Mycophenolate Mofetil Study.

Abstract

The Tricontinental Mycophenolate Mofetil Study Group (1) reported that the addition of mycophenolate mofetil, the standard immunosuppressive regimen in renal cadaveric allografts, reduces the incidence of rejection in the first 6 months from 48% to 29%; the relative risk of acute rejection is reduced 39%, with 95% confidence limits of 30-60%. However, making the reasonable assumption that unbiopsied acute rejections are grade I, then this reduction is entirely accounted for by the decrease in grade I rejections because there is no reduction in grade II and III rejections. These grades have an incidence of 8.3% (28/309) in the treatment group and 8.4% (14/152) in the control group. This yields a P-value of <0.99, relative risk reduction of 1%, and range of 0.53-1.82. At the same time, there is no change in the 6-month acute rejection graft loss rate. Thus, demonstrated benefit from this new agent is a reduction in the incidence of mild rejection and no effect on 1-year graft survival, which is not an impetus to the use of this agent. Instead, the major argument for is use comes from a potential benefit-a reduction in chronic rejection because of a reduction in acute rejection. However, while these forms of rejection correlate, their is evidence currently suggesting that the reduction is not cause and effect. This means that preventing acute rejection, especially acute cellular rejection, may not prevent chronic vascular rejection: (a) Terasaki et al. (2) have shown that acute rejection impacts long-term kidney graft survival only by improving the 1-year survival rate. Graft survival rates thereafter were similar in those with and without previous rejection. The tricontinental study showed no difference between the three arms at the end of 1 year. (b) Pregraft transfusion reduces the incidence of acute rejection, but does not increase long-term graft survival. (c) Similarly, cyclosporine increases short-term but not long-term survival. (d) The incidence of acute rejection is high (3-8) in two-haplotype-identical grafts, but chronic rejection is virtually nonexistent (3). (e) van Saase et al. (9) show that in cadaveric grafts, acute cellular rejection is not predictive of chronic rejection and only the acute vascular form is so predictive. (f) More than 30 years ago, Merrill (10) indicated that “acute vasculitis” in a renal graft was unconnected to acute rejection but did relate to chronic graft loss. The role of mycophenolate mofetil in chronic rejection might be defined more quickly by using it in early chronic rejection after the linear logarithmic slope of the chronic renal failure is established to determine whether it decelerates the slope. Furthermore, if delayed graft function predicts late graft failure, mycophenolate might prove to be a hazard. It has a 93.5% probability of doing so, a relative risk of 57%, and 95% confidence limits of 3-155%. M. Baltzan1; A. Shoker; R. Baltzan Baltzan Clinic; Saskatoon, Saskatchewan, S7K 1M5 Canada