Tolerogenic immunosuppression for organ transplantation.

BACKGROUND: Insight into the mechanisms of organ engraftment and acquired tolerance has made it possible to facilitate these mechanisms, by tailoring the timing and dosage of immunosuppression in accordance with two therapeutic principles: recipient pretreatment, and minimum use of post-transplant immunosuppression. We aimed to apply these principles in recipients of renal and extrarenal organ transplants. METHODS: 82 patients awaiting kidney, liver, pancreas, or intestinal transplantation were pretreated with about 5 mg/kg of a broadly reacting rabbit antithymocyte globulin during several hours. Post-transplant immunosuppression was restricted to tacrolimus unless additional drugs were needed to treat breakthrough rejection. After 4 months, patients on tacrolimus monotherapy were considered for dose-spacing to every other day or longer intervals. FINDINGS: We frequently saw evidence of immune activation in graft biopsy samples, but unless this was associated with graft dysfunction or serious immune destruction, treatment usually was not intensified. Immunosuppression-related morbidity was virtually eliminated. 78 (95%) of 82 patients survived at 1 year and at 13-18 months. Graft survival was 73 (89%) of 82 at 1 year and 72 (88%) of 82 at 13-18 months. Of the 72 recipients with surviving grafts, 43 are on spaced doses of tacrolimus monotherapy: every other day (n=6), three times per week (11), twice per week (15), or once per week (11). INTERPRETATION: The striking ability to wean immunosuppression in these recipients indicates variable induction of tolerance. The simple therapeutic principles are neither drug-specific nor organ-specific. Systematic application of these principles should allow improvements in quality of life and long-term survival after organ transplantation.

Hemorrhagic complications of enoxaparin and aspirin in patients with kidney transplants.

STUDY OBJECTIVE: To evaluate the frequency of early posttransplant hemorrhagic complications in patients with kidney and kidney-pancreas transplants who received thromboprophylaxis with enoxaparin and aspirin. DESIGN: Retrospective chart review. SETTING: University-based tertiary care center. PATIENTS: Thirteen patients who had received enoxaparin within 10 days of kidney or kidney-pancreas transplantation. INTERVENTION: Medical records were reviewed, and data from patients who had received low-dose aspirin 81 mg once/day and enoxaparin within 10 days of transplantation were collected. MEASUREMENTS AND MAIN RESULTS: Major bleeding events were defined as intracranial or retroperitoneal bleeding, or a decrease in hemoglobin of greater than 2 g/dl that was confirmed on repeat evaluation. Nine (69%) of the 13 patients had confirmed major bleeding events and required blood transfusions. Six of the nine patients had elevated serum creatinine levels. CONCLUSION: The combination of enoxaparin and low-dose aspirin early after kidney or kidney-pancreas transplantation was associated with a high frequency of hemorrhagic events. Further evaluation is needed to determine the safety of enoxaparin in combination with aspirin after transplantation.