. Here, we explore the multifaceted role of genomic testing (such as exome or genome sequencing) in chronic kidney disease, shedding light on current genetic findings for reframing diagnostic paradigms and tailoring treatment strategies. Genomic testing has enhanced our comprehension of kidney diseases of unknown origin by showing that ~20% are attributable to kidney Mendelian genetic disorders with as yet unsuspected phenocopies. Beyond genetic counselling, genetic integration can optimize therapeutic interventions, kidney transplantation and kidney disease prevention, both in index cases and in at-risk family members. Furthermore, the emerging field of rapid nephrogenomics promises streamlined diagnosis and management, with a potential impact on early therapeutic strategy. Importantly, although costs continue to decrease, the integration of genomic technologies in nephrology practice raises several ethical concerns, especially regarding variants of uncertain significance, and incidental or secondary findings. Establishing multidisciplinary frameworks should maximize the potential of nephrogenomics to improve patient outcomes.
长期以来，肾脏病学的遗传学研究一直被视为儿科医生的特权，或者局限于那些影响年轻人、具有高外显率变异的典型遗传性肾病。然而，基因检测已成为成人肾脏病学领域的关键工具，能够彻底改变对成人肾脏疾病的理解和管理。在此，我们探讨基因组检测（如外显子组或基因组测序）在慢性肾脏病中的多方面作用，揭示当前的遗传学发现，以重塑诊断模式并制定个性化治疗策略。基因组检测通过表明约20%的不明原因肾脏疾病可归因于具有尚未被怀疑的表型模拟的孟德尔遗传性肾脏疾病，增强了我们对这类疾病的理解。除了遗传咨询外，基因整合可以优化治疗干预、肾脏移植和肾脏疾病预防，无论是在索引病例还是高危家庭成员中。此外，快速肾脏基因组学这一新兴领域有望实现简化诊断和管理，对早期治疗策略产生潜在影响。重要的是，尽管成本持续下降，但基因组技术在肾脏病学实践中的整合引发了一些伦理问题，尤其是关于意义不确定的变异以及偶然或次要发现。建立多学科框架应能最大限度地发挥肾脏基因组学改善患者预后的潜力。
