Skip to main content

Plasma renalase as a biomarker of acute kidney injury after cardiac surgery

Abstract

Background

Renal ischemia/reperfusion injury is a major cause of acute renal failure. The lack of validated early biomarkers for predicting acute kidney injury (AKI) has hampered our ability to initiate potentially preventive and therapeutic measures in an opportune way. We tested the hypothesis that plasma renalase is an early biomarker for ischemic renal injury after cardiac surgery.

Patients and methods

We prospectively evaluated 40 adult patients who underwent cardiac surgery. Patients were divided into the AKI group and the non-AKI group on the basis of whether they developed postoperative AKI within 48 h after surgery. Plasma renalase levels were measured before surgery and 24 h after surgery. The primary outcome was AKI diagnosed using the Acute Kidney Injury Network criteria.

Results

Twenty-five (62.5%) patients developed AKI after surgery. Plasma renalase decreased significantly from a mean of 1.2±0.46 ng/ml at baseline to 0.9 ±0.42 ng/ml 24 h after cardiopulmonary bypass, with a mean %change of 27 ±14.8 in the AKI group. Univariate analysis showed a significant correlation between AKI and the following: %change in plasma renalase, cardiopulmonary bypass time, and aortic cross-clamp time. Receiver operating characteristic curve analysis revealed that for %change in plasma renalase concentrations at 24 h, the area under the curve was 0·9, sensitivity was 0.92, specificity was 0·87, and likelihood ratio was 7.07 for a cutoff value of 9% change.

Conclusion

Plasma renalase %change is more valid compared with renalase before or after procedure and neutrophil gelatinase-associated lipocalin in the prediction of AKI and represents a novel and highly predictive early biomarker for AKI after cardiac surgery.

References

  1. Conlon PJ, Stafford-Smith M, White WD, Newman MF, King S, Winn MP et al. Acute renal failure following cardiac surgery. Nephrol Dial Transplant 1999; 14:1158–1162.

    CAS  Article  Google Scholar 

  2. Kuitunen A, Vento A, Suojaranta-Ylinen R, Pettila V. Acute renal failure after cardiac surgery: evaluation of the RIFLE classification. Ann Thorac Surg 2006; 81:542–546.

    Article  Google Scholar 

  3. Chertow GM, Lazarus JM, Christiansen CL, Cook EF, Hammermeister KE, Grover F, et al. Preoperative renal risk stratification. Circulation 1997; 95:878–884.

    CAS  Article  Google Scholar 

  4. Wald R, Quinn RR, Luo J, Li P, Scales DC, Mamdani MM, et al. Chronic dialysis and death among survivors of acute kidney injury requiring dialysis. JAMA 2009; 302:1179–1185.

    CAS  Article  Google Scholar 

  5. Rosner MH, Okusa MD. Acute kidney injury associated with cardiac surgery. Clin J Am Soc Nephrol 2006; 1:19–32.

    Article  Google Scholar 

  6. Gaffney AM, Sladen RN. Acute kidney injury in cardiac surgery. Curr Opin Anaesthesiol 2015; 28:50–59.

    Article  Google Scholar 

  7. Wagener G, Gubitosa G, Wang S, Borregaard N, Kim M, Lee HT. Urinary neutrophil gelatinase-associated lipocalin and acute kidney injury after cardiac surgery. Am J Kidney Dis 2008; 52:425–433.

    CAS  Article  Google Scholar 

  8. Noguchi S, Kashihara Y, Ikegami Y, Morimoto K, Miyamoto M, Nakao K. Insulin-like growth factor-I ameliorates transient ischemia-induced acute renal failure in rats. J Pharmacol Exp Ther 1993; 267:919–926.

    CAS  PubMed  Google Scholar 

  9. Conger JD, Falk SA, Yuan BH, Schrier RW. Atrial natriuretic peptide and dopamine in a rat model of ischemic acute renal failure. Kidney Int 1989; 35:1126–1132.

    CAS  Article  Google Scholar 

  10. Mishra J, Mori K, Ma Q, Kelly C, Yang J, Mitsnefes M, et al. Amelioration of ischemic acute renal injury by neutrophil gelatinase-associated lipocalin. J Am Soc Nephrol 2004; 15:3073–3082.

