CLINICAL IMMUNOSUPPRESSION - KIDNEY LATE

F. Tinti¹, A. Meçule¹, L. Poli², A. Bachetoni², I. Nofroni³, I. Umbro¹, M. Barile¹, P. Berloco², A.P. Mitterhofer^1
1Nephrology, Sapienza University of Rome, Rome/ITALY, ²Surgery And Transplant Organs, Sapienza University of Rome, Rome/ITALY, ³, Sapienza University of Rome, Rome/ITALY

Body: Introduction Advagraf® is an extended release formulation of tacrolimus that should be administered once daily. Tacrolimus can be safely converted from standard twice daily formulation (Prograf®) to the same dose (1mg:1mg) of once daily dosing tacrolimus (m-Tac) maintaining an equivalence of exposure at steady state with a high similar correlation between area under the curve, trough levels minimal concentration (Cmin) and a substantially reduced peak level. Chronic rejection or chronic allograft nephropathy is the most common cause of graft failure. Calcineurin inhibitors toxicity is principally involved and non-compliance is an important problem in chronic rejection. Moreover adverse effects such as posttransplant diabetes mellitus, dyslipidemia, hypertension, and toxicity of tacrolimus play an important role in posttransplant cardiovascular risk factors (CV-RF). It has been demonstrated that avoiding tacrolimus peak level and its diabetogenic effect lead to a better control on glycemic metabolism. The aim of our study was to observe the effects of conversion to the m-Tac therapy on graft function and CV-RF in stable transplant kidney recipients. Methods From January 2009 to February 2010 we selected 2 groups of 23 (Group 1) and 20 (Group 2) patients respectively, with a stable kidney transplant, treated with Prograf for more than 6 months and receiving a triple immunosuppression regimen (tacrolimus, micophenolic acid and steroids). Group 1, was converted to once daily tacrolimus at the same dose (1mg: 1 mg) and Group 2 was maintained on twice daily regimen. In Group 1, tacrolimus trough levels, serum creatinine, urea, GFR evaluated with MDRD, glycemia, total-, HDL- and LDL-cholesterol, and blood pressure were performed monthly since 6 months before conversion, on day 0 (time of conversion), on day 15 and monthly for 6 months after conversion In Group 2, the same parameters were evaluated at the same time. Both groups were their own control arm and Group 1 was compared with Group 2 after conversion. Mean variations and total area of distributions were evaluated with a T-Student test for paired data. Results In Group 1 we observed a significant reduction of tacrolimus Cmin (p=0.005) maintaining therapeutic levels, serum creatinine (p=0.000), glucose blood levels (p=0.022) and a significant increasing of GFR (p=0.014), after conversion, whereas Group 2 did not show any modification of considered parameters. Tacrolimus Cmin, serum creatinine, glycemia and triglycerides showed a significant reduction between the two groups after conversion (p=0.002, 0.019, 0.002 and 0.001 respectively). Blood pressure values remained stable inside and between the two groups after conversion, as well as urea, total-, HDL- and LDL-cholesterole. Conclusion In our study the conversion from twice daily formulation to m-Tac results in a significant improvement of renal function parameters and CV-RF. In our opinion the m-Tac therapy in stable kidney transplant patients may be associated with better long-term graft and patient survival.

Disclosure: All authors have declared no conflicts of interest.