A comparative analysis of results and morbidity in type I diabetics undergoing preemptive versus postdialysis combined pancreas-kidney transplantation.

Although combined pancreas-kidney transplantation (PKT) has become a valid treatment option for selected type I diabetics, the timing of PKT relative to the degree of nephropathy remains controversial. We analyzed results and morbidity in 30 type I diabetics undergoing PKT after starting dialysis (PKT:D) versus 31 type I diabetics undergoing PKT prior to dialysis (PKT:ND). The two groups were similar with the respect to age, duration and severity of diabetes, gender, race, preservation time, retransplants, sensitization, HLA-matching, and CMV status. The mean preoperative serum creatinine was higher in the PKT:D group (9.9 +/- 3.4 vs. 3.9 +/- 1.9 mg/dl PKT:ND, P < 0.01). All patients were managed with quadruple immunosuppression with OKT3 induction. Actuarial patient survival is 100% (PKT:D) and 96.8% (PKT:ND). Renal and pancreas allograft survival are 97% and 93%, respectively, in both groups. The incidence of rejection, infection, operative complications, reflux pancreatitis, and total hospital days was similar in both groups. Long-term renal and pancreas allograft function and quality of life were like-wise comparable. No adverse coagulation or immunologic effects were noted in the PKT:ND group. Rehabilitation potential favored the PKT:ND group. PKT can be performed safely and effectively in the absence of uremia. In selected type I diabetics with significant nephropathy, we believe that PKT is the best treatment option and need not be considered as preemptive, especially in view of increasing waiting times and the variable progressive nature of diabetic complications.

Recipient selection and evaluation for vascularized pancreas transplantation.

Vascularized pancreas transplantation (PT) is becoming an accepted therapy for selected type I diabetic patients. However, selection and evaluation criteria remain uncertain. In the last 3.5 years, we have interviewed 205 and evaluated 151 diabetic patients for PT. The degree of renal dysfunction (creatinine clearance below 45 ml/min) was used to select patients for combined pancreas-kidney transplantation (PKT) or solitary pancreas transplantation (PTA) (clearance above 70 ml/min). The cardiovascular evaluation (stress thallium study with liberal use of coronary angiography) was used to determine operative risk and provided the other major selection criterion. A total of 104 patients were selected as candidates for PT; 70 have undergone PKT with 98.6% patient survival (1 cardiovascular death), 97.1% kidney graft survival, and 94.2% pancreas graft survival. Thirty-three evaluated patients (24.1%) were not accepted as candidates for PT; 13 have undergone cadaveric kidney transplantation, 5 were placed on the kidney waiting list, and 9 have died. Criteria for PTA include 2 or more diabetic complications or hyperlabile diabetes. Patient (n = 12) and pancreas graft survival after PTA is 83.3 and 50%, respectively. Our conclusion is that a multidisciplinary approach was used for recipient selection for PT based on degree of nephropathy, cardiovascular risk, and presence of diabetic complications. Nearly 75% of diabetic patients evaluated were acceptable candidates for PT. Only 4 (3.8%) of these selected patients died while awaiting or undergoing PT, thus optimizing the use of scarce allograft resources and providing evidence for appropriate patient selection.

Reactive oxygen species and rat renal epithelial cells during hypoxia and reoxygenation.

To study the importance of oxygen free radical production by and injury to proximal tubule epithelial cells, an in vitro model was established. Rat renal proximal tubule epithelial cells in primary culture were subjected to normoxic conditions or 60 minutes of hypoxia and 30 minutes of reoxygenation. Under normoxic conditions, these cells produced superoxide radical, hydrogen peroxide, and hydroxyl radical. During hypoxia and reoxygenation, there was an increase in the production of these reactive oxygen species, detected in the extracellular medium, of 252, 226, and 45 percent, respectively. The production rate of superoxide radical was most markedly increased in the first five minutes of reoxygenation. Studies employing 2,7-dichlorofluorescein which fluoresces when oxidized by peroxides revealed a seven-fold increase in cellular fluorescence in cells studied after hypoxia and reoxygenation compared with control cells. That increased production of reactive oxygen species played a role in cellular injury was demonstrated by an increase in lipid peroxidation during hypoxia and reoxygenation, as well as substantial injury during hypoxia and reoxygenation which could be largely prevented by the addition of superoxide dismutase, catalase, dimethylthiourea, or deferoxamine to the cells. These studies demonstrate that proximal tubule epithelial cells produce reactive oxygen species in increased amounts during hypoxia and reoxygenation, and that these reactive oxygen species are injurious to the cells under these conditions.