Tacrolimus: A Step Closer to Control of Graft Rejection A controlled trial with two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less, n approximately 30 years, organ transplantation has become almost too successful. A shortage of organs has prompted renewed debate about whether people should register their unwillingness to be a donor, all others being presumed to consent. On the research front the same scarcity has in part led to experiments with organs from pigs (genetically modified or not) for donor material or as temporary support for patients in organ failure. Both proposals are controversial, and the latter has been complicated lately by concerns about the risk of transfer of porcine endogenous retroviruses. Toxicity is an important measure in trials such as this one in renal patients (paper #3); the efficacy endpoints are survival of patient and of graft (the latter reflecting cases where the graft has been irreversibly rejected or removed for other reasons but the patient survives by returning to dialysis or having a repeat transplant) and the frequency of rejection. Neither patient survival nor graft survival were significantly different between the tacrolimus and the cyclosporine groups, but acute rejection demanding immediate treatment (e.g., with anti-lymphocyte globulin) was significantly more common in the cyclosporine group (46.4% versus 30.7%). Diabetes as a post-transplant complication was five times as common with tacrolimus (19.9% versus 4.0%), and there was also more neurotoxicity with this drug. On the other hand, patients on the newer agent seemed to be spared the serum lipid abnormalities with which cyclosporine is associated.
