TREATMENT OF STEROID-RESISTANT ACUTE RENAL-ALLOGRAFT REJECTION

Steroid resistant acute rejection is an important cause of early graft loss and even if reversed by treatment it predisposes to chronic reje ction at a later stage. Predisposing factors to steroid resistant reje ction include HLA antibodies and young recipient age and on graft biop sy vascular damage is commonly seen. The most commonly used treatment is OKT3 which will result in reversal of the rejection in up to 90% of cases but longer term success is less satisfactory with one year graf t survival in these patients usually between 40% and 60%. Predictors o f a poor prognosis are the occurrence of rejection within a few days o f the transplant, at the other end of the time-scale acute rejection b eyond six months and thirdly when rejection is superimposed on delayed onset of transplant function, OKT3 is usually given in a dose of 5mg per day for 10 days but a lower dose and/or shorter course is often ap propriate, Cytokine release, predominantly TNF and IFN-gamma, may make OKT3 an unpleasant treatment for the patient but the typical symptoms of rigors, headache and vomiting can be largely prevented by high dos e steroids, In the longer term, the two most important complications a re opportunistic infections and malignant diseases and both correlate with the total OKT3 dose. The development of high titre murine antibod ies precludes a second course of OKT3 but such antibodies occur in les s than 10% of cases. Although prospective comparative studies are lack ing, it is a commonly held view that OKT3 is more effective in the rev ersal of steroid resistant rejection than ALG or ATG, Finally interest ing preliminary studies suggest that tacrolimus may have a useful role in the treatment of steroid resistant rejection.