Genetic Testing for Pediatric Kidney Disease

 When presenting before 25 years of age, CKD is often (49.1%) related to congenital abnormalities of the kidney or urinary tract (CAKUT). The types of congenital anomalies may include obstructive uropathy, dysplastic kidney, reflux nephropathy, or prune belly syndrome. Approximately 10.4% will have CKD due to steroid resistant nephrotic syndrome, notably focal segmental glomerulosclerosis, congenital nephrotic syndrome, membranous nephropathy, or Denys-Drash syndrome.  Chronic glomerulonephritis accounts for 8.1% of cases and may present as systemic lupus erythematosus nephritis, IgA nephritis, or membranoproliferative glomerulonephritis-Type I/II.  Other causes of early-onset CKD include renal cystic ciliopathies, hemolytic uremic syndrome, nephrolithiasis/nephrocalcinosis, or other/unknown causes. 

Genetic causes of chronic kidney disease (CKD)

While a clinical diagnosis is often made, many cases of early-onset kidney disease also have an underlying genetic cause. Genetic causes or conditions are generally inherited or arise early in development and are not contagious. Vivante and Hildebrant (2016) concluded that about 1 in 5 individuals with early-onset CKD have an identifiable cause.  Bekheirnia et al. (2021) identified a genetic cause for 51% of the patients referred to their Renal Genetics Clinic. Genetic conditions previously identified in children/adolescents include, but are not limited, to autosomal dominant polycystic kidney disease, Alport syndrome, renal cysts and diabetes syndrome, Dent disease, Fabry disease, PAX2-related focal segmental glomerulosclerosis, NPHP1-related nephronophthisis, cystinuria, and hereditary angiopathy with nephropathy, aneurysms and muscle cramps. 

Genetic testing 

There are many approaches to genetic testing for children or adolescents with kidney disease.  Genetic testing should be ordered by a provider with knowledge of genetic testing and access to genetic specialists.  Given one’s medical and family history, a healthcare provider may wish to order targeted testing which can identify a specific genetic change (variant), variants within one gene, or variants in a small number of genes.