Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Más filtros











Base de datos
Intervalo de año de publicación
1.
Kidney Int ; 94(3): 514-523, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30146013

RESUMEN

Pseudohypoaldosteronism type II (PHAII) is a genetic disease characterized by association of hyperkalemia, hyperchloremic metabolic acidosis, hypertension, low renin, and high sensitivity to thiazide diuretics. It is caused by mutations in the WNK1, WNK4, KLHL3 or CUL3 gene. There is strong evidence that excessive sodium chloride reabsorption by the sodium chloride cotransporter NCC in the distal convoluted tubule is involved. WNK4 is expressed not only in distal convoluted tubule cells but also in ß-intercalated cells of the cortical collecting duct. These latter cells exchange intracellular bicarbonate for external chloride through pendrin, and therefore, account for renal base excretion. However, these cells can also mediate thiazide-sensitive sodium chloride absorption when the pendrin-dependent apical chloride influx is coupled to apical sodium influx by the sodium-driven chloride/bicarbonate exchanger. Here we determine whether this system is involved in the pathogenesis of PHAII. Renal pendrin activity was markedly increased in a mouse model carrying a WNK4 missense mutation (Q562E) previously identified in patients with PHAII. The upregulation of pendrin led to an increase in thiazide-sensitive sodium chloride absorption by the cortical collecting duct, and it caused metabolic acidosis. The function of apical potassium channels was altered in this model, and hyperkalemia was fully corrected by pendrin genetic ablation. Thus, we demonstrate an important contribution of pendrin in renal regulation of sodium chloride, potassium and acid-base homeostasis and in the pathophysiology of PHAII. Furthermore, we identify renal distal bicarbonate secretion as a novel mechanism of renal tubular acidosis.


Asunto(s)
Acidosis Tubular Renal/fisiopatología , Túbulos Renales Colectores/fisiopatología , Proteínas Serina-Treonina Quinasas/genética , Seudohipoaldosteronismo/complicaciones , Transportadores de Sulfato/metabolismo , Acidosis Tubular Renal/sangre , Acidosis Tubular Renal/etiología , Animales , Modelos Animales de Enfermedad , Técnicas de Inactivación de Genes , Humanos , Túbulos Renales Colectores/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Mutación Missense , Potasio/sangre , Potasio/metabolismo , Seudohipoaldosteronismo/genética , Seudohipoaldosteronismo/fisiopatología , Eliminación Renal , Cloruro de Sodio/metabolismo , Simportadores de Sodio-Bicarbonato/metabolismo , Transportadores de Sulfato/genética , Regulación hacia Arriba
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA