JOURNAL ARTICLE
REVIEW

[Immunosuppressive therapy in renal transplantation]

H Nakamura
Nihon Hinyōkika Gakkai Zasshi. the Japanese Journal of Urology 1993, 84 (8): 1359-84
8411796
In 1960, the beneficial effect on allograft survival of 6-mercaptopurine (6-MP) was demonstrated. In 1961, azathioprine, a less toxic derivative of 6-MP, was synthesized and soon became the main form of maintenance therapy. Around the same time, clinical studies of the effects of corticosteroids on the immune system were being conducted and successful reversal of rejection with cortisone was recognized. Subsequently, steroids were added to azathioprine and this regimen constituted maintenance immunosuppressive therapy in most centers for over 20 years. However, these first generation immunosuppressive medications are the cause of the majority of complications following renal transplantation. Both azathioprine and steroids effect nearly all immunologic and inflammatory responses and may predispose to infection and certain malignant diseases. Despite refinement in the use of these agents with improved patient survival, little improvement in graft survival was appreciated. The second generation immunosuppressive agents, antilymphocyte globulin (ALG), emerged in the form of polyclonal antibodies derived from xenotypic antisera and directed against the entire cellular response. Unfortunately, many limitations have been encountered with respect to the administration of ALG. Cyclosporine A is more specific and attacks a subset of the lymphocyte population, the T helper lymphocytes. When cyclosporine A is used in combination with prednisone, the immunologic cycle that causes rejection is interrupted twice by virtue of the fact that prednisone prevents the production of IL-1 by macrophages and cyclosporine A with the production of lymphokines, especially IL-2 (T-cell growth factor). Although cyclosporine A is at present better immunosuppressive drug to azathioprine, it is not without a number of side-effects. Nephrotoxicity, however, is the most worrying complication in patients receiving cyclosporine A. Of most importance to the urologist, however, is the interaction with cyclosporine A by many of the drugs used to treat various urologic infections. The advent of hybridoma technology which has become so important to the urologic oncologist has also impacted upon transplantation and resulted in the development of a new generation of antilymphocyte antibodies. The bulk of clinical experience has been obtained with OKT3, a monoclonal antibody directed against the T3 antigen complex found on all T-lymphocytes. A large multi-center experience has showed the remarkable efficacy of OKT3 in providing rapid depletion of peripheral blood T cell levels and reversal of established rejection not responded to conventional high-dose steroid therapy and in reducing the frequency and delay of the onset of rejection reactions.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Trending Papers

Remove bar
Read by QxMD icon Read
8411796
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"