RESUMEN
BACKGROUND AND OBJECTIVES: Obstructive nephropathy is a leading cause of CKD in children. The assessment of severity of renal impairment and the prediction of which children will progress to renal failure are, however, challenging. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This case-control study measured the urinary excretion of candidate biomarkers in 27 prevalent case-patients with posterior urethral valves (PUVs) and 20 age-matched controls, correlated their urinary concentration with GFR, and analyzed receiver-operating characteristic (ROC) curve and regression analyses to assess their performance as tests for low GFR. RESULTS: The median urinary protein-to-creatinine ratio was higher in children with PUV (45 g/mol; range, 5-361 g/mol) than in controls (7 g/mol; range, 3-43 g/mol) (P<0.01) and correlated inversely with renal function (r = -0.44; P<0.05). In whole urine, excretion of aquaporin-2 was significantly decreased, whereas that of TGFß and L1 cell adhesion molecule (L1CAM) was significantly increased. Whole-urine TGFß excretion correlated inversely with GFR (r = -0.53; P<0.05). As tests for low GFR, whole-urine TGFß, L1CAM, and urinary protein-to-creatinine ratio performed best, with areas under the ROC curves of 0.788, 0.795, and 0.814, respectively. By linear regression analysis, whole-urine TGFß, L1CAM, and urinary protein-to-creatinine ratio were associated with low GFR in the case-patients. CONCLUSIONS: Candidate biomarkers of obstructive nephropathy can be readily measured in whole urine and in urine exosomes. In boys with PUV, these biomarkers correlate with GFR.
Asunto(s)
Enfermedades Renales/orina , Riñón/fisiopatología , Molécula L1 de Adhesión de Célula Nerviosa/orina , Factor de Crecimiento Transformador beta/orina , Obstrucción Uretral/complicaciones , Adolescente , Antígenos CD/orina , Acuaporina 2/orina , Área Bajo la Curva , Biomarcadores/orina , Cadherinas/orina , Estudios de Casos y Controles , Niño , Preescolar , Creatinina/orina , Progresión de la Enfermedad , Exosomas/metabolismo , Estudios de Factibilidad , Tasa de Filtración Glomerular , Humanos , Lactante , Enfermedades Renales/diagnóstico , Enfermedades Renales/etiología , Enfermedades Renales/fisiopatología , Fallo Renal Crónico/etiología , Fallo Renal Crónico/orina , Modelos Lineales , Modelos Logísticos , Masculino , Valor Predictivo de las Pruebas , Proteinuria/etiología , Proteinuria/orina , Proteómica/métodos , Curva ROC , Canales Catiónicos TRPV/orina , Obstrucción Uretral/fisiopatología , Obstrucción Uretral/orina , Urinálisis , ATPasas de Translocación de Protón Vacuolares/orina , beta Catenina/orinaRESUMEN
The L1 cell adhesion molecule (CD171) is a multidomain membrane glycoprotein of the immunoglobulin superfamily. We evaluated its expression in human acute kidney injury and assessed its use as a tissue and urinary marker of acute tubular injury. Using immunohistochemical studies with antibodies to the extracellular or cytoplasmic domains, we compared L1 expression in normal kidneys in 24 biopsies taken from patients with acute tubular necrosis. L1 was found at the basolateral and the lateral membrane in all epithelial cells of the collecting duct in the normal kidney except for intercalated cells. In acute tubular necrosis, L1 lost its polarized distribution being found in both the basolateral and apical domains of the collecting duct. Further, it was induced in thick ascending limb and distal tubule cells. Apically expressed L1 found only when the cytoplasmic domain antibody was used in biopsy specimens of patients with acute tubular necrosis. The levels of urinary L1, normalized for creatinine, were significantly higher in all 24 patients with acute tubular necrosis compared to five patients with prerenal azotemia or to six patients with other causes of acute kidney injury. Our study shows that a soluble form of human L1 can be detected in the urine of patients with acute tubular necrosis and that this may be a marker of distal nephron injury.