Pediatric Nephrology Unit, Department of Pediatrics, Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Enéas Carvalho de Aguiar, 647, São Paulo, CEP: 05403-000, SP, Brazil.
Department of Pediatrics, Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Pediatr Nephrol. 2019 Jun;34(6):1117-1128. doi: 10.1007/s00467-019-4195-4. Epub 2019 Jan 29.
Diagnosis of renal function impairment and deterioration in congenital urinary tract obstruction (UTO) continues to be extremely challenging. Use of renal biomarkers in this setting may favor early renal injury detection, allowing for a reliable choice of optimal therapeutic options and prevention or minimization of definitive renal damage.
This longitudinal, prospective study analyzed the first-year profile of two serum renal biomarkers: creatinine (sCr) and cystatin C (sCyC); and six urinary renal biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), transforming growth factor beta-1 (TGF-β1), retinol-binding protein (RBP), cystatin C (uCyC), and microalbuminuria (μALB) in a cohort of 37 infants with UTO divided into three subgroups: 14/37 with unilateral hydro(uretero)nephrosis, 13/37 with bilateral hydro(uretero)nephrosis, and 10/37 patients with lower urinary tract obstruction (LUTO), compared with 24 healthy infants matched by gestational age and birth weight.
All urine biomarkers showed significantly higher values at the first month of life (p ≤ 0.009), while NGAL (p = 0.005), TGF-ß1 (p < 0.001), and μALB (p < 0.001) were high since birth compared to controls. Best single biomarker performances were RBP in bilateral hydronephrosis and LUTO subgroups and KIM-1 in unilateral hydronephrosis subgroup. Best biomarker combination results for all subgroups were obtained by matching RBP with TGF-ß1 or KIM-1 and NGAL with CyC ([AUC] ≤ 0.934; sensitivity ≤ 92.4%; specificity ≤ 92.8%).
RBP, NGAL, KIM-1, TGF-ß1, and CyC, alone and especially in combination, are relatively efficient in identifying surgically amenable congenital UTO and could be of practical use in indicating on-time surgery.
先天性尿路梗阻(UTO)患者肾功能损伤和恶化的诊断仍然极具挑战性。在这种情况下使用肾生物标志物可以更早地发现肾损伤,从而能够可靠地选择最佳治疗方案,并预防或最小化终末期肾损伤。
本纵向前瞻性研究分析了 37 例UTO 婴儿的前一年血清肾生物标志物肌酐(sCr)和胱抑素 C(sCyC),以及 6 种尿肾生物标志物中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、肾损伤分子-1(KIM-1)、转化生长因子-β1(TGF-β1)、视黄醇结合蛋白(RBP)、胱抑素 C(uCyC)和微量白蛋白尿(μALB)的特征。37 例UTO 患儿分为 3 组:单侧肾积水 14 例,双侧肾积水 13 例,下尿路梗阻(LUTO)10 例,与 24 例按胎龄和出生体重匹配的健康婴儿进行比较。
所有尿液生物标志物在生命的第一个月均显示出明显更高的值(p≤0.009),而 NGAL(p=0.005)、TGF-ß1(p<0.001)和μALB(p<0.001)出生时即高于对照组。RBP 在双侧肾积水和 LUTO 亚组,KIM-1 在单侧肾积水亚组中具有最佳的单一生物标志物性能。所有亚组中最佳生物标志物组合结果是将 RBP 与 TGF-ß1 或 KIM-1 以及 NGAL 与 CyC 匹配([AUC]≤0.934;敏感性≤92.4%;特异性≤92.8%)。
RBP、NGAL、KIM-1、TGF-ß1 和 CyC 单独使用,特别是联合使用,在识别可手术治疗的先天性 UTO 方面相对有效,可能对及时手术有实际意义。