Geraud Nicolas, Casemayou Audrey, Alves Melinda, Breuil Benjamin, Tkaczyk Marcin, Stańczyk Małgorzata, Szaflik Krzysztof, Talar Tomasz, Decramer Stéphane, Klein Julie, Schanstra Joost P, Meyer Bénédicte Buffin
National Institute of Health and Medical Research (INSERM), UMR 1297, Institute of Metabolic and Cardiovascular Disease, Toulouse, France.
University Paul Sabatier, Toulouse III, Toulouse, France.
Pediatr Nephrol. 2025 Apr;40(4):1023-1032. doi: 10.1007/s00467-024-06608-x. Epub 2024 Nov 30.
There are proposed roles for inflammation in the development of congenital obstructive uropathy in the setting of posterior urethral valves (PUV). However, the value of inflammatory proteins as predictive markers of postnatal kidney function, key in the management of fetuses with PUV, has not been explored. We screened fetal urine of fetuses with PUV with a panel of inflammatory proteins to determine their predictive value of postnatal kidney function.
Twenty-five different chemokines and cytokines were measured using a multiplex immunoassay in fetal urine of 79 PUV patients from retrospective cohorts, separated in discovery (n = 52) and validation (n = 27). The candidate markers were also quantified in amniotic fluid samples obtained from 16 PUV and 25 other congenital anomalies of the kidney and the urinary tract pregnancies. The performance of validated candidate inflammatory proteins was compared to the previously published 12PUV fetal urine peptide signature.
Fetal urine chemokines CCL2 (MCP-1), CXCL9 (MIG), and CCL4 (MIP-1β) were identified as predictive of postnatal kidney failure in fetuses with PUV from the discovery cohort. Their predictive potential was confirmed in the validation cohort (AUCs of 0.87, 0.81, and 0.86, respectively). The performance of these individual chemokines was lower than the previously published 12PUV fetal urine peptide signature. However, the combination of the three chemokines performed similarly to 12PUV. In contrast, these three chemokines were not predictive of outcome in amniotic fluid.
We identified chemokines in fetal urine of PUV pregnancies that, after external validation, could serve as predictive biomarkers of postnatal outcome and contribute to improve prenatal PUV management.
炎症在伴有后尿道瓣膜（PUV）的先天性梗阻性肾病的发生发展中可能发挥作用。然而，炎症蛋白作为出生后肾功能预测标志物的价值尚未得到探索，而出生后肾功能对于PUV胎儿的管理至关重要。我们使用一组炎症蛋白对PUV胎儿的尿液进行筛查，以确定它们对出生后肾功能的预测价值。
采用多重免疫分析法检测了来自回顾性队列的79例PUV患者胎儿尿液中的25种不同趋化因子和细胞因子，分为发现队列（n = 52）和验证队列（n = 27）。还对从16例PUV以及25例其他先天性肾和尿路异常妊娠中获取的羊水样本中的候选标志物进行了定量分析。将经过验证的候选炎症蛋白的性能与先前发表的12PUV胎儿尿液肽谱进行比较。
发现队列中，胎儿尿液趋化因子CCL2（MCP-1）、CXCL9（MIG）和CCL4（MIP-1β）被确定为PUV胎儿出生后肾衰竭的预测指标。它们的预测潜力在验证队列中得到证实（AUC分别为0.87、0.81和0.86）。这些单个趋化因子的性能低于先前发表的12PUV胎儿尿液肽谱。然而，这三种趋化因子的组合表现与12PUV相似。相比之下，这三种趋化因子对羊水中的结局没有预测作用。
我们在PUV妊娠胎儿尿液中鉴定出趋化因子，经外部验证后，这些趋化因子可作为出生后结局的预测生物标志物，有助于改善产前PUV管理。
