Kidney injury risk in congenital solitary functioning kidney: the role of nephron mass assessed by serum uromodulin and the rs4293393 T > C polymorphism

Objective: We hypothesized that serum uromodulin levels (sUMOD) and the uromodulin rs4293393 T > C polymorphism could aid in risk stratification for kidney injury (KI) in patients with a congenital solitary functioning kidney (CSFK), serving as markers of nephron mass. We tested this hypothesis in a cohort study of 56 CSFK patients followed from birth to adulthood. The rs4293393 polymorphism was genotyped using the TaqMan assay. Serum uromodulin was measured at last follow-up using ELISA. KI was defined by estimated glomerular filtration rate < 90 ml/min/1.73m2 and/or hypertension and/or proteinuria. Results: Over a mean follow-up of 21.1years(range:18-33), 15 patients (26.8%) developed KI. Genotypes were TT (62.5%) and TC (37.5%). Higher sUMOD levels in early adulthood were linked to kidney length(KL) > 2SDS in early-life and absence of the C allele. Lower sUMOD levels were associated with KI and its components. Kaplan-Meier analysis showed 100% KI-free survival at 33years in patients with early KL > 2SDS. Survival dropped to 62.4% in those without early KL > 2SDS and wild-type genotype, and to 0% by 26years in C allele carriers (p = 0.001). The hazard ratio for KI in C allele carriers was 5.1(95%confidence interval:1.6-16.2;p = 0.006). Therefore, early-life kidney ultrasound, combined with rs4293393 genotyping might improve risk stratification for KI in patients with CSFK.