Ilker AKAR, Muzaffer KATAR

Is C-type natriuretic peptid level can be an early ındicator for acute kidney ınjury?

Acute kidney injury (AKI) is defined as a reduction of renal function in hours, including both structural damage and loss of function. There are limited number of biomarkers for early detection and staging of severity. C-type natriuretic peptide (CNP) has been detected in at several tissues. We aimed to evaluate plasma CNP and creatinine levels correlated with duration of ischemia in an experimentally induced AKI rat model. Forty male Sprague-Dawley type rats (aged 8 to 12 weeks, weighing 250-350 g) were used. The animals were randomly seperated into 4 groups: Group 1(n:10): Only laparotomy was performed. The left renal artery was clamped for 3, 6 and 9 hours in groups 2 ( n:10), 3 (n:10) and 4 (n:10) respectively. CNP and creatinine levels were measured in serum samples from rats. A significant increase in creatinine levels was determined in group 2 according to group 1 (p=0.006). The mean plasma creatinine values in group 3 and 4 were decreased compared to group 2 but this difference was not statistically significant (p=0.0862). The mean CNP level in Group 2 (39.5 ± 7.93 mg/dl) was found numerically higher than group 1 (37.90 ± 5.38mg/dl). There was a statistically insignificant decrease in mean CNP levels in group 3 and 4 compared with group 2. Renal ischemia increases the level of CNP. Although the increase in CNP levels is not significant, it can be said that clinical and experimental studies evaluating the timing of ischemia involving different durations should be performed.

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1. Ostermann M, Liu K. Pathophysiology of AKI. Best Pract Res Clin Anaesthesiol. 2017;31:305-14.

2. Makris K, Spanou L. Acute Kidney Injury: Definition, Pathophysiology and Clinical Phenotypes. Clin Biochem Rev. 2016;37:85-98.

3. Park Y, Hirose R, Dang K, et al. Increased severity of renal ischemia-reperfusion injury with venous clamping compared to arterial clamping in a rat model. Surgery. 2008;143:243-51.

4. Coca SG, Yalavarthy R, Concato J, et al. Biomarkers for the diagnosis and risk stratification of acute kidney injury: a systematic review. Kidney Int. 2008;73:1008–16.

5. Murray RL, Mehta A, Shaw C, et al. Kellum Current use of biomarkers in acute kidney injury: report and summary of recommendations from the 10th Acute Dialysis Quality Initiative consensus conference Kidney Int. 2014;85:513-21.

6. Murray PT. Acute kidney injury biomarkers and endpoints for clinical trials. Contrib Nephrol. 2011;171:208-12.

7. Herget-Rosenthal S, Marggraf G, Husing J, et al. Early detection of acuterenal failure by serum cystatin C. Kidney Int. 2004;66:1115–22.

8. Parikh CR, Abraham E, Ancukiewicz M, et al. Urine IL-18 is an earlydiagnostic marker for acute kidney injury and predicts mortality in theintensive care unit. J Am Soc Nephrol. 2005;16:3046–52.

9. Mishra J, Dent C, Tarabishi Ret al. Neutrophil gelatinase-associatedlipocalin (NGAL) as a biomarker for acute renal injury after cardiacsurgery. Lancet. 2005;365:1231–8.

10. Han WK, Bailly V, Abichandani Ret al. Kidney injury molecule-1 (KIM-1): anovel biomarker for human renal proximal tubule injury.Kidney Int. 2002;62:237–44

11. Guerci P, Ergin B, Ince C. The macro- and microcirculation of the kidney. Best Pract Res Clin Anaesthesiol. 2017;31:315-29.

12. Scotland RS, Ahluwalia A, Hobbs AJ. C-type natriuretic peptide in vascular physiology and disease. Pharmacol Ther. 2005;105:85-93.

13. Swärd K, Valsson F, Odencrants P, et al. Recombinant human atrial natriuretic peptide in ischemic acute renal failure: a randomized placebo-controlled trial. Crit Care Med. 2004;32:1310-5.

