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Ischaemic and inflammatory injury in renal graft from brain death donation: an update review

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Abstract

Renal transplantation remains an important therapy in treating renal failure and can be considered to be a curative treatment. The demand for renal grafts outstrips supply available each year, making it increasingly important to look at improving the treatment of both renal grafts and recipients, and thereby improving patient outcomes and increasing the pool of potential donor grafts. Important to this, however, is knowledge of the underlying mechanisms leading to damage to the graft and rejection from the recipient. This includes ischaemia and consequently the priming of the organ during storage for ischaemia reperfusion injury (IRI) on implantation and the importance of the innate immune system which can be activated via multiple pathways, often via TLR-4, and the consequent production of danger-associated molecular patterns. This makes the time period involving both explantation and storage an important therapeutic window for improving outcomes. Other windows explored include treatment of IRI and improvement in immunosuppressive therapy. The multiple windows of potential therapeutic input have spawned a large body of work exploring both the underlying mechanisms and also how to exploit these mechanisms to improve overall outcomes and to allow for more marginal organs to be used.

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References

  1. Liem YS, Bosch JL, Arends LR, Heijenbrok-Kal MH, Hunink MG. Quality of life assessed with the medical outcomes study short form 36-item health survey of patients on renal replacement therapy: a systematic review and meta-analysis. Value Health. 2007;10(5):390–7.

    Article  PubMed  Google Scholar 

  2. Matesanz RE. International figures on donation and transplantation 2011. Madrid: Council of Europe, 2012 September. Report No.: ISSN: 2171-4118 Contract No.: 1.

  3. Trivedi H, Szabo A, Hariharan S. Declining rates of deceased donor renal transplantation in the United States over successive years of listing. Am J Med. 2012;125(1):57–65.

    Article  PubMed  Google Scholar 

  4. Metzger RA, Delmonico FL, Feng S, Port FK, Wynn JJ, Merion RM. Expanded criteria donors for kidney transplantation. Am J Transplant. 2003;3:114–25.

    Article  PubMed  Google Scholar 

  5. Saidi RF, Elias N, Kawai T, Hertl M, Farrell ML, Goes N, Wong W, Hartono C, Fishman JA, Kotton CN, Tolkoff-Rubin N, Delmonico FL, Cosimi AB, Ko DSC. Outcome of kidney transplantation using expanded criteria donors and donation after cardiac death kidneys: realities and costs. Am J Transplant. 2007;7(12):2769–74.

    Article  CAS  PubMed  Google Scholar 

  6. Stratta RJ, Rohr MS, Sundberg AK, Armstrong G, Hairston G, Hartmann E, Farney AC, Roskopf J, Iskandar SS, Adams PL. Increased kidney transplantation utilizing expanded criteria deceased organ donors with results comparable to standard criteria donor transplant. Ann Surg. 2004;239(5):688–95 (discussion 95–7).

  7. Roodnat JI, van Riemsdijk IC, Mulder PG, Doxiadis I, Claas FH, Ijzermans JN, van Gelder T, Weimar W. The superior results of living-donor renal transplantation are not completely caused by selection or short cold ischemia time: a single-center, multivariate analysis. Transplantation. 2003;75(12):2014–8.

    Article  CAS  PubMed  Google Scholar 

  8. Naderi GH, Mehraban D, Kazemeyni SM, Darvishi M, Latif AH. Living or deceased donor kidney transplantation: a comparison of results and survival rates among Iranian patients. Transplant Proc. 2009;41(7):2772–4.

    Article  CAS  PubMed  Google Scholar 

  9. Barlow AD, Metcalfe MS, Johari Y, Elwell R, Veitch PS, Nicholson ML. Case-matched comparison of long-term results of non-heart beating and heart-beating donor renal transplants. Br J Surg. 2009;96(6):685–91.

    Article  CAS  PubMed  Google Scholar 

  10. Summers DM, Johnson RJ, Allen J, Fuggle SV, Collett D, Watson CJ, Bradley JA. Analysis of factors that affect outcome after transplantation of kidneys donated after cardiac death in the UK: a cohort study. Lancet. 2010;376(9749):1303–11.

    Article  PubMed  Google Scholar 

  11. Transplant NBa. Organ donation and transplant-activity report 2012–2013. Bristol: 2013.

  12. Alonso A, Fernandez-Rivera C, Villaverde P, Oliver J, Cillero S, Lorenzo D, Valdes F. Renal transplantation from non-heart-beating donors: a single-center 10-year experience. Transplant Proc. 2005;37(9):3658–60.

