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.