Prognostic significance of free radicals: mediated injury occurring in the kidney donor

Background. Brain death is associated with hemodynamic disturbances in systemic circulation and metabolic storm, and, thus, free radical-mediated injury to donor tissues was hypothesized. An assessment of oxidative stress in the donor and its effect on posttransplant kidney graft function comprised the scope of the study. Methods. A prospective study was performed in 27 donors and 50 kidney transplant recipients. Sera from 27 brain-dead organ donors and preservation media were tested for malondialdehyde (MDA) and for total antioxidant status (TAS). Kidneys were preserved in University of Wisconsin-gluconate solution with machine perfusion. Mean ischemia time was 36.7±8 hours. Organs were transplanted to recipients on the Polish National Waiting List and posttransplant kidney function was monitored periodically. Posttransplant delayed graft function (DF) was diagnosed when a patient required at least one dialysis within first week after transplantation. Acute rejection was diagnosed clinically and confirmed with fine-needle biopsy if necessary. Results. Thirty-two recipients had immediate graft function (IF), and 18 suffered from DF. MDA level in preservation solution at the end of machine perfusion was significantly higher in the DF group (52.6±31 vs. 25.3±19 &mgr;mol/L) whereas donor TAS activity was lower (1.14±0.2 vs. 0.97±0.3 mmol/mL). Patients who suffered from acute rejection received kidneys from donors with significantly higher serum MDA (66±73 &mgr;mol/ml vs. 23±49 for patients without rejection). Serum creatinine 12 to 48 months after transplantation correlated to donor- and preservation-solution MDA (P <0.006). Conclusions. Free-radical mediated injury occurring in the donor and during preservation is strictly correlated with immediate and long-term kidney function. It may also cause grafts to be prone to acute rejection.

[1]  R. Jackson,et al.  Reactive species mechanisms of cellular hypoxia-reoxygenation injury. , 2002, American journal of physiology. Cell physiology.

[2]  P. V. van Heerden,et al.  The Physiological Changes Associated with Brain Death-Current Concepts and Implications for Treatment of the Brain Dead Organ Donor , 1995, Anaesthesia and intensive care.

[3]  P. Blankestijn,et al.  Cardiovascular risk factors in renal transplant patients: cyclosporin A versus tacrolimus. , 2001, Journal of the American Society of Nephrology : JASN.

[4]  B. Jaques,et al.  The impact of late acute rejection after cadaveric kidney transplantation , 2001, Clinical transplantation.

[5]  R. Willers,et al.  Risk factors for delayed graft function after renal transplantation and their significance for long-term clinical outcome , 2002, Transplant international : official journal of the European Society for Organ Transplantation.

[6]  J. Ringers,et al.  Increased immunogenicity and cause of graft loss of old donor kidneys. , 2001, Journal of the American Society of Nephrology : JASN.

[7]  R. Hetzer,et al.  Procalcitonin, A Donor-Specific Predictor of Early Graft Failure-Related Mortality After Heart Transplantation , 2001, Circulation.

[8]  L. Pączek,et al.  Six-year experience in continuous hypothermic pulsatile perfusion kidney preservation. , 2001, Transplantation proceedings.

[9]  B. Hoffman,et al.  Coordination environment for the type 3 copper center of tree laccase and CuB of cytochrome c oxidase as determined by electron nuclear double resonance. , 1983, The Journal of biological chemistry.

[10]  T. Shimizu,et al.  Time-dependent risk factors influencing the long-term outcome in living renal allografts: donor age is a crucial risk factor for long-term graft survival more than 5 years after transplantation. , 2001, Transplantation.

[11]  G. Opelz Very short ischaemia is not the answer. , 2002, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[12]  M. Wilhelm,et al.  Activation of inflammatory mediators in rat renal isografts by donor brain death. , 2000, Transplantation.

[13]  A. Jardine,et al.  Early graft function and patient survival following cadaveric renal transplantation. , 1999, Kidney international.

[14]  D. Dunn,et al.  Risk factors for prolonged hospitalization after kidney transplants. , 1997, Clinical transplantation.

[15]  L. Pączek,et al.  Does "second warm ischemia time" play a role in kidney allograft function? , 1999, Transplantation proceedings.

[16]  A. Khaghani,et al.  Activation of Apoptotic and Inflammatory Pathways in Dysfunctional Donor Hearts1 , 2000, Transplantation.

[17]  A. Jardine,et al.  The impact of delayed graft function on the long-term outcome of renal transplantation. , 2002, Journal of nephrology.

[18]  F. Kajiya,et al.  Endothelial dysfunction in ischemic acute renal failure: rescue by transplanted endothelial cells. , 2002, American journal of physiology. Renal physiology.

[19]  J. Ehrich,et al.  Randomized trial of tacrolimus versus cyclosporin microemulsion in renal transplantation , 2002, Pediatric Nephrology.

[20]  P. Živný,et al.  The role of cytokines and antioxidant status in graft quality prediction. , 1999, Transplantation proceedings.

[21]  L. Pączek,et al.  Storage by continuous hypothermic perfusion for kidney harvested from hemodynamically unstable donors. , 1996, Transplantation proceedings.

[22]  R. Latimer,et al.  Management of donors for heart and heart–lung transplantation , 1990, Anaesthesia.

[23]  F. Belzer Evaluation of preservation of the intra-abdominal organs. , 1993, Transplantation proceedings.

[24]  N. Sims,et al.  Mitochondrial contributions to tissue damage in stroke , 2002, Neurochemistry International.

[25]  D. Gjertson Impact of delayed graft function and acute rejection on kidney graft survival. , 2000, Clinical transplants.

[26]  C. Burlet,et al.  Changes in hemodynamic and metabolic parameters following induced brain death in the pig. , 1994, Transplantation.

[27]  R. Sorelle United Network for Organ Sharing. , 1997, Circulation.