Kidney transplantation
Immunosuppression
Conversion to Proliferation Signal Inhibitors–Based Immunosuppressive Regimen in Kidney Transplantation: To Whom and When?

https://doi.org/10.1016/j.transproceed.2011.01.097Get rights and content

Abstract

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.

Section snippets

Methods

Between December 2007 and May 2010, we converted 62 renal transplant recipients from cyclosporine (CsA) or tacrolimus to sirolimus or everolimus for various reasons. None of the patients experienced an acute rejection episode and/or significant proteinuria (500 mg/dL). All patients received SRL (46) or EVR (16) and prednisone with CNI minimization after conversion. (GFRs) Glomerular filtration rates were calculated by the Cockcroft-Gault method of before initiation of PSI (baseline) and at 6

Results

The mean age of the 62 patients including 19 women and 43 mens at transplantation was 38.0 ± 13.1 years. Fifty-four were transplanted from living related and 8 from cadaveric donors. The donor and recipient demographic features are presented in Table 1.

The reasons for conversion were: BK virus nephropathy (n = 4), skin malignancy (n = 1), 1, chronic allograft nephropathy (n = 18), and older donor age (n = 20). Immunosuppressive therapy was converted to a PSI-based triple regimen at 172.0 ±

Discussion

There is no standard therapy to treat deteriorating renal function among transplant recipients. Multiple strategies have been attempted to slow the progression of allograft dysfunction, including addition of mycophenolate mofetil, reduction of CsA dose, and conversion to sirolimus or everolimus (6–8). Attempts to minimize CNI nephrotoxicity by reducing the dose or withdrawing CNI from immunosuppressive regimens have been limited by acute rejection rates.9, 10 In the present study, only 2/62

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