Factors contributing for improved graft survival in recipients of kidney transplants

We analyzed the survival results of 300 consecutive kidney transplants (TXs) performed at Hennepin County Medical Center, Minneapolis, Minnesota, between March 1965 and April 1980. The graft survival result were compared between three sequential time periods, each comprising 100 renal TXs. The proportion of live donor TXs decreased from 27% in period 1 to 16% in period 2 and 5% in period 3, while the number of older patients, diabetic and multiple TX patients increased steadily. A comprehensive patient care scheme utilizing clinical protocols was developed in period 2 and carried out effectively in period 3. The Cox multivariate regression models used in this analysis allowed us to assess the influence of each variable on the graft survival results, while the effects of all others were held constant. Among the nondiabetic patients who received antilymphocyte globulin, the 1 and 5 year graft survival rates were 59.7 and 38.8% in period 1, 85.3 and 74.3% in period 2, 90.4 and 83.1% in period 3 (periods 1 versus 2: P = 0.008, periods 1 versus 3: P less than 0.0001). This improvement in graft survival was independent of the effects of the following variables, that is, the recipient's age, donor source, prior dialysis, co-existing medical problems, splenectomy, previous TXs, blood transfusions, cytotoxic antibodies, cold ischemia time, HLA mismatches, and post-TX acute tubular necrosis. Our observations indicate that reduced immunosuppression, frequent use of biopsy specimens and comprehensive patient care, played an important role in minimizing the loss of renal transplants in the later time periods and contributed indirectly for the improved graft survival results of our institution.     

Achieving adequate cyclosporine exposure in liver transplant recipients: a novel strategy for monitoring and dosing using intravenous therapy.

It has been demonstrated that achieving therapeutic levels of cyclosporine (CsA) exposure in the first days posttransplant is critical for effective prevention of rejection. In patients receiving oral CsA, it has been shown that C(2)-monitoring is superior to trough (trough level [C(0)]) measurement. Intravenous administration may overcome the problem of CsA absorption dysfunction seen in some patients. Currently, little evidence is available concerning CsA exposure after intravenous application. Twenty de novo liver transplant recipients were given twice-daily 4-hour infusions of intravenous CsA, with full pharmacokinetic profiles undertaken during the first postoperative week. The greatest CsA exposure occurred during the period 2 to 4 hours after the start of infusion. The correlation between C(0) and area under the curve (AUC(0-12)) was r(2) = 0.18; the correlation between C(2) and AUC(0-12) was r(2) = 0.82. The best 2-point predictive model included both C(2) and C(4) (r(2) = 0.90). There was a poor correlation between CsA dose per kilogram of body weight and AUC(0-12) (r(2) = 0.19); total CsA dose also showed a weak relationship to exposure (r(2) = 0.37). When patients were divided according to initial or delayed graft function, there was good correlation between total CsA dose and AUC(0-12) (initial function, r(2) = 0.71; delayed function, r(2) = 0.86). In conclusion, previous discouraging results with intravenous CsA in liver transplant patients may have been due to a limited understanding of CsA pharmacokinetics. Our results show that C(2)-monitoring during 4 hour infusion provides a reliable indication of CsA exposure. Calculation of starting dose based on initial graft function is more precise than use of body weight. Using C(2)-monitoring to individualize dosing and function-based calculations of starting dose could be expected to improve clinical outcomes in patients receiving intravenous CsA.     

Quality of life in diabetic recipients of kidney transplants is better with the addition of the pancreas

The present study is an evaluation of the quality of life of 32 patients following successful pancreatic transplantation. These patients were studied at from 6 months to 5 years post-transplantation. Over one-half of them were beyond the 21/2-yr mark. A questionnaire was developed that focused on symptoms of neuropathy, enteropathy, and retinopathy. All of the patients evaluated had completely normal carbohydrate metabolism, as evidenced by normal fasting blood sugars and hemoglobin A1C levels. Twenty-one of the 32 patients had symptomatic neuropathy pre-operatively, and 11 of these reported substantial subjective improvement. Eight remained unchanged and 2 became worse. Twenty-four patients had symptoms of enteropathy and 23 noted improvement post-transplantation. Retinopathy symptoms were not improved, but there was a suggestion that after 3 or 31/2 yr progression did not occur as rapidly as earlier. Virtually all of the patients had mood improvements and considerably less fatigue. We have determined that the risk of the procedure when receiving simultaneous renal and pancreas grafts is not significantly greater than that associated with a kidney transplant alone. Patients who are not uremic, either those with a successful kidney graft or those preuremic patients, are better candidates if symptoms are present. The risk of immunosuppression is insignificant in those patients who already have a successful renal transplant and are already on immunosuppressant drugs. Pancreatic transplantation can substantially improve the quality of life in diabetic patients, and should be considered as a therapeutic measure.     

