Nephrogenomics, precision medicine and the role of genetic testing in adult kidney disease management

Abstract

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.