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 mumol/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 mumol/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.