    Article  Google Scholar 

  11. Bonventre JV, Weinberg JM. Recent advances in the pathophysiology of ischemic acute renal failure. J Am Soc Nephrol 2003; 14:2199–2210.

    Article  Google Scholar 

  12. De Geus HRH, Betjes MG, Bakker J. Biomarkers for the prediction of acute kidney injury: a narrative review on current status and future challenges. Clin Kidney J 2012; 5:102–108.

    Article  Google Scholar 

  13. Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 2005; 365:1231–1238.

    CAS  Article  Google Scholar 

  14. Parikh CR, Mishra J, Thiessen-Philbrook H, Dursun B, Ma Q, Kelly C, et al. Urinary IL-18 is an early predictive biomarker of acute kidney injury after cardiac surgery. Kidney Int 2006; 70:199–203.

    CAS  Article  Google Scholar 

  15. Portilla D, Dent C, Sugaya T, Nagothu KK, Kundi I, Moore P, et al. Liver fatty acid-binding protein as a biomarker of acute kidney injury after cardiac surgery. Kidney Int 2008; 73:465–472.

    CAS  Article  Google Scholar 

  16. Thurman JM, Parikh CR. Peeking into the black box: new biomarkers for acute kidney injury. Kidney Int 2008; 73:379–381.

    CAS  Article  Google Scholar 

  17. Wagener G, Jan M, Kim M, Mori K, Barasch JM, Sladen RN, et al. Association between increases in urinary neutrophil gelatinase-associated lipocalin and acute renal dysfunction after adult cardiac surgery. Anesthesiology 2006; 105:485–491.

    CAS  Article  Google Scholar 

  18. Koyner JL, Bennett MR, Worcester EM, Ma Q, Raman J, Jeevanandam V, et al. Urinary cystatin C as an early biomarker of acute kidney injury following adult cardiothoracic surgery. Kidney Int 2008; 74:1059–1069.

    CAS  Article  Google Scholar 

  19. Katagiri D, Doi K, Honda K, Negishi K, Fujita T, Hisagi M, et al. Combination of two urinary biomarkers predicts acute kidney injury after adult cardiac surgery. Ann Thorac Surg 2012; 93:577–583.

    Article  Google Scholar 

  20. Xu J, Li G, Wang P, Velazquez H, Yao X, Li Y, et al. Renalase is a novel, soluble monoamine oxidase that regulates cardiac function and blood pressure. J Clin Invest 2005; 115:1275–1280.

    CAS  Article  Google Scholar 

  21. Desir GV, Peixoto AJ. Renalase in hypertension and kidney disease. Nephrol Dial Transplant 2014; 29:22–28.

    CAS  Article  Google Scholar 

  22. Lee HT, Kim JY, Kim M, Wang P, Tang L, Baroni S, et al. Renalase protects against ischemic AKI. J Am Soc Nephrol 2013; 24:445–455.

    CAS  Article  Google Scholar 

  23. Wang L, Velazquez H, Moeckel G, Chang J, Ham A, Lee HT, et al. Renalase prevents AKI independent of amine oxidase activity. J Am Soc Nephrol 2014; 25:1226–1235.

    CAS  Article  Google Scholar 

  24. Fischer UM, Weissenberger WK, Warters RD, Geissler HJ, Allen SJ, Mehlhorn U. Impact of cardiopulmonary bypass management on postcardiac surgery renal function. Perfusion 2002; 17:401–406.

    Article  Google Scholar 

  25. Desir G. Novel insights into the physiology of renalase and its role in hypertension and heart disease. Pediatr Nephrol 2012; 27:719–725.

    Article  Google Scholar 

  26. Wasilewski G, Przybylowski P, Janik L, Nowak E, Sadowski J, Malyszko J. Dopamine and noradrenaline are unrelated to renalase, heart rate, and blood pressure in heart transplant recipients. Transplant Proc 2014; 46

  27. Baraka A, El Ghotny S. Cardioprotective effect of renalase in 5/6 nephrectomized rats. J Cardiovasc Pharmacol Ther 2012; 17:412–416.

