Chronic Kidney Disease in Children with Suspected Genetic Etiology: Diagnostic Yield and Clinical Implications

Background: Chronic kidney disease (CKD) in children is frequently associated with underlying genetic etiologies, particularly in cases with early onset, congenital anomalies, or multisystem involvement. The integration of molecular diagnostics into routine nephrological practice represents an important step toward personalized medicine in pediatric CKD. Methods: This retrospective observational study included 50 pediatric patients with CKD stages 2–5 and suspected hereditary etiology evaluated at a tertiary pediatric center. All patients underwent genetic testing using next-generation sequencing and/or chromosomal microarray analysis. Clinical characteristics, CKD stage, extrarenal manifestations, and disease progression were analyzed in relation to genetic findings. Associations between clinical variables and genetic diagnosis were assessed using appropriate statistical tests, including multivariable logistic regression. Results: A positive genetic diagnosis was identified in 28 patients (56%), including 21 monogenic disorders detected by next-generation sequencing and 7 pathogenic copy number variants identified by chromosomal microarray analysis. Extrarenal manifestations were present in 48% of patients and were significantly associated with a higher diagnostic yield (75% vs. 42.3%; OR = 4.09; 95% CI: 1.23–13.61; p = 0.007). Psychomotor delay was strongly associated with pathogenic copy number variants (p < 0.001). Patients with confirmed genetic etiologies exhibited significantly higher rates of CKD progression compared with genetically negative individuals (82.1% vs. 22.7%; OR = 15.64; 95% CI: 3.90–62.7; p < 0.001). In multivariable analysis, genetic diagnosis shows association with disease progression after adjustment for age and baseline renal function. Conclusions: Genetic testing provided a molecular diagnosis in more than half of children with CKD and suspected hereditary etiology. Extrarenal manifestations were strongly associated with a higher diagnostic yield, while confirmed genetic etiologies may be associated with CKD progression. These findings support the early integration of genetic diagnostics into the evaluation of pediatric CKD to improve prognostic assessment and enable more personalized management strategies.