    Article  CAS  PubMed  Google Scholar 

  13. Smith M. Physiologic changes during brain stem death—lessons for management of the organ donor. J Heart Lung Transpl. 2004;23(9, Supplement):S217–22.

    Article  Google Scholar 

  14. Shah VR. Aggressive management of multiorgan donor. Transplant Proc. 2008;40(4):1087–90.

    Article  CAS  PubMed  Google Scholar 

  15. Ranasinghe AM, Bonser RS. Endocrine changes in brain death and transplantation. Best Pract Res Clin Endocrinol Metab. 2011;25(5):799–812.

    Article  CAS  PubMed  Google Scholar 

  16. Jung GO, Yoon MR, Kim SJ, Sin MJ, Kim EY, Moon JI, Kim JM, Choi GS, Kwon CH, Cho JW, Lee SK. The risk factors of delayed graft function and comparison of clinical outcomes after deceased donor kidney transplantation: single-center study. Transplant Proc. 2010;42(3):705–9

    Article  CAS  PubMed  Google Scholar 

  17. Molnar MZ, Kovesdy CP, Mucsi I, Bunnapradist S, Streja E, Krishnan M, Kalantar-Zadeh K. Higher recipient body mass index is associated with post-transplant delayed kidney graft function. Kidney Int. 2011;80(2):218–24.

    Article  PubMed  Google Scholar 

  18. Meier-Kriesche H-U, Schold JD, Srinivas TR, Kaplan B. Lack of improvement in renal allograft survival despite a marked decrease in acute rejection rates over the most recent era. Am J Transplant. 2004;4(3):378–83.

    Article  PubMed  Google Scholar 

  19. Lefaucheur C, Loupy A, Hill GS, Andrade J, Nochy D, Antoine C, Gautreau C, Charron D, Glotz D, Suberbielle-Boissel C. Preexisting donor-specific HLA antibodies predict outcome in kidney transplantation. J Am Soc Nephrol JASN. 2010;21(8):1398–406.

    Article  PubMed  Google Scholar 

  20. Dunn TB, Noreen H, Gillingham K, Maurer D, Ozturk OG, Pruett TL, Bray RA, Gebel HM, Matas AJ. Revisiting traditional risk factors for rejection and graft loss after kidney transplantation. Am J Transplant. 2011;11(10):2132–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Lentine KL, Gheorghian A, Axelrod D, Kalsekar A, L’Italien G, Schnitzler MA. The implications of acute rejection for allograft survival in contemporary U.S. kidney transplantation. Transplantation. 2012;94(4):369–76.

    Article  PubMed  Google Scholar 

  22. El Ters M, Grande JP, Keddis MT, Rodrigo E, Chopra B, Dean PG, Stegall MD, Cosio FG. Kidney allograft survival after acute rejection, the value of follow-up biopsies. Am J Transplant. 2013;13(9):2334–41.

    Article  PubMed  Google Scholar 

  23. Yarlagadda SG, Coca SG, Formica RN Jr, Poggio ED, Parikh CR. Association between delayed graft function and allograft and patient survival: a systematic review and meta-analysis. Nephrol Dial Transplant. 2009;24(3):1039–47.

    Article  PubMed  Google Scholar 

  24. Zukowski M, Bohatyrewicz R, Biernawska J, Kotfis K, Knap R, Zegan M, Ostrowski M, Brykczynski M. Cause of death in multiorgan donors and its relation to the function of transplanted kidneys. Transplant Proc. 2009;41(8):2972–4.

    Article  CAS  PubMed  Google Scholar 

  25. Lee S, Shin M, Kim E, Kim J, Moon J, Jung G, Choi G, Kwon C, Joh J, Kim S. Donor characteristics associated with reduced survival of transplanted kidney grafts in Korea. Transplant Proc. 2010;42(3):778–81.

    Article  CAS  PubMed  Google Scholar 

  26. Chamberlain G, Baboolal K, Bennett H, Pockett RD, McEwan P, Sabater J, Sennfält K. The economic burden of posttransplant events in renal transplant recipients in Europe. Transplantation. 2014;97(8):854–61.

    PubMed  Google Scholar 

  27. Schrader H, Hall C, Zwetnow NN. Effects of prolonged supratentorial mass expansion on regional blood flow and cardiovascular parameters during the Cushing response. Acta Neurol Scand. 1985;72(3):283–94.

