Angiotensin converting enzyme inhibition in chronic allograft nephropathy

Background. Although angiotensin-converting enzyme inhibition has been shown to slow progression of chronic allograft nephropathy in animal models, no studies have examined its efficacy in humans. Methods. We retrospectively analyzed 63 patients with biopsy-proven chronic allograft nephropathy who had greater than or equal to6 months dialysis-free follow-up at our institution. A total of 32 patients treated for greater than or equal to6 consecutive months with angiotensin-converting enzyme inhibition and/or angiotensin-receptor blocker (ARB) therapy (group 1) were compared with 31 patients not on these agents (group 2). Results. Except for a higher incidence of hypertension (100 vs. 78%, P=0.005) in group 1, there were no significant differences in baseline clinical characteristics at time of biopsy. With a mean follow-up time of 27 months in both groups, 6 of 32 (19%) group 1 patients vs. 12 of 31 (39%) group 2 reached the primary endpoint of greater than or equal to50% increase in serum creatinine (P=0.10). Mean time to primary endpoint was 46.6 months in group 1 vs. 32.7 months in group 2 (P=0.07). Three of 32 (9%) of group 1 patients vs. 8 of 31 (26%) of group 2 returned to dialysis during this time (P = 0.11). Significantly fewer patients in group 1 reached the combined secondary endpoint of allograft failure or death (9.4 vs. 35.5%, P=0.01); in addition, group 1 had a longer mean time to this endpoint (51.2 vs. 37.6 months, P=0.03). On multivariate analysis, the only predictor of progression to primary endpoint was a high baseline serum creatinine (P=0.02). No significant differences in hyperkalemia or anemia were found between the two groups. Conclusions. Angiotensin-converting enzyme inhibition/angiotensin-receptor blocker therapy is well tolerated in renal allograft recipients with chronic allograft nephropathy. It is associated with a trend of slowing renal insufficiency as well as a significant survival benefit in the combined endpoint of allograft failure or death.