Commentary on pretransplantation: removing immunologic barriers

Abstract

G iven a rather static number of deceased organ donors in the United States, finding enough cadaveric organs to meet the ever-increasing demand for transplantation seems unlikely in the foreseeable future. Already, kidneys from living donors have increased 3-fold over the last decade, accounting for almost half of all renal allografts in the United States in 2002.1 As many as 15% to 20% of those on the waiting list may have potential live donors that were not used because of major histocompatibility complex presensitization or ABO incompatibility. It now appears that these previously insurmountable barriers may actually be amenable to novel therapies that reduce their impact. In the first study, Sonnenday and colleagues report on 33 patients who received successful kidney transplants from live donors at The Johns Hopkins Hospital despite presensitization. With careful immunologic monitoring, aggressive preconditioning, and a high level of posttransplant surveillance, success rates were quite high. Even recipients who experienced antibody-mediated rejection ultimately maintained excellent allograft function over 12 to 18 months. In the second study (randomized and placebo controlled), Jordan and colleagues used highdose intravenous immunoglobulin to successfully desensitize transplant candidates with a mean panel reactive antibody level of 81%. Thirty-seven percent of these patients received subsequent transplants, with excellent outcomes. In the third study, Tanabe and colleagues continue to refine their experience with ABO-incompatible transplants in Tokyo, achieving long-term graft survival in almost all cases with a protocol that includes plasmapheresis, intravenous immunoglobulin, splenectomy, and pretransplant immunosuppression. Although more costly to perform than a standard transplant, successful engraftment after desensitization is still substantially less expensive over time than remaining on dialysis. These new approaches reflect the impact of several recent advances. First, better laboratory techniques enable easier identification and quantification of ABO and specific anti-HLA antibody.2 Second, greater precision in histologic diagnosis of antibody-mediated events within the allograft is now possible because of advances that include C4d staining.3 Third, availability of effective immunosuppression with tacrolimus, mycophenolate mofetil, and corticosteroids appears to suppress antibody production after transplantation.4 The ongoing organ shortage almost mandates increasing application of these protocols in coming years if we are to increase availability of kidney transplantation to those who have no other alternative to a prolonged wait on dialysis.