RESUMO
Dent disease is a rare X-linked tubulopathy characterized by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis and/or nephrolithiasis, progressive renal failure, and variable manifestations of other proximal tubule dysfunctions. It often progresses over a few decades to chronic renal insufficiency, and therefore molecular characterization is important to allow appropriate genetic counseling. Two genetic subtypes have been described to date: Dent disease 1 is caused by mutations of the CLCN5 gene, coding for the chloride/proton exchanger ClC-5; and Dent disease 2 by mutations of the OCRL gene, coding for the inositol polyphosphate 5-phosphatase OCRL-1. Herein, we review previously reported mutations (n = 192) and their associated phenotype in 377 male patients with Dent disease 1 and describe phenotype and novel (n = 42) and recurrent mutations (n = 24) in a large cohort of 117 Dent disease 1 patients belonging to 90 families. The novel missense and in-frame mutations described were mapped onto a three-dimensional homology model of the ClC-5 protein. This analysis suggests that these mutations affect the dimerization process, helix stability, or transport. The phenotype of our cohort patients supports and extends the phenotype that has been reported in smaller studies.
Assuntos
Canais de Cloreto/genética , Doença de Dent/genética , Mutação , Animais , Canais de Cloreto/química , Canais de Cloreto/metabolismo , Estudos de Coortes , Doença de Dent/metabolismo , Estudos de Associação Genética , Humanos , Masculino , Camundongos , Camundongos Knockout , LinhagemRESUMO
Protein loads in normal subjects increase glomerular filtration rate (GFR), which implies a renal functional reserve (RFR). Patients who have suffered a loss in the number of nephrons may show normal values of GFR due to hyperfiltration of remnant nephrons, with subsequent loss of RFR. This could be an early sign of renal damage, and probably a contributory factor to renal damage progress. The objective of this study is to determine the RFR through technetium-99m diethylene-triamine-penta-acetic acid (99m Tc-DTPA) clearance in patients who have recovered from hemolytic uremic syndrome. Renal functional reserve was determined in 33 children from 2 to 16 years old, with normal values of proteinuria, serum creatinine and creatinine clearance after over a year of having suffered hemolitic uremic syndrome. For that purpose 99m Tc-DTPA clearance was determined in basal condition and following protein load. In 17 patients DTPA clearance increased 20% or more after protein load compared to basal condition, and they were considered to have normal RFR, a probably index of totally recovered renal function; in the remaining 16 patients the increases were lower than 20%, and were considered to have no RFR, condition that was postulated as a contributing factor to renal damage progress. There was not significant differences either in age or basal GFR between both groups. Being the test easier than inuline clearance and more accurate than creatinine clearance, it proves particularly useful for early diagnosis of patients that need special follow-up and treatment.
Assuntos
Síndrome Hemolítico-Urêmica/diagnóstico por imagem , Síndrome Hemolítico-Urêmica/fisiopatologia , Compostos Radiofarmacêuticos , Pentetato de Tecnécio Tc 99m , Adolescente , Criança , Pré-Escolar , Feminino , Síndrome Hemolítico-Urêmica/metabolismo , Humanos , Rim/fisiopatologia , Masculino , Cintilografia , Compostos Radiofarmacêuticos/metabolismo , Pentetato de Tecnécio Tc 99m/metabolismoRESUMO
Normalmente, la ingesta de carga proteica aumenta el filtradoglomerular, lo que implica reserva funcional renal. Cuando disminuye el número de nefronas pueden observarse filtrados glomerulares normales por hiperfiltración, lo que implica pérdida de reserva funcional, temprano indicador de daño renal y, probablemente, factor contribuyente a su progresión. Determinamos el filtrado glomerular mediante la curva de desaparición plasmática del ácido dietilen-triamino-pentaacético marcado con tecnecio-99m, en pacientes con proteinuria y depuración de creatinina normal, que padecieron síndrome urémico-hemolítico con antelación mayor de 1 año. En 33 niños, de 2-16 años de edad, se determinó la reserva funcional renal mediante filtrado glomerular basal y tras carga proteica. Considerando normal un aumento superior al 20 por ciento, 16 pacientes mostraron no tener reserva funcional renal. Esta prueba, por su seguridad y fácil realización, resulta particularmente útil en pacientes que necesitan especial control y tratamiento.
