SWITCH TO SIROLIMUS-BASED MAINTENANCE IMMUNOSUPPRESSIVE THERAPY IN KIDNEY ALLOGRAFT RECIPIENTS. SINGLE CENTER REPORT:

A69 Aims: Immunosuppression with sirolimus (SRL) may provide an opportunity to avoid exposure to the nephrotoxicity of calcineurin inhibitors (CI). We report a retrospective review in switching kidney transplant recipients from CI to SRL. Methods 27 (M/F: 19/8, age: 40+/-10): 23 patients were primary recipients, whereas 4 (14%) were retransplant recipients with anti-HLA antibodies (range 25-95%). The indications for the switch were biopsy proven CI-nephrotoxicity (n=18) and chronic graft nephropathy (n=2), hemolytic uremic syndrome (n=1), miscellaneous reasons (n=6). The mean time of conversion to SRL was 33.4+/-27 months posttransplantation (2-106). In 17 patients, SRL was introduced (4 mg/d, then the dose was adjusted according trough levels) simultaneously with progressive CI withdrawal: 25% dose reduction/week (slow switch). On the other hand, in 10 patients, CI were stopped at the day of switch and 15 mg of SRL were administered, then 10 mg/d, next the dose was adjusted according trough levels (abrupt switch). All patients were given MMF 0.5g b.i.d., without (n=14) or with (n=13) prednisone (median dose 10mg/d) like prior to switch. SRL trough levels were maintained at 8-12 ng/ml during the 1st posttransplant year and 5-10 ng/ml thereafter. The mean follow-up time was 17.8+/-9.8months (3-35).. Results: Graft function improved in 19 patients (creatinine at conversion 170+/-60 μmol/L) by 15.3% (range 7- 32%) at 3 months post-conversion (p=0.05), the improvement was 18.8% at month 6 (p=0.017). Otherwise, in 4 patients (creatinine at conversion 385+/-130 μmol/L) further progressive graft dysfunction occurred and patients returned to dialysis. In 4 patients SRL was discontinued due to serious adverse events [lymphedema (n=2), interstitial pneumonitis (n=1), severe hepatic toxicity (n=1)]. Other adverse events were increased proteinuria (n=13), aphthous ulcers (n=11), acne (n=11), skin lesions (n=9), anemia (n=9), leukopenia (n=9), thrombocytopenia (n=2), epistaxis (n=7), diarrhea (n=7), increased LDL-cholesterol (n=6). Abrupt switch protocol was associated with early appearance of adverse events (during the 1st month); however, the overall incidence of events was not influenced by switch method. The occurrence of adverse events tended to correlate only with high (median > 10 ng/ml) SRL trough level (R=0.36, p=0.09). Neither acute rejection nor patient mortality occurred. Conclusions: These findings demonstrate that conversion from CI to SRL after kidney transplantation improved graft function if performed in patients without severe graft failure. There was no increased risk of acute rejection even in retransplant patients. Nevertheless, either abrupt or slow protocols were associated with several side effects.