14. Staub D, Nusbaumer C, Zellweger MJ, et al. Use of B-type natriuretic peptide in the detection of myocardial ischemia. Am Heart J. 2006;151:1223- 30.

15. Nadir MA, Witham MD, Szwejkowski BR, et al. Meta-analysis of B-type natriuretic peptide’s ability to identify stress induced myocardial ischemia. Am J Cardiol. 2011;107:662-67.

16. Kumakura H, Kanai H, Araki Y, et al. Differences in brain natriuretic peptide and other factors between japanese peripheral arterial disease patients with critical limb ischemia and intermittent claudication. J Atheroscler Thromb. 2013;20:798-80.

17. Demirtas S, Karahan O, Yazici S, et al. Diagnostic value of plasma C-type natriuretic peptide levels in determination of the duration of mesenteric ischaemia. Cardiovasc J Afr. 2014;25:200-03.

18. Bonventre JV. Pathophysiology of acute kidney injury: roles of potential inhibitors of inflammation. Contrib Nephrol. 2007;156:39-46.

19. Sharfuddin AA, Molitoris BA. Pathophysiology of ischemic acute kidney injury. Nat Rev Nephrol. 2011;7:189-200.

20. Bonventre JV, Yang L. Cellular pathophysiology of ischemic acute kidney injury. J Clin Invest. 2011;121:4210-21.

21. Bonventre JV. Pathophysiology of AKI: injury and normal and abnormal repair. Contrib Nephrol. 2010;165:9-17.

22. Kashani K, Cheungpasitporn W, Ronco C. Biomarkers of acute kidney injury: the pathway from discovery to clinical adoption. Clin Chem Lab Med. 2017;55:1074-89.

23. Sudoh T, Minamino N, Kangawa K, et al. C-type natriuretic peptide (CNP). A new member of the natriuretic peptide family identified in porcine brain. Biochem Biophys Res Commun. 1990;168:863-70.

24. Barr CS, Rhodes P, Struthers AD. C-type natriuretic peptides. Peptides. 1996;17:1243-51.

25. Pandit K, Mukhopadhyay P, Ghosh S, et al. Natriuretic peptides: Diagnostic and therapeutic use. Indian J Endocrinol Metab. 2011;15:345-53.

26. Çalışkan A, Yazıcı S, Karahan O, et al. Use of C-type natriuretic peptide as an indicator in detection of inducible peripheral ischemia. Turkish J Thorac Cardiovasc Surg. 2014;22:615-9.

27. Zakeri R, Burnett JC Jr, Sangaralingham SJ. Urinary C-type natriuretic peptide: an emerging biomarker for heart failure and renal remodeling. Clin Chim Acta. 2015;443:108-13.

28. Hu P, Wang J, Hu B, et al. Increased urinary C-type natriuretic peptide excretion may be an early marker of renal tubulointerstitial fibrosis. Peptides. 2012;37:98-105.

29. Duffield JS, Park KM, Hsiao LL, et al. Restoration of tubular epithelial cells during repair of the postischemic kidney occurs independently of bone marrow-derived stem cells. J Clin Invest. 2005;115:1743-55

30. Boventre JV, Weinberg JM. Recent Advances in the Pathophysiology of Ischemic Acute Renal Failure. Am Soc Nephrol. 2003;14:2199–210.

31. Bonventre JV. Dedifferentiation and proliferation of surviving epithelial cells in acute renal failure. J Am Soc Nephrol. 2003;14:855–61.

32. Devarajan P, Mishra J, Supavekin S, et al. Gene expression in early ischemic renal injury: Clues towards pathogenesis, biomarker discovery, and novel therapeutics. Mol Genet Metab. 2003;80:365–76.

33. Hammerman MR. Recapitulation of phylogeny by ontogeny in nephrology. Kidney Int. 2000;57:742–55

34. Devarajan P. Update on mechanisms of ischemic acute kidney injury. J Am Soc Nephrol. 2006;17:1503-20.