Withdrawal of Cyclosporine or Prednisone Six Months after Kidney Transplantation in Patients on Triple Drug Therapy

Abstract

ABSTRACT. Uncertainty exists regarding the necessity of continuing triple therapy consisting of mycophenolate mofetil (MMF), cyclosporine (CsA), and prednisone (Pred) after kidney transplantation (RTx). At 6 mo after RTx, 212 patients were randomized to stop CsA (n = 63), stop Pred (n = 76), or continue triple drug therapy (n = 73). The MMF dose was 1000 mg twice daily, target CsA trough levels were 150 ng/ml, and Pred dose was 0.10 mg/kg per d. Follow-up was until 24 mo after RTx. Biopsy-proven acute rejection occurred in 14 (22%) of 63 patients after CsA withdrawal compared with 3 (4%) of 76 in the Pred withdrawal group (P = 0.001) and 1 (1.4%) of 73 in the control group (P = 0.0001). Biopsy-proven chronic rejection was present in one patient in the control group, in nine patients after CsA withdrawal (P = 0.006 versus control group); and in four patients after discontinuation of Pred (NS). Graft loss occurred in two versus one patient after CsA or Pred withdrawal, respectively, and in two patients in the control group (NS). Patients who successfully withdrew CsA had a significantly lower serum creatinine during follow-up. Pred withdrawal resulted in a reduction in mean arterial pressure, and the total cholesterol/HDL ratio increased. In conclusion, rapid CsA withdrawal at 6 mo after RTx results in a significantly increased incidence of biopsy-proven acute and chronic rejection. Pred withdrawal was safe and resulted in a reduction in mean arterial pressure. However, patient and graft survival and renal function 2 yr after RTx were not different among groups.

Predictive Factors of Acute Rejection after Early Cyclosporine Withdrawal in Renal Transplant Recipients Who Receive Mycophenolate Mofetil

“…Thus, considering the incidence of AR previously reported in different randomized trials (11)(12)(13) and in our study, the new immunosuppressive drug MMF did not lead to a completely safe CsA discontinuation. Otherwise, the two pivotal trials of CsA elimination conducted with sirolimus showed different results.…”

“…In stable renal transplant recipients, CsA withdrawal under MMF was also found to be a safe procedure on the basis of the risk of AR and renal function (8,9), although histologic deterioration was observed in 50% of patients (10). Finally, the incidence of AR after CsA discontinuation under MMF was evaluated in three randomized trials (11)(12)(13). The risk for AR was found to be significantly increased in two of these studies (11,12), and a trend to a higher incidence was shown in the third one (13).…”

“…Finally, the incidence of AR after CsA discontinuation under MMF was evaluated in three randomized trials (11)(12)(13). The risk for AR was found to be significantly increased in two of these studies (11,12), and a trend to a higher incidence was shown in the third one (13). However, renal function, hypertension, and lipid profile were improved, especially in patients who were withdrawn successfully from CsA.…”

Results of 4-Year Analysis of Conversion from Calcineurin Inhibitors to mTOR Inhibitors in Renal Transplant Patients: Single-Center Experience

“…16,17 We did not observe any increase in acute rejection rates after sirolimus conversion as mentioned in earlier studies. 18 The frequency of acute rejection is not increased in our study. It may be because conversion was made at 30th month.…”

Immunosuppression Minimization

“…The first was reported by Smak Gregoor et al (40) and was designed as a prospective randomized study in primary transplant recipients treated with an immunosuppression regimen consisting of cyclosporine, MMF, and prednisone. The objective of this study was to assess the safety of withdrawal of cyclosporine (50% reduction for 2 wk before discontinuation) or prednisone at 6 mo after transplantation compared with the continuation of triple therapy (Figure 2).…”