Muromonab-CD3 and antithymocyte globulin in renal transplantation

To review the recently published medical literature for the practical and efficient use of muromonab-CD3 (OKT-3) and antithymocyte globulin (ATG) in renal transplantation.

MEDLINE and EMBASE were searched (1985-February 1996). Key words used were antithymocyte globulin (ATG, Atgam), muromonab-CD3 (OKT-3, Orthoclone), and kidney transplantation. Thereafter, the search was restricted to English-language articles, clinical trials, and human studies.

The search was reviewed for articles of interest, and pertinent references from these articles were further reviewed to supplement the initial search. The review focused on antibody therapy as induction and/or rejection therapy in renal transplantation.

Although ATG and OKT-3 are effective in delaying and reducing the occurrence of acute rejection, their impact on long-term graft survival has not been established. Improved graft survival has, however, been demonstrated in patients at high risk for rejection. These risks are described in the review. As first-line or steroid-resistant rejection therapy, ATG and OKT-3 have proven efficacious. Some studies have shown improved graft survival with OKT-3. Although serious infections may occur, OKT-3 has been shown to be effective in reversing rejections resistant to both steroids and ATG. Therefore, reserving OKT-3 for steroid- or ATG-resistant rejections may be preferred over the first-line use of OKT-3, which is limited by the development of antimurine antibodies with subsequent uses. However, the benefits of first-line antibody therapy may outweigh the risks of developing these antibodies in patients for whom high-dose steroids may not be the most appropriate treatment. Other factors that need to be considered are adverse effects, which appear to be lower with ATG, cost, and total hospital charges. The accuracy of treatment outcomes analysis among these studies is limited by variations in the immunosuppressive regimens of the study centers, doses of concomitant therapies, use of prophylactic antibiotics, and time to follow-up.

While important benefits are realized from using antibody therapies in renal transplantation, their use is often associated with excess immunosuppression and increased treatment costs. Despite encouraging results from published trials, questions regarding the extent of their prophylactic use and impact on long-term outcomes need to be answered. The current literature contains no prospective, controlled, randomized comparisons of OKT-3 and ATG with standardized regimens of conventional immunosuppressive agents and antirejection protocols. The majority of studies use OKT-3 as part of the treatment protocol. Well-designed studies using ATG are lacking. Further research is needed to refine treatment protocols for ATG and OKT-3 to determine the optimal timing and dosing for these agents.