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Ascorbic acid against reperfusion injury in human renal transplantation

  • Original Article
  • Published:
Transplant International

Abstract

The cadaveric renal graft is exposed to ischaemic injury during preservation and to oxidative damage during reperfusion. Both these mechanisms are known to cause cell damage, which may impair graft function. Reperfusion injury (RPI) is mediated by reactive oxygen species (ROS). Ascorbic acid (AA) is a potent physiological extracellular scavenger of ROS. We perfused 31 renal grafts immediately before implantation with a solution of Euro-Collins containing 0.5 mg/ml of AA to diminish RPI. From every donor, the contralateral kidney served as a control. The control grafts were perfused with the same perfusion as those of the AA group, only without the AA substitution. We assessed the effect of AA by recording serum creatinine, creatinine clearance, initial graft function and early rejections. The incidence of delayed graft function (DGF) was 32% in the AA group, and 29% in the control group. Other parameters were also similar in both groups, except for the length of DGF, which showed a trend towards a shorter duration in the AA group. The pre-operative systemic AA concentration was significantly (P=0.01) lower in the haemodialysis patients than in those on peritoneal dialysis. In conclusion, this clinical study could not demonstrate significant benefits of AA in renal transplantation.

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References

  1. Cecka JM, Terasaki PI (1995) The UNOS scientific renal transplant registry. United Network for Organ Sharing. Clin Transpl 1–18

  2. Crompton M, Ellinger H, Costi A (1988) Inhibition by cyclosporin A of a Ca2+-dependent pore in heart mitochondria activated by inorganic phosphate and oxidative stress. Biochem J 255:357–360

    CAS  PubMed  Google Scholar 

  3. Davenport A, Hopton M, Bolton C (1995) Measurement of malondialdehyde as a marker of oxygen free radical production during renal allograft transplantation and the effect on early graft function. Clin Transplant 9:171–175

    CAS  PubMed  Google Scholar 

  4. Dawidson IJ, Ar'Rajab A (1992) Perioperative fluid and drug therapy during cadaver kidney transplantation. Clin Transpl 267–284

  5. Dingchao H, Zhiduan Q, Liye H, Xiaodong F (1994) The protective effects of high-dose ascorbic acid on myocardium against reperfusion injury during and after cardiopulmonary bypass. Thorac Cardiovasc Surg 42:276–278

    CAS  PubMed  Google Scholar 

  6. Doppelfeld IS, Parnham MJ (1992) Experimental conditions determine effects of ascorbic acid on reperfusion injury: comparison of tissue damage with hemodynamic parameters in rat isolated hearts. Methods Find Exp Clin Pharmacol 14:419–430

    CAS  PubMed  Google Scholar 

  7. Feldman HI, Gayner R, Berlin JA, Roth DA, Silibovsky R, Kushner S, Brayman KL, Burns JE, Kobrin SM, Friedman AL, Grossman RA (1996) Delayed function reduces renal allograft survival independent of acute rejection. Nephrol Dial Transplant 11:1306–1313

    CAS  PubMed  Google Scholar 

  8. Halloran PF, Aprile MA, Farewell V, Ludwin D, Smith EK, Tsai SY, Bear RA, Cole EH, Fenton SS, Cattran DC (1988) Early function as the principal correlate of graft survival. A multivariate analysis of 200 cadaveric renal transplants treated with a protocol incorporating antilymphocyte globulin and cyclosporine. Transplantation 46:223–228

    CAS  PubMed  Google Scholar 

  9. Hower R, Minor T, Schneeberger H, Theodorakis J, Rembold S, Illner WD, Hofmann GO, Fraunberger P, Isselhard W, Land W (1996) Assessment of oxygen radicals during kidney transplantation—effect of radical scavenger. Transpl Int [Suppl] 9:479–482

    Google Scholar 

  10. Humar A, Johnson EM, Payne WD, Wrenshall L, Sutherland DE, Najarian JS, Gillingham KJ, Matas AJ (1997) Effect of initial slow graft function on renal allograft rejection and survival. Clin Transplant 11:623–627

    CAS  PubMed  Google Scholar 

  11. Koo DD, Welsh KI, Roake JA, Morris PJ, Fuggle SV (1998) Ischemia/reperfusion injury in human kidney transplantation: an immunohistochemical analysis of changes after reperfusion. Am J Pathol 153:557–566

    CAS  PubMed  Google Scholar 

  12. Kyllönen L, Salmela K (2000) Transplantation of both kidneys from 408 donors; comparison of results. Transpl Int [Suppl] 13:95–98

    Google Scholar 

  13. Kyllönen LE, Salmela KT, Eklund BH, Halme LE, Höckerstedt KA, Isoniemi HM, Mäkisalo HJ, Ahonen J (2000) Long-term results of 1047 cadaveric kidney transplantations with special emphasis on initial graft function and rejection. Transpl Int 13:122–128

    PubMed  Google Scholar 

  14. Land W, Schneeberger H, Schleibner S, Illner WD, Abendroth D, Rutili G, Arfors KE, Messmer K (1994) The beneficial effect of human recombinant superoxide dismutase on acute and chronic rejection events in recipients of cadaveric renal transplants. Transplantation 57:211–217

    CAS  PubMed  Google Scholar 

  15. Lee KC, Hamel DW, Kunbel S (1993) Rodent model of renal ischemia and reperfusion injury: influence of body temperature, seasonal variation, tumor necrosis factor, endogenous and exogenous antioxidants. Methods Find Exp Clin Pharmacol 15:153–159