    Article  CAS  PubMed  Google Scholar 

  28. Hoeger S, Reisenbuechler A, Gottmann U, Doyon F, Braun C, Kaya Z, Seelen MA, van Son WJ, Waldherr R, Schnuelle P, Yard BA. Donor dopamine treatment in brain dead rats is associated with an improvement in renal function early after transplantation and a reduction in renal inflammation. Transpl Int. 2008;21(11):1072–80.

    CAS  PubMed  Google Scholar 

  29. Campbell SJ, Jiang Y, Davis AEM, Farrands R, Holbrook J, Leppert D, Anthony DC. Immunomodulatory effects of etanercept in a model of brain injury act through attenuation of the acute-phase response. J Neurochem. 2007;103(6):2245–55.

    Article  CAS  PubMed  Google Scholar 

  30. Skrabal CA, Thompson LO, Potapov EV, Southard RE, Joyce DL, Youker KA, Noon GP, Loebe M. Organ-specific regulation of pro-inflammatory molecules in heart, lung, and kidney following brain death. J Surg Res. 2005;123(1):118–25.

    Article  CAS  PubMed  Google Scholar 

  31. Higashida T, Kreipke CW, Rafols JA, Peng C, Schafer S, Schafer P, Ding JY, Dornbos D, Li X, Guthikonda M, Rossi NF, Ding Y. The role of hypoxia-inducible factor-1α, aquaporin-4, and matrix metalloproteinase-9 in blood-brain barrier disruption and brain edema after traumatic brain injury. J Neurosurg. 2011;114(1):92–101.

    Article  CAS  PubMed  Google Scholar 

  32. Cheadle C, Watkins T, Ehrlich E, Barnes K, Gaber AO, Hemmerich S, Rabb H. Effects of anti-adhesive therapy on kidney biomarkers of ischemia reperfusion injury in human deceased donor kidney allografts. Clin Transplant. 2011;25(5):766–75.

    Article  CAS  PubMed  Google Scholar 

  33. Damman J, Nijboer WN, Schuurs TA, Leuvenink HG, Morariu AM, Tullius SG, van Goor H, Ploeg RJ, Seelen MA. Local renal complement C3 induction by donor brain death is associated with reduced renal allograft function after transplantation. Nephrol Dial Transplant. 2011;26(7):2345–54.

    Article  CAS  PubMed  Google Scholar 

  34. van Werkhoven MB, Damman J, van Dijk MC, Daha MR, de Jong IJ, Leliveld A, Krikke C, Leuvenink HG, van Goor H, van Son WJ, Olinga P, Hillebrands JL, Seelen MA. Complement mediated renal inflammation induced by donor brain death: role of renal C5a–C5aR interaction. Am J Transplant. 2013;13(4):875–82.

    Article  PubMed  CAS  Google Scholar 

  35. de Vries DK, Lindeman JH, Ringers J, Reinders ME, Rabelink TJ, Schaapherder AF. Donor brain death predisposes human kidney grafts to a proinflammatory reaction after transplantation. Am J Transplant. 2011;11(5):1064–70.

    Article  PubMed  Google Scholar 

  36. Nijboer WN, Schuurs TA, van der Hoeven JA, Leuvenink HG, van der Heide JJ, van Goor H, Ploeg RJ. Effects of brain death on stress and inflammatory response in the human donor kidney. Transplant Proc. 2005;37(1):367–9.

    Article  CAS  PubMed  Google Scholar 

  37. Bouma HR, Ploeg RJ, Schuurs TA. Signal transduction pathways involved in brain death-induced renal injury. Am J Transplant. 2009;9(5):989–97.

    Article  CAS  PubMed  Google Scholar 

  38. Bulcao CF, D'Souza KM, Malhotra R, Staron M, Duffy JY, Pandalai PK, Jeevanandam V, Akhter SA. Activation of JAK-STAT and nitric oxide signaling as a mechanism for donor heart dysfunction. J Heart Lung Transplant. 2010;29(3):346–51.

    Article  PubMed  PubMed Central  Google Scholar 

  39. McKeown DW, Bonser RS, Kellum JA. Management of the heartbeating brain-dead organ donor. Br J Anaesth. 2012;108(Suppl 1):i96–107.

    Article  PubMed  Google Scholar 

  40. Kruger B, Krick S, Dhillon N, Lerner SM, Ames S, Bromberg JS, Lin M, Walsh L, Vella J, Fischereder M, Kramer BK, Colvin RB, Heeger PS, Murphy BT, Schroppel B. Donor Toll-like receptor 4 contributes to ischemia and reperfusion injury following human kidney transplantation. Proc Natl Acad Sci USA. 2009;106(9):3390–5339.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Morris P, Knechtle SJ. Kidney transplantation: principles and practice. Philadelphia: Elsevier Health Sciences; 2008.

