Rubén Barba-Navarro1, Mirell Tapia-Silva1, Carlos Garza-Garcia1, Salvador López-Giacoman1, Ipsae Melgoza-Toral1, Armando Vázquez-Rangel1, Silvana Bazúa-Valenti2, Norma Bobadilla2, Michael Wasung de Lay1, Francisco Baranda1, Lakhmir S Chawla3, Gerardo Gamba4, Magdalena Madero5. 1. Departamento de Nefrología, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico. 2. Departamento de Nefrología y Metabolismo Mineral, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico. 3. Division of Intensive Care Medicine and Nephrology, Department of Medicine, Veterans Affairs Medical Center, Washington, DC. 4. Departamento de Nefrología y Metabolismo Mineral, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico. Electronic address: gamba@biomedicas.unam.mx. 5. Departamento de Nefrología, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico. Electronic address: madero.magdalena@gmail.com.
Abstract
BACKGROUND:Cardiac surgery-related acute kidney injury (AKI) is a common postoperative complication that greatly increases morbidity and mortality. There are currently no effective interventions to prevent AKI associated with cardiac surgery. Experimental data have shown that administration of the mineralocorticoid receptor blocker spironolactone prevents renal injury induced by ischemia-reperfusion in rats. The objective of this study was to test whether short-term perioperative administration of oral spironolactone could reduce the incidence of AKI in cardiac surgical patients. STUDY DESIGN: Randomized, double-blinded, placebo-controlled trial. SETTING & PARTICIPANTS: Data were collected from April 2014 through July 2015 at the National Heart Institute in Mexico. 233 patients were included; 115 and 118 receivedspironolactone or placebo, respectively. INTERVENTION: Spironolactone or placebo once at a dose of 100mg 12 to 24 hours before surgery and subsequently 3 further doses of 25mg in postoperative days 0, 1, and 2 were administered. OUTCOMES: Patients were followed up for 7 days or until discharge from the intensive care unit (ICU). The primary end point was AKI incidence defined by KDIGO criteria. Secondary end points included requirement of renal replacement therapy, ICU length of stay, and ICU mortality. Data were analyzed according to the intention-to-treat principle. RESULTS: Mean age was 53.2±15 years, mean serum creatinine level was 0.9±0.2mg/dL, median Thakar score for estimation of AKI risk was 2 (IQR, 1-3), and 25% had diabetes. The incidence of AKI was higher for the spironolactone group (43% vs 29%; P=0.02). No significant differences were found for secondary end points. LIMITATIONS: Single center, AKI was mostly driven by AKI stage 1, planned sample size was not achieved, and there was no renin-angiotensin-aldosterone system washout period. CONCLUSIONS: Our trial demonstrated that spironolactone was not protective for AKI associated with cardiac surgery and there may be a trend toward risk.
RCT Entities:
BACKGROUND: Cardiac surgery-related acute kidney injury (AKI) is a common postoperative complication that greatly increases morbidity and mortality. There are currently no effective interventions to prevent AKI associated with cardiac surgery. Experimental data have shown that administration of the mineralocorticoid receptor blocker spironolactone prevents renal injury induced by ischemia-reperfusion in rats. The objective of this study was to test whether short-term perioperative administration of oral spironolactone could reduce the incidence of AKI in cardiac surgical patients. STUDY DESIGN: Randomized, double-blinded, placebo-controlled trial. SETTING & PARTICIPANTS: Data were collected from April 2014 through July 2015 at the National Heart Institute in Mexico. 233 patients were included; 115 and 118 received spironolactone or placebo, respectively. INTERVENTION: Spironolactone or placebo once at a dose of 100mg 12 to 24 hours before surgery and subsequently 3 further doses of 25mg in postoperative days 0, 1, and 2 were administered. OUTCOMES: Patients were followed up for 7 days or until discharge from the intensive care unit (ICU). The primary end point was AKI incidence defined by KDIGO criteria. Secondary end points included requirement of renal replacement therapy, ICU length of stay, and ICU mortality. Data were analyzed according to the intention-to-treat principle. RESULTS: Mean age was 53.2±15 years, mean serum creatinine level was 0.9±0.2mg/dL, median Thakar score for estimation of AKI risk was 2 (IQR, 1-3), and 25% had diabetes. The incidence of AKI was higher for the spironolactone group (43% vs 29%; P=0.02). No significant differences were found for secondary end points. LIMITATIONS: Single center, AKI was mostly driven by AKI stage 1, planned sample size was not achieved, and there was no renin-angiotensin-aldosterone system washout period. CONCLUSIONS: Our trial demonstrated that spironolactone was not protective for AKI associated with cardiac surgery and there may be a trend toward risk.
Authors: Alhasan Mujtaba; Mohammed A Taher; Mazin A Hazza; Hassan M Al-Rubaye; Asaad H Kata; Hamid AbdulWahab; AbdulAmeer AbdulBari; Hayder K AlRubay Journal: Cardiol Ther Date: 2018-05-21
Authors: Oliver K Jawitz; Amanda S Stebbins; Vignesh Raman; Brooke Alhanti; Sean van Diepen; Matthias Heringlake; Stephen Fremes; Richard Whitlock; Steven R Meyer; Rajendra H Mehta; Mark Stafford-Smith; Shaun G Goodman; John H Alexander; Renato D Lopes Journal: Am Heart J Date: 2020-10-28 Impact factor: 4.749