Genomic advances have transformed the landscape of genetic kidney diseases, enabling a shift from traditional phenotype-based diagnostics to molecularly precise classification. Large-scale genetic testing has revealed that approximately 10% of chronic kidney diseases are monogenic, significantly enhancing disease recognition and redefining epidemiological prevalence—most notably for autosomal dominant polycystic kidney disease, Alport syndrome, podocytopathies, and autosomal dominant tubulointerstitial kidney disease. Importantly, genetic diagnostics have clarified previously uncertain etiologies in both pediatric and adult populations, improving diagnosis, prognosis, and management. Integration of molecular genetics into nephrology has also exposed key limitations of phenotype-driven classification: the discordance of genotype–phenotype, single-gene variants with diverse clinical syndromes, and similar phenotypes by distinct genetic etiologies. This complexity highlights the risks of relying solely on clinical observation—such as inappropriate therapeutic choices or missed diagnoses—which can compromise patient outcomes. For instance, multiple renal cysts can result from various genetic disorders, and misclassification as autosomal dominant polycystic kidney disease may lead to inappropriate use of tolvaptan. Molecular diagnostics now enable precision medicine by guiding therapy, improving transplantation decisions, and facilitating genetic counseling. In parallel, innovative therapies targeting the DNA-RNA-protein-epigenetic axis are advancing toward mechanism-driven treatment and genuinely improved patient benefit. Nonetheless, critical gaps remain in variant interpretation, equitable access to testing, and translation from genetic discovery to clinical application. The ongoing evolution of multi-omics integration, robust variant curation, and targeted delivery platforms holds promise for further breakthroughs. Together, these developments aim to transform outcomes and standards of care for patients with genetic kidney diseases, marking an era of true precision nephrology.
Liu et al. (2026) studied this question.