    Google Scholar 

  42. van der Vliet JA, Warle MC, Cheung CL, Teerenstra S, Hoitsma AJ. Influence of prolonged cold ischemia in renal transplantation. Clin Transplant. 2011;25(6):E612–6.

    Article  PubMed  Google Scholar 

  43. Fonouni H, Jarahian P, Rad MT, Golriz M, Faridar A, Esmaeilzadeh M, Hafezi M, Macher-Goeppinger S, Longerich T, Orakcioglu B, Sakowitz OW. Evaluating the effects of extended cold ischemia on interstitial metabolite in grafts in kidney transplantation using microdialysis. Langenbeck’s Archives of Surgery/Deutsche Gesellschaft fur Chirurgie. 2013;398(1):87–97.

    Article  PubMed  Google Scholar 

  44. Snoeijs MG, Vink H, Voesten N, Christiaans MH, Daemen JW, Peppelenbosch AG, Tordoir JH, Peutz-Kootstra CJ, Buurman WA, Schurink GW, van Heurn LW. Acute ischemic injury to the renal microvasculature in human kidney transplantation. Am J Physiol Renal Physiol. 2010;299(5):F1134–40.

    Article  CAS  PubMed  Google Scholar 

  45. Fougeray S, Bouvier N, Beaune P, Legendre C, Anglicheau D, Thervet E, Pallet N. Metabolic stress promotes renal tubular inflammation by triggering the unfolded protein response. Cell Death Dis. 2011;2:e143.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Chappell D, Jacob M, Hofmann-Kiefer K, Rehm M, Welsch U, Conzen P, Becker BF. Antithrombin reduces shedding of the endothelial glycocalyx following ischaemia/reperfusion. Cardiovasc Res. 2009;83(2):388–96.

    Article  CAS  PubMed  Google Scholar 

  47. Mulivor AW, Lipowsky HH. Inflammation- and ischemia-induced shedding of venular glycocalyx. Am J Physiol-Heart Circu Physiol. 2004;286(5):H1672–80.

    Article  CAS  Google Scholar 

  48. Lipowsky HH, Gao L, Lescanic A. Shedding of the endothelial glycocalyx in arterioles, capillaries, and venules and its effect on capillary hemodynamics during inflammation. Am J Physiol-Heart Circu Physiol. 2011;301(6):H2235–45.

    Article  CAS  Google Scholar 

  49. Andonian S, Coulthard T, Smith AD, Singhal PS, Lee BR. Real-time quantitation of renal ischemia using targeted microbubbles: in vivo measurement of P-selectin expression. J Endourol. 2009;23(3):373–8.

    Article  PubMed  Google Scholar 

  50. Akhtar AM, Schneider JE, Chapman SJ, Jefferson A, Digby JE, Mankia K, Chen Y, McAteerMA, Wood KJ, Choudhury RP. In vivo quantification of VCAM-1 expression in renal ischemia reperfusion injury using non-invasive magnetic resonance molecular imaging. PLoS One. 2010;5(9):e12800.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Damman J, Daha MR, van Son WJ, Leuvenink HG, Ploeg RJ, Seelen MA. Crosstalk between complement and toll-like receptor activation in relation to donor brain death and renal ischemia-reperfusion injury. Am J Transplant. 2011;11(4):660–9.

    Article  CAS  PubMed  Google Scholar 

  52. Pedregosa J, Haidar A, Hirata A, Franco M, Gomes G, Bueno V. TLR2 and TLR4 expression after kidney ischemia and reperfusion injury in mice treated with FTY720. Int Immunopharmacol. 2011;11(9):1311–8.

    Article  CAS  PubMed  Google Scholar 

  53. Altemeier WA, Liles WC, Villagra-Garcia A, Matute-Bello G, Glenny RW. Ischemia-reperfusion lung injury is attenuated in MyD88-deficient mice. PLoS One. 2013;8(10):e77123.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Kim HJ, Lee JS, Kim A, Koo S, Cha HJ, Han J, Do Y, Kim K.M., Kwon BS, Mittler RS. TLR2 signaling in tubular epithelial cells regulates NK cell recruitment in kidney ischemia-reperfusion injury. J Immunol. 2013;191(5):2657–64.

