Spironolactone on Acute Kidney Injury in Critically Ill Patients

Summary

This study was designed to evaluate the effect of spironolactone administration in the incidence and severity of AKI in patients critically ill with invasive mechanical ventilation (IMV) in the critical care unit. Patients in critical care unit (CCU) are the most at risk of developing AKI. In most cases a mechanism of ischemia/reperfusion has a central role in the development of AKI. Aldosterone has traditionally been recognized as a mediator that maintains water and sodium homeostasis. Nevertheless, there are enough evidence in humans and experimental models that aldosterone might mediate detrimental effects on renal function and structure in pathophysiological conditions. Indeed, several experimental studies from our laboratory have shown that mineralocorticoid receptor blockade protects the kidney against ischemia/reperfusion injury. The aim of this study is to know: o If mineralocorticoid receptor blockade may reduce the incidence and severity of AKI in critically patients with IMV in CCU. You may be able to enter in this study if: * You are at least 18 years old. * You are male or female * You are with IMV. * You are in CCU. * Your serum K is less than 4.5 mEq/L * Your BP is \>90/70 mmHg You cannot enter this study if: * You have CKD * You have AKI This study will recruit 90 patients from Instituto Nacional de Ciencias Médicas Salvador Zubiran in México City. The study will begin in April 2017. The patients will be randomized to one of 2 groups of treatment (Spironolactone 25 mg or placebo). All treatments looks identical (1 capsule), will be administered through the nasogastric tube. Neither the patients nor their doctors will be able to know or decide which group you are in. You will receive the medication during the first five days of stay in the critical care unit. As part of this trial, the doctors will ask your permission to get a sample urine during this days. They will use the samples to do tests in the laboratory (different to routine tests) that may help them to compare renal function and biomarkers of renal injury. Your participation will end 10 days after your entry into the critical care unit. The most common side effect of spironolactone is hyperkalemia.

Timeline

Start

2017-08-01

Primary completion

2019-12-31

Completion

2019-12-31

Publications

• Background Kuiper JW, Groeneveld AB, Slutsky AS, Plotz FB. Mechanical ventilation and acute renal failure. Crit Care Med. 2005 Jun;33(6):1408-15. doi: 10.1097/01.ccm.0000165808.30416.ef.
• Background Martensson J, Martling CR, Bell M. Novel biomarkers of acute kidney injury and failure: clinical applicability. Br J Anaesth. 2012 Dec;109(6):843-50. doi: 10.1093/bja/aes357. Epub 2012 Oct 9.
• Background Han WK, Bailly V, Abichandani R, Thadhani R, Bonventre JV. Kidney Injury Molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury. Kidney Int. 2002 Jul;62(1):237-44. doi: 10.1046/j.1523-1755.2002.00433.x.
• Background Liangos O, Perianayagam MC, Vaidya VS, Han WK, Wald R, Tighiouart H, MacKinnon RW, Li L, Balakrishnan VS, Pereira BJ, Bonventre JV, Jaber BL. Urinary N-acetyl-beta-(D)-glucosaminidase activity and kidney injury molecule-1 level are associated with adverse outcomes in acute renal failure. J Am Soc Nephrol. 2007 Mar;18(3):904-12. doi: 10.1681/ASN.2006030221. Epub 2007 Jan 31.
• Background Briet M, Schiffrin EL. Aldosterone: effects on the kidney and cardiovascular system. Nat Rev Nephrol. 2010 May;6(5):261-73. doi: 10.1038/nrneph.2010.30. Epub 2010 Mar 16.
• Background Del Vecchio L, Procaccio M, Vigano S, Cusi D. Mechanisms of disease: The role of aldosterone in kidney damage and clinical benefits of its blockade. Nat Clin Pract Nephrol. 2007 Jan;3(1):42-9. doi: 10.1038/ncpneph0362.
• Background Greene EL, Kren S, Hostetter TH. Role of aldosterone in the remnant kidney model in the rat. J Clin Invest. 1996 Aug 15;98(4):1063-8. doi: 10.1172/JCI118867.
• Background Rocha R, Stier CT Jr, Kifor I, Ochoa-Maya MR, Rennke HG, Williams GH, Adler GK. Aldosterone: a mediator of myocardial necrosis and renal arteriopathy. Endocrinology. 2000 Oct;141(10):3871-8. doi: 10.1210/endo.141.10.7711.
• Results Nisula S, Kaukonen KM, Vaara ST, Korhonen AM, Poukkanen M, Karlsson S, Haapio M, Inkinen O, Parviainen I, Suojaranta-Ylinen R, Laurila JJ, Tenhunen J, Reinikainen M, Ala-Kokko T, Ruokonen E, Kuitunen A, Pettila V; FINNAKI Study Group. Incidence, risk factors and 90-day mortality of patients with acute kidney injury in Finnish intensive care units: the FINNAKI study. Intensive Care Med. 2013 Mar;39(3):420-8. doi: 10.1007/s00134-012-2796-5. Epub 2013 Jan 5.
• Results Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Ronco C; Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005 Aug 17;294(7):813-8. doi: 10.1001/jama.294.7.813.
• Results de Mendonca A, Vincent JL, Suter PM, Moreno R, Dearden NM, Antonelli M, Takala J, Sprung C, Cantraine F. Acute renal failure in the ICU: risk factors and outcome evaluated by the SOFA score. Intensive Care Med. 2000 Jul;26(7):915-21. doi: 10.1007/s001340051281.
• Results Gallagher M, Cass A, Bellomo R, Finfer S, Gattas D, Lee J, Lo S, McGuinness S, Myburgh J, Parke R, Rajbhandari D; POST-RENAL Study Investigators and the ANZICS Clinical Trials Group. Long-term survival and dialysis dependency following acute kidney injury in intensive care: extended follow-up of a randomized controlled trial. PLoS Med. 2014 Feb 11;11(2):e1001601. doi: 10.1371/journal.pmed.1001601. eCollection 2014 Feb.
• Results Barrera-Chimal J, Perez-Villalva R, Cortes-Gonzalez C, Ojeda-Cervantes M, Gamba G, Morales-Buenrostro LE, Bobadilla NA. Hsp72 is an early and sensitive biomarker to detect acute kidney injury. EMBO Mol Med. 2011 Jan;3(1):5-20. doi: 10.1002/emmm.201000105. Epub 2010 Dec 14.
• Results Morales-Buenrostro LE, Salas-Nolasco OI, Barrera-Chimal J, Casas-Aparicio G, Irizar-Santana S, Perez-Villalva R, Bobadilla NA. Hsp72 is a novel biomarker to predict acute kidney injury in critically ill patients. PLoS One. 2014 Oct 14;9(10):e109407. doi: 10.1371/journal.pone.0109407. eCollection 2014.
• Results Pretorius M, Murray KT, Yu C, Byrne JG, Billings FT 4th, Petracek MR, Greelish JP, Hoff SJ, Ball SK, Mishra V, Body SC, Brown NJ. Angiotensin-converting enzyme inhibition or mineralocorticoid receptor blockade do not affect prevalence of atrial fibrillation in patients undergoing cardiac surgery. Crit Care Med. 2012 Oct;40(10):2805-12. doi: 10.1097/CCM.0b013e31825b8be2.
• Results Trachtman H, Weiser AC, Valderrama E, Morgado M, Palmer LS. Prevention of renal fibrosis by spironolactone in mice with complete unilateral ureteral obstruction. J Urol. 2004 Oct;172(4 Pt 2):1590-4. doi: 10.1097/01.ju.0000140445.82949.54.

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