    CAS  Article  Google Scholar 

  28. Gu R, Lu W, Xie J, Bai J, Xu B. Renalase deficiency in heart failure model of rats-a potential mechanism underlying circulating norepinephrine accumulation. PloS One 2011; 6:e14633.

  29. Haase-Fielitz A, Haase M, Bellomo R, Lambert G, Matalanis G, Story D, et al. Decreased catecholamine degradation associates with shock and kidney injury after cardiac surgery. J Am Soc Nephrol 2009; 20:1393–1403.

    CAS  Article  Google Scholar 

  30. Lassnigg A, Schmidlin D, Mouhieddine M, Bachmann LM, Druml W, Bauer P, et al. Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: a prospective cohort study. J Am Soc Nephrol 2004; 15:1597–1605.

    CAS  Article  Google Scholar 

  31. Parikh CR, Thiessen-Philbrook H, Garg AX, Kadiyala D, Shlipak MG, Koyner JL, et al. Performance of kidney injury molecule-1 and liver fatty acid-binding protein and combined biomarkers of AKI after cardiac surgery. Clin J Am Soc Nephrol 2013; 8:1079–1088.

    CAS  Article  Google Scholar 

  32. Han WK, Wagener G, Zhu Y, Wang S, Lee HT. Urinary biomarkers in the early detection of acute kidney injury after cardiac surgery. Clin J Am Soc Nephrol 2009; 4:873–882.

    CAS  Article  Google Scholar 

  33. Liu KD, Altmann C, Smits G, Krawczeski CD, Edelstein CL, Devarajan P, et al. Serum interleukin-6 and interleukin-8 are early biomarkers of acute kidney injury and predict prolonged mechanical ventilation in children undergoing cardiac surgery: a case-control study. Crit Care 2009; 13:R104.

  34. Xin C, Yulong X, Yu C, Changchun C, Feng Z, Xinwei M. Urine neutrophil gelatinase-associated lipocalin and interleukin-18 predict acute kidney injury after cardiac surgery. Ren Fail 2008; 30:904–913.

    Article  Google Scholar 

  35. Haase-Fielitz A, Bellomo R, Devarajan P, Story D, Matalanis G, Dragun D, et al. Novel and conventional serum biomarkers predicting acute kidney injury in adult cardiac surgery – a prospective cohort study. Crit Care Med 2009; 37:553–560.

    CAS  Article  Google Scholar 

  36. Ho J, Tangri N, Komenda P, Kaushal A, Sood M, Brar R, et al. Urinary, plasma, and serum biomarkers’ utility for predicting acute kidney injury associated with cardiac surgery in adults: a meta-analysis. Am J Kidney Dis 2015; 66:993–1005.

    CAS  Article  Google Scholar 

  37. Yap SC, Lee HT. Acute kidney injury and extrarenal organ dysfunction: new concepts and experimental evidence. Anesthesiology 2012; 116:1139–1148.

    Article  Google Scholar 

  38. Guo X, Wang L, Velazquez H, Safirstein R, Desir GV. Renalase: its role as a cytokine, and an update on its association with type 1 diabetes and ischemic stroke. Curr Opin Nephrol Hypertens 2014; 23:513–518.

    CAS  Article  Google Scholar 

  39. Du M, Huang K, Huang D, Yang L, Gao L, Wang X, et al. Renalase is a novel target gene of hypoxia-inducible factor-1 in protection against cardiac ischaemia-reperfusion injury. Cardiovasc Res 2015; 105:182–191.

    CAS  Article  Google Scholar 

  40. Wang F, Zhang G, Xing T, Lu Z, Li J, Peng C, et al. Renalase contributes to the renal protection of delayed ischaemic preconditioning via the regulation of hypoxia-inducible factor-1alpha. J Cell Mol Med 2015; 19: 1400–1409.

    CAS  Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ihab A. Ibrahim MD, PhD.

Additional information

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work noncommercially, as long as the author is credited and the new creations are licensed under the identical terms

Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Ibrahim, I.A., Sayed, H.A. & Mohammed, A.A. Plasma renalase as a biomarker of acute kidney injury after cardiac surgery. Egypt J Intern Med 28, 91–98 (2016). https://doi.org/10.4103/1110-7782.200966

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.4103/1110-7782.200966

Keywords

  • acute kidney injury
  • cardiac surgery
  • renalase