Gençler Aylin, Çelik Hakim, Padalı Fatih, Demir Abit, Kafadar Safiye
Department of Pediatric Nephrology, Faculty of Medicine, Harran University, Şanlıurfa, Turkey.
Department of Medical Physiology, Faculty of Medicine, Harran University, Şanlıurfa, Turkey.
BMC Nephrol. 2025 Jun 4;26(1):277. doi: 10.1186/s12882-025-04193-1.
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.
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.
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).
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.
先天性肾脏和尿路畸形（CAKUT）是一组多样的结构畸形，可导致儿童肾纤维化和慢性肾脏病。尽管缺氧诱导因子-1α（HIF-1α）和核因子红细胞2相关因子2（NRF2）被怀疑与肾脏疾病的纤维化过程有关，但其在CAKUT相关肾纤维化中的作用仍不清楚。在此背景下，本研究旨在探讨与健康对照儿童相比，CAKUT相关肾瘢痕形成儿童血清HIF-1α和NRF2水平与肾脏弹性成像结果（即剪切波速度（SWV））之间的关系。
本横断面研究的对象为2023年1月至2024年4月在土耳其尚勒乌尔法的一家三级转诊中心被诊断为CAKUT的所有连续的1个月至18岁儿童。患者组由44名儿童组成，其中二巯基丁二酸（DMSA）扫描显示有CAKUT相关肾瘢痕形成，对照组由44名在年龄和性别方面与患者组匹配的健康儿童组成。
与对照组相比，CAKUT患儿的血清HIF-1α（p < 0.001）和NRF2水平（p < 0.001）显著更高。CAKUT组的SWV值也明显升高（p < 0.001），反映出肾脏硬度增加。在CAKUT组中，HIF-1α水平与SWV值之间存在微弱但显著的正相关（r = 0.314，p = 0.038）。然而，排除单侧肾缺如的儿童后，未观察到这种相关性（p = 0.075）。
发现HIF-1α和NRF2水平升高与CAKUT患儿的肾瘢痕形成有关，突出了它们作为肾纤维化生物标志物的潜在作用。HIF-1α水平与SWV值之间的相关性表明，HIF-1α可能作为肾纤维化的预测指标。
