Increased phosphorylation of the renal Na+-Cl- cotransporter in male kidney transplant recipient patients with hypertension: A prospective cohort
Por:
Rojas-Vega L., Jiménez-Vega A.R., Bazúa-Valenti S., Arroyo-Garza I., Jiménez J.V., Gómez-Ocádiz R., Carrillo-Pérez D.L., Moreno E., Morales-Buenrostro L.E., Alberú J., Gamba G.
Publicada:
15 nov 2015
Resumen:
Evidence in rodents suggests that tacrolimus-induced posttransplant hypertension is due to upregulation of the thiazide-sensitive Na+-Cl- cotransporter NCC. Here, we analyzed whether a similar mechanism is involved in posttransplant hypertension in humans. From January 2013 to June 2014, all adult kidney transplant recipients receiving a kidney allograft were enrolled in a prospective cohort study. All patients received tacrolimus as part of the immunosuppressive therapy. Six months after surgery, we assessed general clinical and laboratory variables, tacrolimus trough blood levels, and ambulatory 24-h blood pressure monitoring. Urinary exosomes were extracted to perform Western blot analysis using total and phospho-NCC antibodies. A total of 52 patients, including 17 women and 35 men, were followed. At 6 mo after transplantation, of the 35 men, 17 developed hypertension and 18 remained normotensive, while high blood pressure was observed in only 3 of 17 women. The hypertensive patients were significantly older than the normotensive group; however, there were no significant differences in body weight, history of acute rejection, renal function, and tacrolimus trough levels. In urinary exosomes, hypertensive patients showed higher NCC expression (1.7 ± 0.19) than normotensive (1 ± 0.13) (P ± 0.0096). Also, NCC phosphorylation levels were significantly higher in the hypertensive patients (1.57 ± 0.16 vs. 1 ± 0.07; P ± 0.0049). Our data show that there is a positive correlation between NCC expression/phosphorylation in urinary exosomes and the development of hypertension in posttransplant male patients treated with tacrolimus. Our results are consistent with the hypothesis that NCC activation plays a major role in tacrolimus-induced hypertension. © 2015 the American Physiological Society.
Filiaciones:
Rojas-Vega L.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Mol Physiol Unit, Mexico City 04510, DF, Mexico
Jiménez-Vega A.R.:
Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Bazúa-Valenti S.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Mol Physiol Unit, Mexico City 04510, DF, Mexico
Arroyo-Garza I.:
Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Jiménez J.V.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Mol Physiol Unit, Mexico City 04510, DF, Mexico
Gómez-Ocádiz R.:
Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Carrillo-Pérez D.L.:
Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Moreno E.:
Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Morales-Buenrostro L.E.:
Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Alberú J.:
Department of Transplantation, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Gamba G.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Mol Physiol Unit, Mexico City 04510, DF, Mexico
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