    Article  CAS  PubMed  Google Scholar 

  55. Moreth K, Frey H, Hubo M, Zeng-Brouwers J, Nastase M-V, Hsieh LT-H, Haceni R, PfeilschifterJ, Lozzo RV, Schaefer L. Biglycan-triggered TLR-2-and TLR-4-signaling exacerbates the pathophysiology of ischemic acute kidney injury. Matrix Biol. 2014;34:143–51.

  56. Li J, Gong Q, Zhong S, Wang L, Guo H, Xiang Y, Ichim TE, Wang C-Y, Chen S, Gong F. Neutralization of the extracellular HMGB1 released by ischaemic-damaged renal cells protects against renal ischaemia–reperfusion injury. Nephrol Dial Transplant. 2011;26(2):469–78.

    Article  PubMed  CAS  Google Scholar 

  57. Amura CR, Renner B, Lyubchenko T, Faubel S, Simonian PL, Thurman JM. Complement activation and toll-like receptor-2 signaling contribute to cytokine production after renal ischemia/reperfusion. Mol Immunol. 2012;52(3–4):249–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Peng Q, Li K, Smyth LA, Xing G, Wang N, Meader L, Lu B, Sacks SH, Zhou W. C3a and C5a Promote renal ischemia-reperfusion injury. J Am Soc Nephrol. 2012;23(9):1474–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Wu H, Ma J, Wang P, Corpuz TM, Panchapakesan U, Wyburn KR, Chadban SJ. HMGB1 contributes to kidney ischemia reperfusion injury. J Am Soc Nephrol. 2010;21(11):1878–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Mkaddem SB, Pedruzzi E, Werts C, Coan, N, Bens M, Cluzeaud F, Goujon J-M, Ogier-Denis E, Vandewalle A. Heat shock protein gp96 and NAD (P) H oxidase 4 play key roles in Toll-like receptor 4-activated apoptosis during renal ischemia/reperfusion injury. Cell Death Differ. 2010;17(9):1474–85.

    Article  PubMed  CAS  Google Scholar 

  61. Gatti S, Bruno S, Deregibus MC, Sordi A, Cantaluppi V, Tetta C, Camussi G. Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury. Nephrol Dial Transplant. 2011;26(5):1474–83.

    Article  CAS  PubMed  Google Scholar 

  62. Serinsoz E, Bock O, Gwinner W, Schwarz A, Haller H, Kreipe H, Mengel M. Local complement C3 expression is upregulated in humoral and cellular rejection of renal allografts. Am J Transplant. 2005;5(6):1490–4.

    Article  PubMed  CAS  Google Scholar 

  63. Cravedi P, Leventhal J, Lakhani P, Ward SC, Donovan MJ, Heeger PS. Immune cell-derived C3a and C5a costimulate human T cell alloimmunity. Am J Transplant. 2013;13(10):2530–9.

    Article  CAS  PubMed  Google Scholar 

  64. Zuidwijk K, de Fijter JW, Mallat MJK, Eikmans M, van Groningen MC, Goemaere NN, BajemaI M, van Kooten C. Increased influx of myeloid dendritic cells during acute rejection is associated with interstitial fibrosis and tubular atrophy and predicts poor outcome. Kidney Int. 2012;81(1):64–75.

  65. Wavamunno MD, O'Connell PJ, Vitalone M, Fung CLS, Allen RDM, Chapman JR, Nankivell BJ. Transplant glomerulopathy: ultrastructural abnormalities occur early in longitudinal analysis of protocol biopsies. Am J Transplant. 2007;7(12):2757–68.

    Article  CAS  PubMed  Google Scholar 

  66. Haas M, Mirocha J. Early ultrastructural changes in renal allografts: correlation with antibody-mediated rejection and transplant glomerulopathy. Am J Transplant. 2011;11(10):2123–31.

    Article  CAS  PubMed  Google Scholar 

  67. Mascia L, Mastromauro I, Viberti S, Vincenzi M, Zanello M. Management to optimize organ procurement in brain dead donors. Minerva Anestesiol. 2009;75(3):125–33.

    CAS  PubMed  Google Scholar 

  68. Chamorro C, Falcón JA, Michelena JC. Controversial points in organ donor management. Transplant Proc. 2009;41(8):3473–5.

    Article  CAS  PubMed  Google Scholar 

  69. Schaub M, Ploetz CJ, Gerbaulet D, Fang L, Kranich P, Stadlbauer TH, Goettman U, Yard BA, Braun C, Schnuelle P, van der Woude FJ. Effect of dopamine on inflammatory status in kidneys of brain-dead rats. Transplantation. 2004;77(9):1333–40.

