CNI MINIMIZATION STRATEGIES

J.O. Medina-pestana¹, V.D. Garcia², E. David-neto³, D.D.B.M. Carvalho⁴, F.L. Contieri⁵, M. Abbud-filho⁶, H. Tedesco silva¹, E. Ikehara^7
1Kidney Transplant, Hospital do Rim e Hipertensao - UNIFESP, Sao Paulo/BRAZIL, ²Nephrology, Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre/BRAZIL, ³Renal Transplantation Service, Hospital das Clinicas - Sao Paulo University School of Medicine, Sao Paulo/BRAZIL, ⁴, Hospital Geral de Bonsucesso, Rio de Janeiro/BRAZIL, ⁵, Hospital Universitário Evangélico de Curitiba, Curitiba/BRAZIL, ⁶Medicina, FAMERP, sao Jose do Rio preto/BRAZIL, ⁷Division Medical, Wyeth Pharmaceuticals, Sao Paulo/BRAZIL

Body: Introduction:Although the tacrolimus-based immunosuppression is highly efficacious in preventing acute rejection early after transplant, its intrinsic nephrotoxocity is critical over the long term. On the other hand, sirolimus is a non-nephrotoxic agent but its de novo use is associated to early complications. Trying to optimize the use of both immunosuppressive agents, Brazilian Investigators proposed the early conversion from tacrolimus to sirolimus at 3 months post transplantation. Methods: Of a total of 300, 237 renal transplant recipients were already enrolled into this 2-year, randomized, prospective, multicenter trial. Initial immunosuppression consisted of tacrolimus 0.1 a 0.2 mg/Kg/day to reach a trough level between 5-15 ng/mL; prednisone and mycophenolate sodium at dose of 720 mg BID. A protocol biopsy was performed at baseline. Patients with proteinuria, GFR< 40 and previous acute rejection > Banff II were not eligible for intervention. The conversion from tacrolimus to sirolimus was done abruptly: patients received a loading dose of 5mg of sirolimus for the first 2 days followed by 3 mg of fixed dose for 1 week, when the first trough level was obtained and the dose adjusted to reach a concentration between 5-15ng/mL thereafter. Results: 117 patients were randomized to be converted to sirolimus at 3 months (61 living, 56 deceased) and 120 randomized to continue on tacrolimus-based regimen (68 living, 52 deceased). 84 (35%) patients received induction therapy, 81 with basiliximab and 3 with thymoglobulin. There was 1 death and 1 graft loss before month 3. Of 149 patients reaching month 3, 30 (20%) patients were not eligible for intervention (13 of sirolimus group and 17 of tacrolimus group). The incidence of acute rejection before month 3 was 16% (38/237). After study intervention 4 episodes of acute rejection were registered, 3 in sirolimus and 1 in tacrolimus group. The mean creatinine was 1.52 + 0.74 mg/dL at month 3 and 1.32 + 0.49 and 1.32 + 0.35 (ns) at month 6, for sirolimus and tacrolimus group, respectively (N= 115). The mean sirolimus concentration of sirolimus at month 6 was 7.9 ng/mL. Conclusion: This initial analysis demonstrates that (1) 20% of patients were not eligible for conversion from tacrolimus to sirolimus; (2) the incidence of acute rejection was more frequent after conversion; (3) no difference in graft function can be observed at 6 months.

Disclosure: All authors have declared no conflicts of interest.