    CAS  PubMed  Google Scholar 

  16. Lodge JP, Kashi SH, Lam FT, Lord A, Giles GR (1993) The reflush effect—a prospective analysis of late perfusion. Transplantation 55:567–572

    CAS  PubMed  Google Scholar 

  17. Lykkesfeldt J, Loft S, Poulsen HE (1995) Determination of ascorbic acid and dehydroascorbic acid in plasma by high-performance liquid chromatography with coulometric detection—are they reliable biomarkers of oxidative stress? Anal Biochem 229:329–335

    Google Scholar 

  18. Marcen R, Orofino L, Pascual J, de la Cal MA, Teruel JL, Villafruela JJ, Rivera ME, Mampaso F, Burgos FJ, Ortuno J (1998) Delayed graft function does not reduce the survival of renal transplant allografts. Transplantation 66:461–466

    CAS  PubMed  Google Scholar 

  19. Massoudy P, Mempel T, Raschke P, Becker BF (1999) Reduction of oxygen delivery during post-ischemic reperfusion protects the isolated guinea pig heart. Basic Res Cardiol 94:231–237

    Article  CAS  PubMed  Google Scholar 

  20. Masters TN, Fokin AA, Schaper J, Lorenz-Meyer S, Pool L, Gong G, Robicsek F (2000) Extending myocardial viability during heart preservation with cyclosporine A. J Card Surg 15:392–402

    CAS  PubMed  Google Scholar 

  21. Nakagawa K, Koo DD, Davies DR, Gray DW, McLaren AJ, Welsh KI, Morris PJ, Fuggle SV (2002) Lecithinized superoxide dismutase reduces cold ischemia-induced chronic allograft dysfunction. Kidney Int 61:1160–1169

    Article  PubMed  Google Scholar 

  22. Niki E (1991) Action of ascorbic acid as a scavenger of active and stable oxygen radicals. Am J Clin Nutr [Suppl] 54:1119–1124

    Google Scholar 

  23. Ojo AO, Wolfe RA, Held PJ, Port FK, Schmouder RL (1997) Delayed graft function: risk factors and implications for renal allograft survival. Transplantation 63:968–974

    CAS  Google Scholar 

  24. Perez Fontan M, Rodriguez-Carmona A, Bouza P, Valdes F (1998) The prognostic significance of acute renal failure after renal transplantation in patients treated with cyclosporin. QJM 91:27–40

    Article  PubMed  Google Scholar 

  25. Pfaff WW, Howard RJ, Patton PR, Adams VR, Rosen CB, Reed AI (1998) Delayed graft function after renal transplantation. Transplantation 65:219–223

    CAS  PubMed  Google Scholar 

  26. Ponka A, Kuhlback B (1983) Serum ascorbic acid in patients undergoing chronic hemodialysis. Acta Med Scand 213:305–307

    CAS  PubMed  Google Scholar 

  27. Roake JA, Fawcett J, Koo DD, Fuggle SV, Gray DW, Morris PJ (1996) Late reflush in clinical renal transplantation. Protection against delayed graft function not observed. Transplantation 62:114–116

    CAS  PubMed  Google Scholar 

  28. Rosenthal JT, Danovitch GM, Wilkinson A, Ettenger RB (1991) The high cost of delayed graft function in cadaveric renal transplantation. Transplantation 51:1115–1118

    CAS  PubMed  Google Scholar 

  29. Shah GM, Ross EA, Sabo A, Pichon M, Bhagavan H, Reynolds RD (1991) Ascorbic acid supplements in patients receiving chronic peritoneal dialysis. Am J Kidney Dis 18:84–90

    CAS  Google Scholar 

  30. Togashi H, Shinzawa H, Yong H, Takahashi T, Noda H, Oikawa K, Kamada H (1994) Ascorbic acid radical, superoxide, and hydroxyl radical are detected in reperfusion injury of rat liver using electron spin resonance spectroscopy. Arch Biochem Biophys 308:1–7

    Article  CAS  PubMed  Google Scholar 

  31. Troppmann C, Gillingham KJ, Gruessner RW, Dunn DL, Payne WD, Najarian JS, Matas AJ (1996) Delayed graft function in the absence of rejection has no long-term impact. A study of cadaver kidney recipients with good graft function at 1 year after transplantation. Transplantation 61:1331–1337

    CAS  PubMed  Google Scholar 

  32. Tsapas G, Magoula I, Paletas K, Concouris L (1983) Effect of peritoneal dialysis on plasma levels of ascorbic acid. Nephron 33:34–37

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Anaesthesia, Fourth Department of Surgery, Helsinki University Central Hospital, P.O. Box 263, 00029 HUS, Helsinki, Finland

    Karri Norio & Leena Lindgren

  2. Helsinki Bioenergetics Group, Programme for Structural Biology and Biophysics, Institute of Biotechnology, University of Helsinki, Helsinki, Finland

    Mårten Wikström

  3. Division of Transplantation, Fourth Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland

    Kaija Salmela & Lauri Kyllönen

Authors
  1. Karri Norio
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  2. Mårten Wikström
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  3. Kaija Salmela
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  4. Lauri Kyllönen
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  5. Leena Lindgren
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Correspondence to Karri Norio.

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Norio, K., Wikström, M., Salmela, K. et al. Ascorbic acid against reperfusion injury in human renal transplantation. Transpl Int 16, 578–583 (2003). https://doi.org/10.1007/s00147-003-0588-0

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  • DOI: https://doi.org/10.1007/s00147-003-0588-0

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