Conversion to proliferation signal inhibitors-based immunosuppressive regimen in kidney transplantation: to whom and when?

BACKGROUND: Despite significant advances in kidney transplantation, long-term graft survival has not dramatically improved leading to strategies to change immunosuppression during the posttransplantation period. Proliferation signal inhibitors (PSI) sirolimus or everolimus possess immunosuppressive and antiproliferative properties.

METHODS: We evaluated 62 kidney transplant recipients who underwent conversion from a calcineurin inhibitors (CNI)- to a PSI-based regimen for various reasons. The statistical analysis used SPSS v.15.0 software. We compared calculated glomerular filtration rates (GFRs) before initiation of PSI (baseline) and at 6 months after conversion.

RESULTS: We converted to a PSI-based triple regimen at 172.0 ± 116.5 days after transplantation. The mean serum creatinine at the time of conversion was 2.0 ± 1.1 mg/dL, and it was 1.5 ± 0.7 mg/dL at 6 months after conversion. The rate of change in serum creatinine was -17.1 ± 23.5%. The mean calculated GFR at the time of conversion was 53.6 ± 25.5 mL/min and at 6 months after conversion was 65.8 ± 23.7 mL/min. The rate of change in calculated GFR was 37.9 ± 71.7% (16.4/59.4) at 6 months. Thus we observed significant improvements in creatinine and GFR (P values <.001) after conversion. The Improved GFR significantly correlated with prior dialysis duration and time to conversion (P = .025; P = .012). Patients who had a shorter duration on dialysis and shorter time to conversion experienced more benefit from conversion. Four of the 62 patients reported gastrointestinal toxicity, which resolved with dose reduction in 3 patients: 15 patients experienced acne; 16 reported oral ulcers. None of these toxicities resulted in discontinuation of PSI therapy. Serum cholesterol and tryglyceride levels tended to increase among the conversion group, but they did not show statistical significance.

CONCLUSION: We observed that minimization or withdrawal of CNI with addition of a PSI was a good treatment for deterioration of renal allograft function.