Re‐transplants compared to primary kidney transplants recipients: a mate kidney paired analysis of the OPTN/UNOS database

Outcomes of kidney re‐transplant recipients (RTR) were compared to primary recipients (FTR) from paired donor kidneys. Organ Procurement and Transplantation Network (OPTN) database was used to identify deceased donors (n = 6266) who donated one kidney to an RTR and the mate kidney to an FTR between January 2000 to December 2010. As compared to FTR, RTR were younger (45 vs. 52 yr, p < 0.001) and had higher proportion of plasma reactive antibody >80 (25% vs 7%, p < 0.001). There were higher 0 mismatches in RTR (19% vs. 16%, p < 0.001). There were more pre‐emptive transplants in RTR (24% vs. 21%, p = 0.002). Delayed graft function (28% vs. 25%, p = 0.007) was higher in RTR. Patient survival was similar in FTR and RTR groups at one, three, and five yr (95.7%, 90.2%, and 82.5% vs. 95.2%, 89.8% and 82.7%). Allograft survival rates were higher in FTR group compared to RTR group at one, three, and five yr (91.1%, 82.4%, and 70.9% vs. 87.8%, 77.4%, and 66.1% p < 0.001). Death‐censored allograft survival rates were higher in FTR group at one, three, and five yr (91.3%, 82.7% and 71.4% vs. 88%, 77.7% and 66.5% p < 0.001). In today's era of modern immunosuppression, graft survival in RTR has improved but remains inferior to FTR when controlling for donor factors.     

Sinoatrial node dysfunction in recipients of domino heart transplants: complication of a surgical harvesting technique.

Two of six domino transplantations performed at our institution required permanent pacemaker implantation as a result of persistent sinoatrial node dysfunction and symptomatic nodal rhythm. Retrospective analysis of several potential etiologic factors showed that the only obvious difference between these two patients and the remaining four domino transplant recipients without this complication was the technique used during harvesting of the cardiac graft. The hearts from the two patients with sinoatrial node dysfunction were harvested using a "right atrial cuff preservation" technique, and the hearts of the remaining four patients were harvested with a standard bicaval division technique. Based on this experience, we think that this right atrial cuff preservation harvesting technique carries a potential risk for sinoatrial node damage, and we do not recommend its use for domino transplantation.     

Dramatic improvement in the success rate for renal transplants in diabetic recipients with donor-specific transfusions

The chance of achieving successful kidney transplants in diabetic patients was previously limited because few of them had optimally-matched (2-haplotype) related donors. Hence, transplants were usually not carried out until renal failure had already occurred. The application of donor-specific transfusions (DSTs) prior to transplantation to poorly matched donor-recipient pairs (1-haplotype) has been associated with a high success rate for type-I diabetic recipients in our center. The rate of graft survival for 35 consecutive transplants in this category was 88%, 80%, and 73% at 1, 2, and 5 years, respectively. Furthermore, the rate of patient survival was 94%, 90%, and 90% at 1, 2, and 5 years. These patient and graft survival data were without significant difference when compared with the corresponding data for 142 optimally-matched (2-haplotype) related transplants performed without DSTs for nondiabetic recipients, and also when compared with the corresponding data for 130 poorly matched (1 or 0-haplotype) related transplants involving nondiabetic recipients who were prepared for transplantation with DSTs. These good results with DSTs in diabetic recipients emphasize that earlier transplantation utilizing poorly matched related donors should be seriously considered for diabetic patients even before the onset of renal failure, as long as the transplants are carried out in association with DSTs.