Strategies for minimizing immunosuppression in kidney transplantation.
ABSTRACT Immunosuppression remains the cause of most morbidity following organ transplantation. However, its use is also responsible for the outstanding graft and patient survival rates commonplace in modern transplantation. Thus, the predominant challenge for transplant clinicians is to provide a level of immunosuppression that prevents graft rejection while preserving immunocompetence against environmental pathogens. This review will outline several strategies for minimizing or tailoring the use of immunosuppressive drugs. The arguments for various strategies will be based on clinical trial data rather than animal studies. A distinction will be made between conventional immunosuppressive drug reduction based on over-immunosuppression, and newer induction methods specifically designed to lessen the need for chronic immunosuppression. Based on the available data we suggest that most patients can be transplanted with less immunosuppression than is currently standard.
- American Journal of Transplantation 07/2003; 3(6):643-5. · 6.19 Impact Factor
Article: Humoral theory of transplantation.[show abstract] [hide abstract]
ABSTRACT: According to the humoral theory of transplantation, antibodies cause allograft rejection. Publications are cited showing that antibodies: (1). cause hyperacute kidney rejection, (2). lead to C4d deposits associated with early kidney graft failures, (3). are a good indicator of presensitization leading to early acute rejections, (4). were present in 96% of 826 patients who rejected a kidney graft, (5). are associated with chronic rejection in 33 studies of kidney, heart, lung and liver grafts, and (6). in three studies, appeared in the circulation BEFORE evidence of bronchiolitis obliterans in lung transplants, and BEFORE kidney rejection. In addition, a prospective cooperative study of 1629 patients in 24 centers demonstrated that antibodies foretold subsequent failures after a follow-up period of 6 months (p = 0.05). The specificity of antibodies detected in the serum of rejecting patients were often not donor specific, presumably because they were absorbed by the rejecting organ. If the humoral theory is accepted, even provisionally, transplanted patients who have antibodies could be treated with immunosuppression until the antibodies disappear to determine whether chronic rejection can be blocked. If successful, in patients who do not have antibodies, immunosuppression could be reduced until antibodies appear.American Journal of Transplantation 07/2003; 3(6):665-73. · 6.19 Impact Factor
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ABSTRACT: Campath-1H, an anti-CD52 monoclonal antibody, was used as induction therapy (40 mg i.v. total dose) in 29 primary human renal transplants, and the patients were maintained on rapamycin monotherapy (levels 8-15 ng/mL) post-transplant. Campath-1H profoundly depletes lymphocytes long-term and more transiently depletes B cells and monocytes. All patients are alive and well at 3-29 months of follow up. One graft was lost because of rejection. There have been no systemic infections and no malignancies. Eight of 29 patients have experienced rejection, which was successfully treated in seven of eight patients. Five of these patients had pathological evidence of a humoral component of their rejection. Seven of the 29 patients were converted to standard triple therapy on account of rejection. Rapamycin was generally well tolerated in that there were no significant wound-healing problems; two lymphoceles required surgical drainage; and most patients were treated with a lipid-lowering agent. Flow crossmatch testing post-transplant revealed evidence of alloantibody in two patients tested with previous combined cellular and humoral rejection. Biopsies have shown no chronic allograft nephropathy to date. In view of the relatively high incidence of early humoral rejection, we plan to modify the immunosuppressive regimen in subsequent pilot studies. This clinical trial provides insight into the use of Campath-1H induction in combination with rapamycin maintenance monotherapy.American Journal of Transplantation 07/2003; 3(6):722-30. · 6.19 Impact Factor