RESUMEN
BACKGROUND: Currently, microalbuminuria is the gold standard for detection and prediction of diabetic nephropathy (DN). However, microalbuminuria appears once significant kidney damage has actually occurred. OBJECTIVES: We investigated the diagnostic role of urinary Cyclophilin-A (uCypA), uCypA/creatinine ratio (uCypA/Cr) and serum Cystatin-C (sCysC) as biomarkers for early detection of DN in children with type 1 diabetes mellitus (T1DM) of short duration (2-5 years) before microalbuminuria emerges. METHODS: uCypA, uCypA/Cr, and sCysC levels were assessed in three age- and sex-matched groups; microalbuminuric diabetic group (n = 31), normoalbuminuric diabetic group (n = 29), and control group (n = 30). Glomerular filtration rate was estimated (eGFR) based on both serum creatinine (eGFR-Cr) and sCysC (eGFR-CysC). RESULTS: Significantly higher sCysC and lower eGFR-CysC were detected in both diabetic groups compared to controls and in microalbuminuric compared to normoalbuminuric group. No detected significant difference in eGFR-Cr values across the studied groups. Both uCypA and uCypA/Cr were significantly elevated in microalbuminuric compared to both normoalbuminuric and control groups with no difference between normoalbuminuric and control groups. Prediction of microalbuminuria was conducted using sCysC with area under curve up to 0.980. Combined use of sCysC and uCypA had better diagnostic value than uCypA alone. CONCLUSION: sCysC is a promising early biomarker for DN in childhood T1DM before albuminuria detection. eGFR-CysC is superior to eGFR-Cr in evaluating renal status in childhood T1DM. uCypA and uCypA/Cr were useful tools in predicting microalbuminuria, although not regarded as diagnostic biomarkers for early-stage DN in T1DM children by the current study.
Asunto(s)
Ciclofilina A/orina , Cistatina C/sangre , Diabetes Mellitus Tipo 1/complicaciones , Nefropatías Diabéticas/diagnóstico , Adolescente , Biomarcadores/sangre , Biomarcadores/orina , Estudios de Casos y Controles , Niño , Preescolar , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/orina , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/orina , Femenino , Tasa de Filtración Glomerular , Humanos , Masculino , Valor Predictivo de las PruebasAsunto(s)
Enfermedad de la Arteria Coronaria/sangre , Ciclofilina A/sangre , Diabetes Mellitus Tipo 2/sangre , Metaloproteinasa 9 de la Matriz/sangre , Adulto , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Enfermedad de la Arteria Coronaria/diagnóstico , Estudios Transversales , Diabetes Mellitus Tipo 2/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Regulación hacia ArribaRESUMEN
This study investigated the developmental toxicity of carbendazim during the organogenesis period in mice. Mated CD-1 mice were administered carbendazim at dose levels 0, 150, 300, and 600 mg/kg/day by gavage. Body weights, weight gains, and feed consumption were significantly reduced in mice administered with 300 and 600 mg/kg/day. Carbendazim exposure increased maternal levels of cholesterol, triglyceride, glucose, protein, and creatinine; and reduced the levels of estradiol and progesterone in the 300- and 600-mg/kg/day groups. In addition, exposure to carbendazim significantly reduced the number of live fetuses and increased the number of dead and resorptions at the same dose levels. External, visceral, and skeleton malformations were observed in the 300- and 600-mg/kg/day. In conclusion, exposure of pregnant mice to carbendazim induced maternal and developmental toxicity at 300 and 600 mg/kg/day. 150 mg/kg/day carbendazim produced a very slight increase in postimplantation loss, which was within the range of historical controls, and no evidence of maternal toxicity.