Effect of increasing baseline immunosuppression on the prevalence of clinical and subclinical rejection: A pilot study

This group has reported that treatment of subclinical rejection in the firs t 3 mo posttransplant with corticosteroids decreases late clinical rejectio ns and improves graft function at 2 yr in renal transplant recipients. The current study was performed to determine whether an increase in baseline im munosuppression would decrease the prevalence of early subclinical rejectio ns, as well as the incidence of early and late clinical rejections. Patient s received mycophenolate mofetil (MMF) and Neoral cyclosporin A (CsA) postt ransplant (n = 29), of which 17 underwent protocol biopsies at months 1, 2, 3, and 6 (Neoral + MMF Protocol Biopsy [Bx]), while 12 declined protocol b iopsies (Neoral + MMF Control). These individuals were compared with 72 his torical control patients treated with Sandimmune CsA and Imuran, of which 3 6 had undergone protocol biopsies at months 1, 2, 3, and 6 (Sandimmune + Az athioprine [AZA] Protocol Ex), and 36 had a protocol biopsy at month 6 (San dimmune + AZA Control). Baseline immunosuppression with Neoral + MMF decrea sed the incidence of early clinical rejections (0 to 3 mo) and cumulative c orticosteroid exposure, but had no impact on the prevalence of early subcli nical rejection. Moreover, to maximally decrease the risk of developing lat e clinical rejections (months 7 to 12) in Neoral + MMF patients required th at protocol biopsies be done and that subclinical rejection be treated. The paradoxical finding of recent clinical trials that a reduction in acute cl inical rejection has not improved long-term graft outcome may be explained in part by the failure to control subclinical rejection.