Precision Medicine in Pediatric Nephrology: From Shared Clinical Phenotypes to Genotype-Guided Diagnosis and Management

Vollständiger Abstract

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Pediatric nephrology is shifting from broad phenotype-based labels toward molecularly defined, genotype-guided diagnosis and management. Childhood kidney disorders are enriched for monogenic causes, yet persistent microscopic hematuria, bilateral kidney cysts, steroid-resistant nephrotic syndrome, and thrombotic microangiopathy may represent shared endpoints of biologically distinct mechanisms. Using these four scenarios, this narrative review illustrates how structured phenotyping, pedigree analysis, biochemical evaluation, and appropriately selected genomic testing can establish etiology, revise diagnoses, and guide clinical decision-making. Molecular diagnosis may support early nephroprotection, prevent ineffective immunosuppression, reveal tumor or extrarenal risks, enable mechanism-based therapy, and optimize transplantation planning. It also enables cascade testing, reproductive counseling, presymptomatic evaluation of relatives, and safer assessment of living-related donors. Genomic findings, however, require clinical context. Variants must be evaluated against gene–disease validity, inheritance, segregation, molecular mechanism, and phenotype, while variants of uncertain significance should not independently determine treatment or donor eligibility. Negative or inconclusive findings should prompt phenotypic reassessment, evaluation of analytical limitations, targeted studies, and periodic genomic reanalysis. Emerging genome and long-read sequencing, multiomics, artificial intelligence, and RNA-based therapeutics may further expand precision care, but rigorous interpretation, equitable access, appropriate counseling, and multidisciplinary collaboration remain essential. Precision nephrology derives value not from identifying variants alone, but from converting molecular etiology into safer, anticipatory, and individualized care.