Assuntos
Humanos , Masculino , Adolescente , Feminino , Pré-Escolar , Criança , Síndrome Hemolítico-Urêmica , Inulina , Nefropatias , Ácido Pentético , Interpretação Estatística de DadosRESUMO
The acute effect of angiotensin-converting enzyme inhibition (ACEi) on proximal convoluted tubule (PCT) function is well documented. However, the effect of chronic treatment is less known. The aim of this work was to evaluate the effect of chronic ACEi on PCT acidification (J(HCO(3)(-))). Rats received enalapril (10 mg.kg(-1).day(-1), added to the drinking water) during 3 mo. Micropuncture experiments were performed to measure the effect of chronic ACEi on J(HCO(3)(-)). Nitric oxide (NO.) synthesis in kidney cortex homogenates was assessed by quantifying the conversion of [(14)C]-L-arginine to [(14)C]-L-citrulline. Western blot analysis was performed to determine the abundances of V-H(+)ATPase and NHE3 isoform of the Na(+)/H(+) exchanger in proximal brush-border membrane vesicles (BBMV). Enalapril treatment induced an approximately 50% increase in J(HCO(3)(-)). Luminal perfusion with ethyl-isopropyl amiloride (EIPA) 10(-4)M or bafilomycin 10(-6)M decreased J(HCO(3)(-)) by approximately 60% and approximately 30%, respectively, in both control and enalapril-treated rats. The effect of EIPA and bafilomycin on absolute J(HCO(3)(-)) was larger in enalapril-treated than in control rats. Acute inhibition of NO. synthesis with N(G)-nitro-L-arginine methyl ester abolished the enalapril-induced increase in J(HCO(3)(-)). Cortex homogenates from enalapril-treated rats displayed a 46% increase in nitric oxide synthase (NOS) activity compared with those from untreated animals. Enalapril treatment did not affect the abundances of NHE3 and V-H(+)ATPase in BBMV. Our results suggest that PCT acidification is increased during chronic ACEi probably due to an increase in NO. synthesis, which would stimulate Na(+)/H(+) exchange and electrogenic proton transport.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Túbulos Renais Proximais/metabolismo , Peptidil Dipeptidase A/efeitos dos fármacos , Animais , Arginina/metabolismo , Citrulina/metabolismo , Enalapril/farmacologia , Túbulos Renais Proximais/efeitos dos fármacos , Masculino , Óxido Nítrico/metabolismo , Oxirredução , Peptidil Dipeptidase A/metabolismo , Ratos , Ratos Wistar , Trocador 3 de Sódio-Hidrogênio , Trocadores de Sódio-Hidrogênio/metabolismo , ATPases Vacuolares Próton-Translocadoras/metabolismoRESUMO
La bacteriuria asintomática no tratada podría considerarsecomo una forma de profilaxis natural.Objetivo. Estimar la incidencia de infección urinariaen niños con bacteriuria asintomática.Población, material y métodos. Evaluamos 54 pacientesmayores de 2 años, sin patologías nefrourológicasprevias, que presentaron uno o más episodiosde bacteriuria asintomática.Mediante un estudio analítico observacional, retrospectivo,analizamos la incidencia acumulada de infección urinaria, los gérmenes tipificados, el tiempo promedio de aparición de la infección urinaria y su asociación con el uso de antibióticos.Se constituyeron dos grupos: Grupo A (con tratamientoantibiótico), 35 pacientes y grupo B (sin tratamiento), 19 pacientes.Duración del protocolo: 24 meses.Resultados. Grupo A: la incidencia acumulada deinfección urinaria fue de 26/35 pacientes (74 por ciento) en un tiempo promedio de 2 meses y 24 días desde eltratamiento antibacteriano, de acuerdo con lo determinadoa partir de la prueba ordinal logarítmica(Log Rank) 10,9 (p< 0,05); riesgo relativo 2,82, IC95 por ciento(1,29 menos 6,14); riesgo atribuible a la exposición 64 por ciento, IC 95 por ciento (0,22 menos 0,83) y número necesario para dañar, 2 pacientes.Un total de 18/26 pacientes cultivaron gérmenes enlas infecciones urinarias distintos a los identificadosen las bacteriurias asintomáticas.Grupo B: Incidencia acumulada: 5/19 pacientes(26 por ciento) en un tiempo promedio de 5 meses y 12 díasdesde la detección de la bacteriuria asintomática y4 de estos niños con gérmenes distintos en lasinfecciones urinarias.Conclusiones. El uso de antibióticos en pacientescon bacteriuria asintomática predispuso a la apariciónde infecciones urinarias con nuevas cepasbacterianas
Assuntos
Humanos , Pré-Escolar , Criança , Antibioticoprofilaxia , Bacteriúria , Infecções Bacterianas/urina , Estudos Epidemiológicos , Estudos RetrospectivosRESUMO
INTRODUCTION: Glomerular filtration rate (GFR) is the most widely used indicator of kidney function in patients with renal disease, although it does not invariably reflect functional status after renal injury. The concept of renal functional reserve (RFR) as the ability of the kidney to increase GFR following a protein load was introduced in the 1980s. In this study we evaluated the RFR test in 26 children who had developed hemolytic-uremic syndrome (HUS) at least 2 years before the first evaluation, then 8 years later. At the beginning of the study they had no signs of proteinuria, hypertension or renal insufficiency. RFR was also evaluated in 15 healthy control children. METHODS: Proteinuria and creatinine in serum and urine were tested. Functional reserve index (FRI) was defined in order to evaluate RFR. Patients with FRI level >1.36 were considered as responders (R) and with FRI <1.36 as non-responders (NR). RESULTS: R and NR groups failed to show any significant differences when basal creatinine clearance (C(Cr)) was evaluated. The NR group presented a significant low initial FRI that persisted unchanged at the end of the study. These patients developed proteinuria and a renal protector treatment with protein restriction was indicated. Although the proteinuria diminished, it remained within pathological range. The lack of RFR response in the NR group was significantly related to the presence of oliguria lasting longer than 8 days during the acute phase of disease. CONCLUSIONS: Those patients with a previous history of HUS with normal basal C(Cr) should be evaluated by the RFR test to detect those at risk of developing glomerular hyperfiltration.