DECREASED ACUTE KIDNEY TRANSPLANT REJECTION IS ASSOCIATED WITH DECREASED CHRONIC REJECTION

Abstract

309 With current immunosuppressive protocols, kidney graft loss is rarely due to acute rejection (AR), so the focus of studies has shifted to chronic rejection (CR). Yet AR is the major risk factor for development of biopsy-proven CR. However, until now, no study had demonstrated that a decrease in AR leads to a decrease in CR. We studied 2 eras to determine whether the recent decrease in the rate of AR was associated with decreased CR and increased graft half-life (t 1/2) (the time it takes for 1/2 the grafts functioning at 1 year to fail). Between 1984-1988, we did 493 primary kidney transplants in adults (240 living donor [LD]; 253 cadaver donor [CAD]); between 1991-1995, 563 (316 LD, 247 CAD). Immunosuppressive protocols during both eras included prednisone, azathioprine, and cyclosporine (CSA); the major difference was a more aggressive CSA dosing policy in the 2nd era, both for maintenance and after a rejection episode. Between 1991-1995, mean CSA level (±SE) (by HPLC) was significantly higher (vs. between 1984-1988) (p<.05) at 1 month (214±7 vs. 194±7), 2 mos (194±7 vs. 175±6), 6 mos (156±4 vs. 133±5), and 1 yr (124±4 vs. 101±4 Between 1991-95, more recipients were AR-free and fewer had ≥1 AR episodes (p=.004 for CAD; .06 for LD) (Table).TableThis decreased rate of AR was associated with a significantly decreased incidence of biopsy-proven CR (log rank) (Figures) (p=.0001 CAD; .08 LD). As a result, t 1/2 (±SE) increased in CAD recipients from 9.3±.9 to 11.2±1.7 yrs, and in LD recipients from 16±1.7 to 21±4 years.FigureOur study shows that decreased AR is associated with decreased CR and increased t 1/2. The data suggests that further decreasing the rate of AR by using the new immunosuppressive agents should decrease CR and increase graft survival.