Monogenic alterations cause a variety of paediatric kidney diseases; however, insights into their association with clinical outcomes are limited. New analyses of three cohorts demonstrate that monogenic kidney disorders are associated with an increased risk of kidney failure. “These data suggest that recognition of genetic kidney disorders will be important for clinical evaluation, understanding prognosis, and counselling for patients,” say the researchers.

Mark Elliott and colleagues evaluated associations between diagnostic genetic analysis and clinical outcomes in three cohorts: the prospective Cure Glomerulonephropathy Network (CureGN) and two retrospective cohorts from Columbia University including 5,727 adults and children with kidney disease who underwent whole-genome or exome sequencing. Across all three cohorts, individuals with monogenic kidney disorders experienced an increased risk of kidney failure compared to those without (CureGN: HR 2.44, P = 2.42 × 10–3; Columbia-GN: HR 1.84, P = 0.033; Columbia-CKD: HR 1.59, P = 2.06 × 10–8). Individuals with monogenic kidney disorders also had a higher rate of decline in estimated glomerular filtration rate (eGFR) and were less likely to achieve complete remission. In two of the cohorts (Columbia-GN and Columbia-CKD), patients with high-risk APOL1 genotypes also had an increased risk of kidney failure, whereas patients with high-risk APOL1 genotypes in the CureGN cohort demonstrated a higher rate of eGFR decline. The researchers say their findings should motivate the search for more effective therapies for genetic kidney disorders.