ABSTRACT
BACKGROUND: Congenital Anomalies of the Kidney and the Urinary Tract (CAKUT) are defined as a heterogeneous group of anomalies that resulted from defects in kidney and urinary tract embryogenesis. CAKUT have a complex etiology. Genetic, epigenetic and environmental factors have been investigated in this context. Angiotensin II is a potent vasoconstrictor and exerts an important role in kidney embryogenesis. The angiotensin-converting enzyme (ACE) converts Angiotensin I into Angiotensin II (Ang II) and ACE gene has insertion/deletion (I/D) polymorphisms that have been evaluated in several nephropathies. This study aimed to evaluate whether the I/D polymorphisms of ACE gene and the circulating levels of Ang II are associated with any CAKUT phenotype or CAKUT in general. METHODS AND RESULTS: Our study was performed with 225 pediatric patients diagnosed with CAKUT and 210 age-and-sex matched healthy controls. ACE I/D alleles were analysed by real-time polymerase chain reaction (RT-PCR). The distribution of ACE I/D polymorphisms were compared between CAKUT patients and healthy controls, as well between ureteropelvic junction obstruction (UPJO), vesicoureteral reflux (VUR), multicystic dysplastic kidney (MCDK) phenotypes and control group. No statistical association was detected between ACE I/D polymorphism and CAKUT and UPJO, VUR, and MCDK phenotypes. In a subset of 80 CAKUT patients and 80 controls, plasma levels of Ang II were measured. No significant differences were found between CAKUT patients and controls, even in regard to comparisons of UPJO, VUR and MCDK with control group. CONCLUSION: Although CAKUT is a complex disease and the ACE gene may exert a role in kidney embryogenesis, CAKUT was not associated with any ACE I/D polymorphisms nor with differences in plasma levels of Ang II in this Brazilian pediatric population.
Subject(s)
Ureteral Obstruction , Urinary Tract , Vesico-Ureteral Reflux , Angiotensin II/genetics , Child , Humans , Kidney , Peptidyl-Dipeptidase A , Polymorphism, Genetic , Urinary Tract/abnormalities , Vesico-Ureteral Reflux/geneticsABSTRACT
ABSTRACT Introduction: Glomerular hyperfiltration may lead to proteinuria and chronic kidney disease in unilateral multicystic dysplastic kidney (MCDK). We aimed to investigate the urine neutrophil-gelatinase-associated lipocalin (NGAL), netrin-1, hepcidin, and C-C motif chemokine ligand-2 (MCP-1/CCL-2) levels in patients with MCDK. Methods: Thirty-two patients and 25 controls were included. The urine hepcidin, netrin-1, NGAL, and MCP-1/CCL-2 levels were determined by ELISA. Results: The patients had higher serum creatinine (Cr) levels, urine albumin, and netrin-1/Cr ratio with lower GFR. There were positive correlations between urine protein/Cr, MCP-1/CCL-2/Cr, and netrin-1 with NGAL (r = 0.397, p = 0.031; r = 0.437, p = 0.041, r = 0.323, p = 0.042, respectively). Urine netrin-1/Cr was positively correlated with MCP-1/CCL-2/Cr (r = 0.356, p = 0.045). There were positive associations between the presence of proteinuria and netrin-1/Cr, MCP-1/CCL-2/Cr, and NGAL/Cr [Odds ratio (OR): 1.423, p = 0.037, OR: 1.553, p = 0.033, OR: 2.112, p = 0.027, respectively)]. ROC curve analysis showed that netrin-1/Cr, MCP-1/CCL-2/Cr, and NGAL/Cr had high predictive values for determining proteinuria p = 0.027, p = 0.041, p = 0.035, respectively). Urine hepcidin/Cr was negatively correlated with tubular phosphorus reabsorption and was positively correlated with urine NGAL/Cr (r = -0.418, p = 0.019; r = 0.682, p = 0.000; respectively). Conclusions: MCP-1/CCL-2 may play a role in the development of proteinuria in MCDK. Netrin-1 may be a protective factor against proteinuria-induced renal injury. Urine hepcidin/Cr may reflect proximal tubule damage in MCDK. Urine NGAL/Cr may be a predictor of tubule damage by proteinuria.
