The Effect of Mycophenolate Mofetil on Chronic Rejection after Renal Transplantation

Park, Jung Hee; Park, Joo Hyun; Kim, Hyung Keun; Yang, Chul Woo; Kim, Yong Soo; Moon, In sung; Koh, Yong Bok; Bang, Byung Kee

Abstract

BACKGROUND: Although chronic rejection remains the leading cause of late graft failure, the pathophysiology of the phenomena is not completely understood and no specific treatment is available. The new immunosuppressive agent, mycopheonolate mofetil (MMF), has been effective for treatment of acute rejection and acute refractory rejection after renal transplantation. MMF has been thought to have potential effects on chronic rejection because it can inhibit arterial smooth muscle cell proliferation and antibody synthesis and also inhibit lymphocytes recruitment to the inflammatory site by diminishing activity of adhesion molecule. But there have been only a few reports about its effect on chronic rejection.
METHODS
Thirty-three renal transplant patients with chronic rejection which was clinically suspected or biopsy proven were enrolled in this study. Patients who have taken azathioprine as one of their immunosuppressive regimen discontinued azathioprine and all patients added MMF to their immunosuppresants. We reduced cyclosporine doses on some patients according to their cyclosporine blood level. Before the change of immunosuppresive regimen, the mean serum creatinine was 1.94+/- 0.37 mg/dl. The mean follow up period after the change of immunosuppresants was 6.57+/- 2.1 months.
RESULTS
After this MMF trial, mean serum creatinine was significantly decreased during the follow up period as compared with the pretreatment value (at months 1, 1.82 +/-0.33 mg/dl, at months 3, 1.76 +/-0.38 mg/dl, at months 6, 1.73+/- 0.33 mg/dl; Vs baseline of 1.94+/- 0.37 mg/dl, P<0.05, at respectively). The dosage of cyclosporine, as intended, was significantly reduced from 232 54 mg/dl to 210 51 mg/dl after 6 months observation period (p<0.01). There was no episode of acute rejection after starting MMF with a reduction in cyclosporine.
CONCLUSION
With this clinical trial, we propose that MMF may be effective for prevention of progression of chronic rejection. By addition of MMF, we could reduce the cyclosporine doses without risk of acute rejection and we suggest that it may have an important role for prevention of chronic cyclosporine nephrotoxicity.