Spironolactone reduces oxidative stress in living donor kidney transplantation: A randomized controlled trial
Por:
Morales-Buenrostro L.E., Ortega-Trejo J.A., Perez-Villalva, Rasalba, Marino, Lluvia A., Gonzalez-Bobadilla, Yvett, Juarez, Hilda, Zamora-Mejia, Flor M., Gonzalez, Norma, Espinoza, Ramon, Barrera-Chimal, Jonatan, Bobadilla, Norma A.
Publicada:
1 ene 2019
Resumen:
Mineralocorticoid receptor antagonism prevents acute kidney injury induced by ischemia-reperfusion in rodent and pig preclinical models. In a pilot study, we showed that spironolactone (25 mg) reduced oxidative stress after 5 days of kidney transplant (KT). In the present study, we investigated the effects of higher doses (50 and 100 mg) of spironolactone on kidney function, tubular injury markers, and oxidative stress in living donor KT recipients. We included KT recipients aged 18 yr or older who received immunosuppression therapy with IL-2 receptor antagonist, mycophenolate mofetil, corticosteroids, and tacrolimus with negative cross-match, and compatible blood group. Patients were randomized to receive placebo (n = 27), spironolactone (50 mg, n = 25), or spironolactone (100 mg, n = 25). Treatment was given from 3 days before and up to 5 days after KT. Serum creatinine, K+, urine neutrophil gelatinase-associated lipocalin-2, heat shock protein 72, and 8-hydroxy-2-deoxyguanosine levels were assessed. As expected, kidney function was improved after KT. Serum K+ remained in the normal range along the study. There was no significant effect of spironolactone on urinary neutrophil gelatinase-associated lipocalin-2 levels, whereas the increase in urinary heat shock protein 72 levels tended to be less intense in the 100 mg spironolactone-treated group (P = 0.054). In the placebo-treated group, urinary 8-hydroxylated-guanosine levels increased on days 3 and 5 after transplantation. This effect was prevented in patients that received spironolactone. In conclusion, spironolactone reduces the acute increase in urinary oxidative stress in living donor KT recipients. © 2019, the American Physiological Society.
Filiaciones:
Morales-Buenrostro L.E.:
Department of Nephrology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Ortega-Trejo J.A.:
Department of Nephrology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico
Perez-Villalva, Rasalba:
Department of Nephrology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Nephrol, Mexico City, DF, Mexico
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Mol Physiol Unit, Mexico City, DF, Mexico
Marino, Lluvia A.:
Department of Nephrology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Nephrol, Mexico City, DF, Mexico
Gonzalez-Bobadilla, Yvett:
Department of Nephrology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Nephrol, Mexico City, DF, Mexico
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Mol Physiol Unit, Mexico City, DF, Mexico
Juarez, Hilda:
Department of Nephrology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Nephrol, Mexico City, DF, Mexico
Zamora-Mejia, Flor M.:
Department of Nephrology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Nephrol, Mexico City, DF, Mexico
Gonzalez, Norma:
Department of Nephrology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Nephrol, Mexico City, DF, Mexico
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Mol Physiol Unit, Mexico City, DF, Mexico
Espinoza, Ramon:
Transplantation Unit, Centro Médico Nacional Siglo XXI, Mexico City, Mexico
Ctr Med Nacl Siglo XXI, Transplantat Unit, Mexico City, DF, Mexico
Barrera-Chimal, Jonatan:
Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico
Unidad de Medicina Traslacional, UNAM-Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Mol Physiol Unit, Mexico City, DF, Mexico
UNAM Inst Nacl Cardiol Ignacio Chavez, Unidad Med Traslac, Mexico City, DF, Mexico
Bobadilla, Norma A.:
Department of Nephrology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Nephrol, Mexico City, DF, Mexico
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Mol Physiol Unit, Mexico City, DF, Mexico
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