Mycophenolate Mofetil Improves Long Term Graft Survival Following Renal Transplantation in Patients Experiencing Delayed Graft Function

Abstract

217 Delayed graft function (DGF) has been demonstrated to have a significant deleterious impact on long term graft survival. In fact, several studies have indicated it is second only to acute rejection in this regard. Additional investigations have suggested an immunologic basis for this decreased survival. Also, the coexistence of DGF and acute rejection has portended extremely poor graft survival. Three large prospective, randomized, double blind, controlled trials demonstrated a significant reduction in the frequency and severity of rejection episodes in renal transplant recipients treated with mycophenolate mofetil (MMF), (CellCept®, Hoffman- LaRoche), compared to those receiving azathioprine (AZA) or placebo (all in combination with cyclosporine and corticosteroids). The current study was undertaken to investigate any potential benefit of MMF in the setting of DGF, defined as the need for dialysis in the first week post-transplant. The incidence of DGF in each of the studies (∼10-30%) was too low to allow statistical conclusions within each study. As two of the studies (USA and Tri-Continental) had similar maintenance immunosuppressive protocols, a pooled risk factor analysis of graft and patient survival from these two studies was performed. DGF occurred in 48 of 326 patients in the combined AZA group and 67 of 336 and 65 of 330 patients in the MMF 2gm/day and MMF 3gm/day groups respectively. Regardless of treatment, DGF was a significant risk factor for both patient (p=0.0011) and graft (p=0.0001) survival. In patients experiencing DGF, graft survival was significantly improved in the MMF 2gm/day group vs. the AZA group (p=0.0370): incidence of graft loss or patient death at 3 years was 44% in the AZA group, 24% in the MMF 2gm/day group and 35% in the MMF 3gm/day group. Most graft losses were due to rejection. Conclusion: Improved graft survival was obtained in MMF treated patients with DGF (especially in the 2gm/day group).