Influence of sirolimus on proteinuria in de novo kidney transplantation with expanded criteria donors: comparison of two CNI-free protocols

Background. The contribution of mammalian target of rapamycin (mTOR) inhibitors to proteinuria is controversial. The aim was to analyse proteinuria in suboptimal kidney calcineurin inhibitor-(CNI) free de novo immunosuppression. Methods. All patients from our centre with donors >60 years and CNI-free treatment were included (n ¼ 108). Patients were divided into two groups: (i) SRL group: sirolimus (SRL) þ prednisone þ mycophenolate mofetil (MMF) þ antiCD25; (ii) MMF group: prednisone þ MMF w/ or w/o antiCD25 (n ¼ 75). Follow-up was 12 months. Results. Donors were slightly younger in the SRL group (68 vs 71 years; P < 0.05), receptor age (67 vs 65 years) was not significantly different. Patient survival in the MMF group was 88 vs 94% in the SRL group, however, these differences did not reach statistical significance. One-year graft survival censored for death was 83% in the MMF group and 94% in the SRL group. Acute rejection rate was 45% in the MMF and 15% in the SRL group (P < 0.01). The incidence of CNI introduction was higher in the MMF-group (35 vs 5; P < 0.05). The intention-to-treat analysis revealed significant differences of proteinuria [SRL vs MMF at 12 months: 461 (163–6988) vs 270 (53–3029) mg/day], which did not exist in the on-therapy (OT) analysis [SRL vs MMF at 12 months: 357 (199–1428) vs 279 (53–3029) mg/day]. New onset nephrotic range proteinuria seemed to occur slightly more frequently in SRL patients (3/33 vs 1/75; P ¼ 0.049), however, all four cases occurred in a context of recurrent disease, or previous drug-independent damage or non-adherence. All of these patients were converted to CNI. Conclusion. SRL-based compared with MMF-based treatment in kidney transplantation with advanced age donors is associated with an acceptable outcome, however, with increased proteinuria in the intentionto-treat analysis. A large subgroup of the patients in the MMF group experienced acute rejection and required conversion to CNI.