Resumo Introdução: A hiperfiltração glomerular pode causar proteinúria e doença renal crônica no rim displásico multicístico unilateral (RDM). Nosso objetivo foi investigar os níveis de lipocalina associada à gelatinase neutrofílica na urina (NGAL), netrina-1, hepcidina e quimiocina C-C com ligante-2 (MCP-1/CCL-2) em pacientes com RDM. Métodos: Trinta e dois pacientes e 25 controles foram incluídos. Os níveis urinários de hepcidina, netrin-1, NGAL e MCP-1/CCL-2 foram determinados por ELISA. Resultados: Os pacientes apresentaram níveis séricos mais elevados de creatinina (Cr), albumina na urina e relação netrina-1/Cr com menor TFG. Houve correlação positiva entre proteína na urina/Cr, MCP-1/CCL-2/Cr e netrina-1 com NGAL (r = 0,397, p = 0,031; r = 0,437, p = 0,041, r = 0,323, p = 0,042, respectivamente). A netrina-1/Cr na urina foi correlacionada positivamente com MCP-1/CCL-2/Cr (r = 0,356, p = 0,045). Houve associações positivas entre a presença de proteinúria e netrina-1/Cr, MCP-1/CCL-2/Cr e NGAL/Cr [Odds ratio (OR): 1,423, p = 0,037, OR: 1,553, p = 0,033, OR: 2,112, p = 0,027, respectivamente) ]. A análise da curva ROC mostrou que netrina-1/Cr, MCP-1/CCL-2/Cr e NGAL/Cr apresentaram altos valores preditivos para determinar a proteinúria p = 0,027, p = 0,041, p = 0,035, respectivamente). A hepcidina/Cr na urina foi correlacionada negativamente com a reabsorção tubular de fósforo e positivamente com a NGAL/Cr na urina (r = -0,418, p = 0,019; r = 0,682, p = 0,000; respectivamente). Conclusões: MCP-1/CCL-2 pode ter participação no desenvolvimento de proteinúria no RDM. A Netrina-1 pode ser um fator protetor contra lesão renal induzida por proteinúria. Hepcidina/Cr na urina pode refletir danos em túbulos proximais no RDM. O valor de NGAL/Cr urinário pode ser um preditor de danos nos túbulos por proteinúria.
Subject(s)
Humans , Female , Multicystic Dysplastic Kidney/metabolism , Biomarkers , Proto-Oncogene Proteins , Chemokines , Creatinine , Hepcidins , Lipocalin-2 , Netrin-1 , LigandsABSTRACT
Introducción: La displasia renal multiquística (DRM) unilateral es una malformación frecuentemente encontrada en el ultrasonido obstétrico. En Colombia no existen publicaciones sobre las características clínicas y el comportamiento de esta enfermedad que permitan sugerir el tipo de estudios que se deben practicar en la fase inicial y en el seguimiento de estos niños. Objetivos: Describir las características clínicas de 40 pacientes con DRM unilateral con énfasis en la evaluación del riñón contralateral (RC) con respecto a sus funciones, tamaño y frecuencia de malformación urológicas asociadas. Metodología: Estudio descriptivo de pacientes menores de 18 años con diagnósticos pre o postnatales de DRM unilateral, atendidos en la consulta externa de nefrología pediátrica del Hospital Infantil Club Noel entre julio de 1997 y diciembre de 2007. Resultados: Se encontraron 40 pacientes. En ellos 88% el diagnóstico se hizo antes de nacer; 55% eran de sexo masculino, con una edad promedio al ingreso de 2 meses (rangos, 1 y 42 meses). En el RC se descubrió hidronefrosis (HN) en 2 casos (5%) y reflujo vesicoureteral (RVU) grados I yII en 3 casos (9%). El cálculo de la filtración glomerular fluctuó entre 81 ml/min/1.73 y 193 ml/min/1.73 (media, 105). Sólo uno de los 38 renogramas fue anormal e informó la presencia de una cicatriz renal. En el control ecográfico de 31 pacientes los quistes desaparecieron en 13 y persistían en 18, con una media de 60 meses (rango, 24 y 132 meses). El tiempo de seguimiento promedio fue 60 meses con un rango entre 15 y 132 meses. Conclusiones: En este grupo de pacientes se encontró buen pronóstico del RC: ninguno presentó disminución de la filtración glomerular y la frecuencia de malformaciones urológicas como la HN y el RVU fue muy baja. El ultrasonido renal (UR) es indispensable en la evaluación inicial y seguimiento de los casos.
Introduction: The multicystic dysplastic kidney (MDK) is a frequent malformation discovered in obstetrical ultrasound. In Colombia, there are no publications on clinical characteristics and follow up studies suggesting initial evaluation and follow up in these children. Objectives: To describe the clinical characteristics of 40 patients with unilateral MDK, with emphasis in the evaluation of the contra-lateral kidney (CK) regarding function, size, and associated urological malformations. Methodology: A review of cases of patients under 18 years of age with prenatal or postnatal diagnosis of unilateral MDK that attended the Pediatric Nephrology outpatient clinic at Hospital Infantil Club Noel in the city of Cali from July 1997 to December 2007. Results: A total of 40 patients were found. In 88% of these, diagnosis of unilateral MDK was done prenatally; of these, 55% were males with a mean age of 2 months of age (range 1 to 42 months). Evaluation of contra-lateral kidney showed: hydronephrosis (HN) in 2 cases (5%), vesicouretheral reflux (VUR) grades I and II in 3 cases (9%). Glomerular filtration fluctuated between 81 ml/min/1.73 and 193 ml/min/1.73 (mean 105). Radioisotope renography was performed in 38 patients and only one patient was reported with renal scar. Follow up with renal ultrasound revealed that renal cysts disappeared in 13 patients and persisted in 18 with a media of 60 months (range 15 to 132 months). Conclusions: In this group of patients, a good prognosis of the CK was found: none presented decline of the glomerular filtration rate and frequency of urological malformations as HN and VUR was very low.