    Article  CAS  PubMed  Google Scholar 

  70. Schnuelle P, Gottmann U, Hoeger S, Boesebeck D, Lauchart W, Weiss C, Fischereder M, JauchKW, Heemann U, Zeier M, Hugo C. Effects of donor pretreatment with dopamine on graft function after kidney transplantation: a randomized controlled trial. JAMA. 2009;302(10):1067–75.

    Article  CAS  PubMed  Google Scholar 

  71. Liu Z, Hoeger S, Schnuelle P, Feng Y, Goettmann U, Waldherr R, van der Woude FJ, Yard B. Donor dopamine pretreatment inhibits tubulitis in renal allografts subjected to prolonged cold preservation. Transplantation. 2007;83(3):297–303.

    Article  CAS  PubMed  Google Scholar 

  72. Nijboer WN, Ottens PJ, van Dijk A, van Goor H, Ploeg RJ, Leuvenink HGD. Donor pretreatment with carbamylated erythropoietin in a brain death model reduces inflammation more effectively than erythropoietin while preserving renal function*. Crit Care Med. 2010;38(4):1155–61. doi:10.097/CCM.0b013e3181cf6e78.

    Article  CAS  PubMed  Google Scholar 

  73. Jia RP, Zhu JG, Wu JP, Xie JJ, Xu LW. Experimental study on early protective effect of ischemic preconditioning on rat kidney graft. Transplant Proc. 2009;41(1):69–72.

    Article  CAS  PubMed  Google Scholar 

  74. Chen Y, Zheng H, Wang X, Zhou Z, Luo A, Tian Y. Remote ischemic preconditioning fails to improve early renal function of patients undergoing living-donor renal transplantation: a randomized controlled trial. Transplantation. 2013;95(2):e4–6. doi:10.1097/TP.0b013e3182782f3a.

    Article  PubMed  Google Scholar 

  75. Zhang L, Huang H, Cheng J, Liu J, Zhao H, Vizcaychipi MP, Ma D. Pre-treatment with isoflurane ameliorates renal ischemic–reperfusion injury in mice. Life Sci. 2011;88(25–26):1102–7.

    Article  CAS  PubMed  Google Scholar 

  76. Vianna PTG, Castiglia YMM, Braz JRC, Viero RM, Beier S, Vianna Filho PTG, Vitória A, Reinoldes Bizarria Guilherme G, de Assis Golim M, Deffune E. Remifentanil, isoflurane, and preconditioning attenuate renal ischemia/reperfusion injury in rats. Transplant Proc. 2009;41(10):4080–2.

    Article  CAS  PubMed  Google Scholar 

  77. Ma D, Lim T, Xu J, Tang H, Wan Y, Zhao H, Hossain M, Maxwell PH, Maze M. Xenon preconditioning protects against renal ischemic-reperfusion injury via HIF-1α activation. J Am Soc Nephrol. 2009;20(4):713–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Zhao H, Watts HR, Chong M, Huang H, Tralau-Stewart C, Maxwell PH, Maze M, George AJT, Ma D. Xenon treatment protects against cold ischemia associated delayed graft function and prolongs graft survival in rats. Am J Transplant. 2013;13(8):2006–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Damman J, Hoeger S, Boneschansker L, Theruvath A, Waldherr R, Leuvenink HG, Ploeg RJ, Yard BA, Seelen MA. Targeting complement activation in brain-dead donors improves renal function after transplantation. Transpl Immunol. 2011;24(4):233–7.

    Article  CAS  PubMed  Google Scholar 

  80. Catena F, Coccolini F, Montori G, Vallicelli C, Amaduzzi A, Ercolani G, Ravaioli M, Del Gaudio M, Schiavina R, Brunocilla E, Liviano G, Feliciangeli G, Pinna AD. Kidney preservation: review of present and future perspective. Transplant Proc. 2013;45(9):3170–7.

    Article  CAS  PubMed  Google Scholar 

  81. Yuan X, Theruvath AJ, Ge X, Floerchinger B, Jurisch A, Garcia-Cardena G, Tullius SG. Machine perfusion or cold storage in organ transplantation: indication, mechanisms, and future perspectives. Transpl Int. 2010;23(6):561–70.

