Hypoxia-inducible factor-1 alpha and nuclear factor erythroid 2-related factor 2 as biomarkers of renal scarring in children with congenital anomalies of the kidney and urinary tract: a prospective case-control study.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) represent a diverse group of structural malformations that can lead to renal fibrosis and chronic kidney disease in children. Although hypoxia-inducible factor-1 alpha (HIF-1α) and nuclear factor erythroid 2-related factor 2 (NRF2) have been suspected of fibrotic processes in kidney diseases, their roles in CAKUT-related renal fibrosis remain unclear. In this context, this study was carried out to investigate the relationships between serum levels of HIF-1α and NRF2 and renal elastography findings, i.e., shear wave velocity (SWV) in children with CAKUT-related renal scarring compared to healthy control children. METHODS: The population of this cross-sectional study consisted of all consecutive children aged between one month and 18 years who were diagnosed with CAKUT at a tertiary referral center in Sanliurfa, Turkey, between January 2023 and April 2024. The patient group consisted of 44 children in whom dimercaptosuccinic acid (DMSA) scan revealed CAKUT-related renal scarring, and the control group consisted of 44 healthy children matched with the patient group in terms of age and gender. RESULTS: Children with CAKUT had significantly higher serum HIF-1α (p < 0.001) and NRF2 levels (p < 0.001) compared to controls. SWV values were also markedly elevated in the CAKUT group (p < 0.001), reflecting increased renal stiffness. A weak but significant positive correlation was found between HIF-1α levels and SWV values in the CAKUT group (r = 0.314, p = 0.038). However, this correlation was not observed when children with unilateral kidney agenesis were excluded (p = 0.075). CONCLUSIONS: Elevated HIF-1α and NRF2 levels were found to be associated with renal scarring in children with CAKUT, highlighting their potential roles as biomarkers for renal fibrosis. The correlation between HIF-1α levels and SWV values suggests that HIF-1α may serve as a predictor of renal fibrosis.