Abstract
Background and objectives
Acute kidney injury (AKI) after cardiac bypass surgery (CABG) is common and carries a significant association with morbidity and mortality. Since minocycline therapy attenuates kidney injury in animal models of AKI, we tested its effects in patients undergoing CABG.
Design, setting, participants and measurements
This is a randomized, double-blinded, placebo-controlled, multi-center study. We screened high risk patients who were scheduled to undergo CABG in two medical centers between Jan 2008 and June 2011. 40 patients were randomized and 19 patients in each group completed the study. Minocycline prophylaxis was given twice daily, at least for four doses prior to CABG. Primary outcome was defined as AKI [0.3 mg/dl increase in creatinine (Cr)] within 5 days after surgery. Daily serum Cr for 5 days, various clinical and hemodynamic measures and length of stay were recorded.
Results
The two groups had similar baseline and intra-operative characteristics. The primary outcome occurred in 52.6 % of patients in the minocycline group as compared to 36.8 % of patients in the placebo group (p = 0.51). Peak Cr was 1.6 ± 0.7 vs. 1.5 ± 0.7 mg/dl (p = 0.45) in minocycline and placebo groups, respectively. Death at 30 days occurred in 0 vs. 10.5 % in the minocycline and placebo groups, respectively (p = 0.48). There were no differences in post-operative length of stay, and cardiovascular events between the two groups. There was a trend towards lower diastolic pulmonary artery pressure [16.8 ± 4.7 vs. 20.7 ± 6.6 mmHg (p = 0.059)] and central venous pressure [11.8 ± 4.3 vs. 14.6 ± 5.6 mmHg (p = 0.13)] in the minocycline group compared to placebo on the first day after surgery.
Conclusions
Minocycline did not protect against AKI post-CABG.
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References
Mehta RL (2005) Acute renal failure and cardiac surgery: marching in place or moving ahead? J Am Soc Nephrol 16(1):12–14
Chertow GM et al (1998) Independent association between acute renal failure and mortality following cardiac surgery. Am J Med 104(4):343–348
Fortescue EB, Bates DW, Chertow GM (2000) Predicting acute renal failure after coronary bypass surgery: cross-validation of two risk-stratification algorithms. Kidney Int 57(6):2594–2602
Slogoff S et al (1990) Role of perfusion pressure and flow in major organ dysfunction after cardiopulmonary bypass. Ann Thorac Surg 50(6):911–918
Thakar CV et al (2005) A clinical score to predict acute renal failure after cardiac surgery. J Am Soc Nephrol 16(1):162–168
Thakar CV et al (2003) ARF after open-heart surgery: influence of gender and race. Am J Kidney Dis 41(4):742–751
Tuttle KR et al (2003) Predictors of ARF after cardiac surgical procedures. Am J Kidney Dis 41(1):76–83
Chertow GM et al (1997) Preoperative renal risk stratification. Circulation 95(4):878–884
Abramov D et al (2003) The influence of cardiopulmonary bypass flow characteristics on the clinical outcome of 1820 coronary bypass patients. Can J Cardiol 19(3):237–243
Fischer UM et al (2002) Impact of cardiopulmonary bypass management on postcardiac surgery renal function. Perfusion 17(6):401–406
Rosner MH, Okusa MD (2006) Acute kidney injury associated with cardiac surgery. Clin J Am Soc Nephrol 1:19–32
Devarajan P (2006) Update on mechanisms of ischemic acute kidney injury. J Am Soc Nephrol 17(6):1503–1520
Molitoris BA (2003) Transitioning to therapy in ischemic acute renal failure. J Am Soc Nephrol 14(1):265–267
Molitoris BA, Sutton TA (2004) Endothelial injury and dysfunction: role in the extension phase of acute renal failure. Kidney Int 66(2):496–499
Okusa MD (2002) The inflammatory cascade in acute ischemic renal failure. Nephron 90(2):133–138
Sheridan AM, Bonventre JV (2000) Cell biology and molecular mechanisms of injury in ischemic acute renal failure. Curr Opin Nephrol Hypertens 9(4):427–434
Sutton TA, Fisher CJ, Molitoris BA (2002) Microvascular endothelial injury and dysfunction during ischemic acute renal failure. Kidney Int 62(5):1539–1549
Griffin MO et al (2010) Tetracyclines: a pleitropic family of compounds with promising therapeutic properties. Review of the literature. Am J Physiol Cell Physiol 299:C539–C548
Nieman GF, Zerler BR (2001) A role for the anti-inflammatory properties of tetracyclines in the prevention of acute lung injury. Curr Med Chem 8(3):317–325
Arvin KL et al (2002) Minocycline markedly protects the neonatal brain against hypoxic-ischemic injury. Ann Neurol 52(1):54–61
Cheung PY et al (2000) Matrix metalloproteinase-2 contributes to ischemia-reperfusion injury in the heart. Circulation 101(15):1833–1839
Sloan R et al (2012) Mitochondrial permeability transition in the diabetic heart: contributions of thiol redox state and mitochondrial calcium to augmented reperfusion injury. J Mol Cell Card 52:1009–1018
Tikka T et al (2001) Tetracycline derivatives and ceftriaxone, a cephalosporin antibiotic, protect neurons against apoptosis induced by ionizing radiation. J Neurochem 78(6):1409–1414
Power C et al (2003) Intracerebral hemorrhage induces macrophage activation and matrix metalloproteinases. Ann Neurol 53(6):731–742
Chen M et al (2000) Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease. Nat Med 6(7):797–801
Zhu S et al (2002) Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice. Nature 417(6884):74–78
Xia D et al (2011) Adminsitration of minocycline ameliorates damage in a renal ischemia/reperfusion injury model. Clin Invest Med 34(2):E55–E63
Du X et al (2012) Involvement of matrix metalloproteinase-2 in the development of renal interstitial fibrosis in mouse obstructive nephropathy. Lab Invest 92:1149–1160
Tao R et al (2010) Minocycline protects cardiac myocytes against simulated ischemia-reperfusion injury by inhibiting poly(ADP-ribose)polymerase-1. J Cardiovasc Pharmacol 56(6):659–668
Conflict of interest
This study was supported by a Norman Coplon Grant from Satellite Healthcare, and by a limited grant from Triax Pharmaceuticals (makers of generic form of minocycline).
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Golestaneh, L., Lindsey, K., Malhotra, P. et al. Acute kidney injury after cardiac surgery: is minocycline protective?. J Nephrol 28, 193–199 (2015). https://doi.org/10.1007/s40620-014-0152-2
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DOI: https://doi.org/10.1007/s40620-014-0152-2