    Article  PubMed  Google Scholar 

  82. Koetting M, Frotscher C, Minor T. Hypothermic reconditioning after cold storage improves postischemic graft function in isolated porcine kidneys. Transpl Int. 2010;23(5):538–42.

    Article  PubMed  Google Scholar 

  83. Zhao H, Ning J, Savage S, Kang H, Lu K, Zheng X, George AJ, Ma D. A novel strategy for preserving renal grafts in an ex vivo setting: potential for enhancing the marginal donor pool. FASEB J. 2013;27(12):4822–33.

    Article  CAS  PubMed  Google Scholar 

  84. Moers C Smits JM, Maathuis MH, Treckmann J, van Gelder F, Napieralski BP, van Kasterop-Kutz M, van der Heide JJ, Squifflet JP, van Heurn E, Kirste GR, Rahmel A, Leuvenink HG, Paul A, Pirenne J, Ploeg RJ. Machine perfusion or cold storage in deceased-donor kidney transplantation. N Engl J Med. 2009;360(1):7–19.

    Article  CAS  PubMed  Google Scholar 

  85. Kayler LK, Magliocca J, Zendejas I, Srinivas TR, Schold JD. Impact of cold ischemia time on graft survival among ECD transplant recipients: a paired kidney analysis. Am J Transplant. 2011;11(12):2647–56.

    Article  CAS  PubMed  Google Scholar 

  86. Hosgood SA, Barlow AD, Yates PJ, Snoeijs MG, van Heurn EL, Nicholson ML. A pilot study assessing the feasibility of a short period of normothermic preservation in an experimental model of non heart beating donor kidneys. J Surg Res. 2011;171(1):283–90.

    Article  PubMed  Google Scholar 

  87. Brasile L, Stubenitsky BM, Haisch CE, Kon M, Kootstra G. Repair of damaged organs in vitro. Am J Transplant. 2005;5(2):300–6.

    Article  PubMed  Google Scholar 

  88. Nicholson ML, Hosgood SA. Renal transplantation after ex vivo normothermic perfusion: the first clinical study. Am J Transplant. 2013;13(5):1246–52.

    Article  CAS  PubMed  Google Scholar 

  89. Sharples EJ, Patel N, Brown P, Stewart K, Mota-Philipe H, Sheaff M, Kieswich J, Allen D, Harwood S, Raftery M, Thiemermann C, Yaqoob MM. Erythropoietin protects the kidney against the injury and dysfunction caused by ischemia-reperfusion. J Am Soc Nephrol. 2004;15(8):2115–24.

    Article  CAS  PubMed  Google Scholar 

  90. Spandou E, Tsouchnikas I, Karkavelas G, Dounousi E, Simeonidou C, Guiba-Tziampiri O, TsakirisD. Erythropoietin attenuates renal injury in experimental acute renal failure ischaemic/reperfusion model. Nephrol Dial Transplant. 2006;21(2):330–6.

    Article  CAS  PubMed  Google Scholar 

  91. Cai Z, Semenza GL. Phosphatidylinositol-3-kinase signaling is required for erythropoietin-mediated acute protection against myocardial ischemia/reperfusion injury. Circulation. 2004;109(17):2050–3.

    Article  CAS  PubMed  Google Scholar 

  92. Caumartin Y, Stephen J, Deng JP, Lian D, Lan Z, Liu W, Garcia B, Jevnikar AM, Wang H, Cepinskas G. Carbon monoxide-releasing molecules protect against ischemia–reperfusion injury during kidney transplantation. Kidney Int. 2011;79(10):1080–9.

    Article  CAS  PubMed  Google Scholar 

  93. Obal D, Rascher K, Favoccia C, Dettwiler S, Schlack W. Post-conditioning by a short administration of desflurane reduced renal reperfusion injury after differing of ischaemia times in rats. Br J Anaesth. 2006;97(6):783–91.

    Article  CAS  PubMed  Google Scholar 

  94. Jiang B, Liu X, Chen H, Liu D, Kuang Y, Xing B, Chen Z. ischemic postconditioning attenuates renal ischemic/reperfusion injury in mongrel dogs. Urology. 2010;76(6):1519.e1–7.

  95. Wang JM, Hu ZY, Gu WZ. Effects of sevoflurane postconditioning on renal ischemia-reperfusion injury: experiment with rats. Zhonghua yi xue za zhi. 2009;89(15):1016–20.

