Safe conversion of mycophenolate mofetil to azathioprine in kidney transplant recipients with sirolimus-based immunosuppression.

AIM: Mycophenolate mofetil (MMF) is a powerful immunosuppressive drug with established efficacy and safety. The long-term use of MMF may bring increased risk of for infection and malignancy and also increased cost of transplantation. The search for minimization of immunosuppressive protocol has led to an open randomized clinical trial of conversion from MMF to azathioprine (AZA). METHODS: A total of 50 kidney allograft recipients treated with prednisone, sirolimus and MMF were randomized into two groups: converted (AZA group) and continuing (MMF group). The average duration of MMF therapy prior to conversion was 43 months in each group. Inclusion criteria included: patients with serum creatinine levels of less than 200 micromol/L; no past history of acute vascular rejection or recent acute rejection 6 months before randomization; and normal liver function tests. RESULTS: Baseline demographics were similar in the two groups. During the 12 month observation period, there were no acute rejection episodes in either group. There were no significant differences in overall patient or graft survival or function. AZA-treated patients had a lower incidence of gastrointestinal complications (P=0.03). Daily cost reduction in the AZA group was more than $US8.79/day per patient. CONCLUSION: In general, replacing MMF with AZA in stable renal transplant recipients is well tolerated and was cost effective with no increased risk of rejection. As the this study was on relatively small samples, larger and longer follow-up studies will be needed to confirm these expected advantages for the long-term outcome and to assess the long-term safety of this minimization of immunosuppressive therapy.

Long-term graft outcome in patients with chronic allograft nephropathy after immunosuppression modifications.

BACKGROUND/AIM: This retrospective study was conducted to assess the efficacy and safety of immunosuppression conversion on progression of chronic allograft nephropathy (CAN). METHODS: One-hundred and seventy-four cyclosporin (CsA)-treated renal transplant recipients were studied. Patients were included if they had a biopsy-proven CAN (mild to moderate) with serum creatinine < or =3.5 mg/dL. Patient treatment was switched to either: (A) MMF/reduced dose CsA (MMF for azathioprine (Aza); n = 132); or (B) Aza/Tac for CsA (n = 42). Patient records were checked for graft function and survival, and for co-morbidities after conversion. RESULTS: Mean follow-up before conversion was 52.2 +/- 31.1 and 47.9 +/- 27.4 months for groups A and B, respectively. There was significant deterioration of graft function in group B after five years (P < 0.5). Ten-year actuarial graft survival was 38% in group A and 19% in group B (P = 0.04). Nine patients (five patients and four patients in groups A and B, respectively) started dialysis within 12 months. Tacrolimus-treated patients had a lower insignificant incidence of hyperlipidemia (P = 0.05), but a significantly higher incidence of diabetes mellitus (P = 0.04).There was no significant change or difference in blood pressure between groups. CONCLUSIONS: Our results suggest that in patients with CAN and deteriorating allograft function, CsA minimization and addition of MMF achieved favorable efficacies in retarding the decline of graft function. Further prospective studies with larger cohorts are needed for validation.