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Transplant Direct. 2015 Mar 10;1(2):e6. doi: 10.1097/TXD.0000000000000515. eCollection 2015 Mar.

Cyclic Helix B Peptide in Preservation Solution and Autologous Blood Perfusate Ameliorates Ischemia-Reperfusion Injury in Isolated Porcine Kidneys.

Transplantation direct

Cheng Yang, Sarah A Hosgood, Patel Meeta, Yaqiu Long, Tongyu Zhu, Michael L Nicholson, Bin Yang

Affiliations

  1. Department of Urology, Zhongshan Hospital, Fudan University; Shanghai Key Laboratory of Organ Transplantation, Shanghai, People's Republic of China.
  2. Transplant Group, Department of Infection, Immunity and Inflammation, University of Leicester, Leicester General Hospital, University Hospitals of Leicester, United Kingdom.
  3. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People's Republic of China.
  4. Transplant Group, Department of Infection, Immunity and Inflammation, University of Leicester, Leicester General Hospital, University Hospitals of Leicester, United Kingdom.; Renal Group, Basic Medical Research Centre; Department of Nephrology, Affiliated Hospital of Nantong University, University of Nantong, Nantong, People's Republic of China.

PMID: 27500213 PMCID: PMC4946457 DOI: 10.1097/TXD.0000000000000515

Abstract

UNLABELLED: There is a critical need to better preserve isolated organs before transplantation. We developed a novel nonerythropoiesis cyclic helix B peptide (CHBP) derived from erythropoietin, which has potent tissue protection and prolonged serum stability. The renoprotection and potential mechanism of CHBP were evaluated in a kidney preservation model.

MATERIALS AND METHODS: Porcine kidneys (n = 5) subjected to 20-minute warm ischemia were retrieved and flushed with hyperosmolar citrate to mimic deceased donation. The kidneys and autologous blood ± 10.56 nmol/L CHBP were placed in cold storage (CS) for 18 hours. These kidneys were then normothermically hemoreperfused for 3 hours using an isolated organ perfusion system. The renal function and structure, apoptosis, inflammation, and expression of caspase-3 and heat shock protein 70 (HSP70) were assessed.

RESULTS: Cyclic helix B peptide significantly increased the renal blood flow, oxygen consumption, and urine output during reperfusion, but decreased serum potassium and renal tissue damage. Apoptotic cells were significantly decreased in the tubular areas, but increased in the lumens and interstitial areas in the post-CS and postreperfused kidneys, whereas myeloperoxidase+ cells were reduced. In addition, the expression of both caspase-3 precursor and active subunits was downregulated by CHBP in reperfused kidneys. However, HSP70 was upregulated in the post-CS and postreperfused kidneys treated with CHBP.

CONCLUSIONS: Cyclic helix B peptide administered into preservation and reperfusion solutions ameliorated renal ischemia-reperfusion injury, which might be associated with decreased apoptosis, inflammation and caspase-3, but increased HSP70. This novel preservation approach using CHBP may be applied in a porcine kidney transplant model and potential human donor kidney preservation.

References

  1. Mol Ther. 2014 Oct;22(10):1817-28 - PubMed
  2. J Clin Invest. 1995 Apr;95(4):1854-60 - PubMed
  3. FASEB J. 2003 Sep;17(12):1754-5 - PubMed
  4. Exp Biol Med (Maywood). 2013 Jan;238(1):111-9 - PubMed
  5. Transplantation. 2014 Jun 27;97(12):1272-8 - PubMed
  6. Transpl Int. 2008 May;21(5):495-501 - PubMed
  7. Eur J Pharmacol. 2011 Jun 25;660(2-3):420-30 - PubMed
  8. Mol Med. 2012 May 09;18:719-27 - PubMed
  9. J Surg Res. 2012 Jul;176(1):260-6 - PubMed
  10. Am J Transplant. 2005 Jan;5(1):68-75 - PubMed
  11. Mol Pharmacol. 2003 Aug;64(2):334-45 - PubMed
  12. Clin J Am Soc Nephrol. 2012 Sep;7(9):1498-506 - PubMed
  13. Kidney Int. 2012 Feb;81(3):314-20 - PubMed
  14. Am J Transplant. 2003 Mar;3(3):273-80 - PubMed
  15. J Pain Symptom Manage. 2004 Feb;27(2):185-90 - PubMed
  16. Pharmacol Ther. 2010 Dec;128(3):445-59 - PubMed
  17. Ann Clin Lab Sci. 2005 Spring;35(2):161-8 - PubMed
  18. Transplantation. 2010 Apr 15;89(7):830-7 - PubMed
  19. Nature. 2007 Jan 4;445(7123):102-5 - PubMed
  20. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10925-30 - PubMed
  21. Transplantation. 2008 Aug 15;86(3):445-51 - PubMed
  22. J Transl Med. 2014 Feb 23;12:53 - PubMed
  23. Eur J Hum Genet. 2006 Mar;14(3):266-72 - PubMed
  24. Transplantation. 2011 Mar 15;91(5):501-7 - PubMed
  25. Transplantation. 2008 Jan 15;85(1):88-92 - PubMed
  26. Eukaryot Cell. 2011 Sep;10(9):1148-55 - PubMed
  27. Eur J Clin Invest. 2011 Mar;41(3):233-40 - PubMed
  28. J Clin Invest. 1994 Feb;93(2):759-67 - PubMed
  29. Mol Med. 2009 Jul-Aug;15(7-8):235-41 - PubMed
  30. J Surg Res. 2013 May;181(2):342-54 - PubMed
  31. Transpl Int. 2014 Mar;27(3):241-8 - PubMed
  32. Mol Med. 2002 Aug;8(8):495-505 - PubMed
  33. Mol Med. 2011 Mar-Apr;17(3-4):194-200 - PubMed
  34. J Intern Med. 2008 Nov;264(5):405-32 - PubMed
  35. Biochim Biophys Acta. 2014 Nov;1842(11):2306-17 - PubMed
  36. Molecules. 2014 Jun 23;19(6):8503-17 - PubMed
  37. Am J Transplant. 2010 Jul;10 (7):1695-700 - PubMed
  38. Molecules. 2013 Oct 16;18(10 ):12809-19 - PubMed
  39. Exp Clin Transplant. 2009 Jun;7(2):78-93 - PubMed
  40. Semin Thromb Hemost. 2010 Jul;36(5):537-49 - PubMed
  41. J Am Soc Nephrol. 2006 Jun;17(6):1503-20 - PubMed

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