    CAS  PubMed  Google Scholar 

  96. Song JH, Kim M, Park SW, Chen SW, Pitson SM, Lee HT. Isoflurane via TGF-β1 release increases caveolae formation and organizes sphingosine kinase signaling in renal proximal tubules. Am J Physiol-Renal Physiol. 2010;298(4):F1041.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Kim M, Ham A, Kim JY, Brown KM, D’Agati VD, Lee HT. The volatile anesthetic isoflurane induces ecto-5′-nucleotidase (CD73) to protect against renal ischemia and reperfusion injury. Kidney Int. 2013;84(1):90–103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Zhao H, Yoshida A, Xiao W, Ologunde R, O'Dea KP, Takata M, Tralau-Stewart C, George AJT, Ma D. Xenon treatment attenuates early renal allograft injury associated with prolonged hypothermic storage in rats. FASEB J. 2013;27(10):4076–88.

    Article  CAS  PubMed  Google Scholar 

  99. Kong HY, Zhu SM, Wang LQ, He Y, Xie HY, Zheng SS. Sevoflurane protects against acute kidney injury in a small-size liver transplantation model. Am J Nephrol. 2010;32(4):347–55.

    Article  CAS  PubMed  Google Scholar 

  100. Hanto DW, Maki T, Yoon MH, Csizmadia E, Chin BY, Gallo D, Konduru B, Kuramitsu K, Smith NR, Berssenbrugge A, Attanasio C, Thomas M, Wegiel B, Otterbein LE. Intraoperative administration of inhaled carbon monoxide reduces delayed graft function in kidney allografts in swine. Am J Transplant. 2010;10(11):2421–30.

    Article  CAS  PubMed  Google Scholar 

  101. Lee R-A, Gabardi S. Current trends in immunosuppressive therapies for renal transplant recipients. Am J Health-Syst Pharm. 2012;69(22):1961–75.

  102. Knight SR, Russell NK, Barcena L, Morris PJ. Mycophenolate mofetil decreases acute rejection and may improve graft survival in renal transplant recipients when compared with azathioprine: a systematic review. Transplantation. 2009;87(6):785–94.

    Article  CAS  PubMed  Google Scholar 

  103. Gabardi S, Baroletti SA. Everolimus: a proliferation signal inhibitor with clinical applications in organ transplantation, oncology, and cardiology. Pharmacother J Human Pharmacol Drug Ther. 2010;30(10):1044–56.

    Article  CAS  Google Scholar 

  104. Mittal T, Kohli HS. Post renal transplant acute kidney injury. Indian J Transplant. 2014;8(Supplement 1):S33–6.

    Article  Google Scholar 

  105. Hadimioglu N, Saadawy I, Saglam T, Ertug Z, Dinckan A. The effect of different crystalloid solutions on acid-base balance and early kidney function after kidney transplantation. Anesth Analg. 2008;107(1):264–9.

    Article  CAS  PubMed  Google Scholar 

  106. Potura E, Lindner G, Biesenbach P, Funk GC, Reiterer C, Kabon B, Schwarz C, Druml W, Fleischmann E. An acetate-buffered balanced crystalloid versus 0.9% saline in patients with end-stage renal disease undergoing cadaveric renal transplantation: a prospective randomized controlled trial. Anesth Analg. 2015;120(1):123–9.

    Article  CAS  PubMed  Google Scholar 

  107. Lobo DN, Awad S. Should chloride-rich crystalloids remain the mainstay of fluid resuscitation to prevent/‘pre-renal/’ acute kidney injury[quest]: con. Kidney Int. 2014;86(6):1096–105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Schnuelle P, Johannes van der Woude F. Perioperative fluid management in renal transplantation: a narrative review of the literature. Transpl Int. 2006;19(12):947–59.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank Mr. Jonathan Balallo for his contribution to the creation of the images for this review.

Funding

This work was supported by the BJA/RCoA Research Fellowship grant, London, UK.

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Authors and Affiliations

  1. Department of Anesthesiology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China

    Anthony Fung & Qingqian Lian

  2. Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, UK

    Anthony Fung, Hailin Zhao, Bob Yang & Daqing Ma

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  1. Anthony Fung
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  2. Hailin Zhao
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  3. Bob Yang
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  4. Qingqian Lian
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Corresponding authors

Correspondence to Qingqian Lian or Daqing Ma.

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Fung, A., Zhao, H., Yang, B. et al. Ischaemic and inflammatory injury in renal graft from brain death donation: an update review. J Anesth 30, 307–316 (2016). https://doi.org/10.1007/s00540-015-2120-y

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  • DOI: https://doi.org/10.1007/s00540-015-2120-y

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