Prospective randomized study of conversion from tacrolimus to cyclosporine A to improve glucose metabolism in patients with posttransplant diabetes mellitus after renal transplantation.
Wissing, Karl M.; Abramowicz, Daniel; WEEKERS, Laurentet al.
[en] Tacrolimus (TAC) increases the risk of posttransplant diabetes (PTDM) compared with cyclosporine A (CYC). The present 12-month, multicenter, investigator-driven, prospective, randomized study was designed to assess whether conversion from tacrolimus to CYC can reverse PTDM after renal transplantation. Predominantly white patients with PTDM according to the 2005 American Diabetes Association criteria were randomized to either replacement of TAC with CYC or continuation of their TAC-based regimen after stratification for type of glucose-lowering therapy, steroid therapy, and hepatitis C status. At 12 months, 14 of 41 patients with complete data in the CYC arm (34%; 95%CI 19%-49%) were free of diabetes, whereas this was the case in only 4 of 39 patients (10%; 95%CI 3%-20%) in the TAC arm (P = .01). At 12 months, 39% of patients in the CYC arm were off glucose-lowering medication vs 13% of patients in the TAC arm (P = .01). The CYC group decreased glycated hemoglobin level during the 12-month follow-up, resulting in significantly lower levels compared with the TAC group (6.0 +/- 0.9% vs 7.1 +/- 1.7% at 12 months; P = .002). In conclusion, replacement of TAC with CYC significantly improves glucose metabolism and has the potential to reverse diabetes during the first year after conversion. (EU Clinical Trials Register No. 2006-001765-42).
Disciplines :
Urology & nephrology
Author, co-author :
Wissing, Karl M.
Abramowicz, Daniel
WEEKERS, Laurent ; Centre Hospitalier Universitaire de Liège - CHU > Service de néphrologie
Budde, Klemens
Rath, Thomas
Witzke, Oliver
Broeders, Nilufer
Kianda, Mireille
Kuypers, Dirk R. J.
Language :
English
Title :
Prospective randomized study of conversion from tacrolimus to cyclosporine A to improve glucose metabolism in patients with posttransplant diabetes mellitus after renal transplantation.
Publication date :
2018
Journal title :
American Journal of Transplantation
ISSN :
1600-6135
eISSN :
1600-6143
Publisher :
Wiley, Hoboken, United States - New Jersey
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
(c) 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.
Hecking M, Werzowa J, Haidinger M, et al. Novel views on new-onset diabetes after transplantation: development, prevention and treatment. Nephrol Dial Transplant. 2013;28(3):550-566.
First MR, Dhadda S, Croy R, Holman J, Fitzsimmons WE. New-onset diabetes after transplantation (NODAT): an evaluation of definitions in clinical trials. Transplantation. 2013;96(1):58-64.
Sharif A, Hecking M, de Vries AP, et al. Proceedings from an international consensus meeting on posttransplantation diabetes mellitus: recommendations and future directions. Am J Transplant. 2014;14(9):1992-2000.
Kasiske BL, Snyder JJ, Gilbertson D, Matas AJ. Diabetes mellitus after kidney transplantation in the United States. Am J Transplant. 2003;3(2):178-185.
Cosio FG, Kudva Y, Van Der Velde M, et al. New onset hyperglycemia and diabetes are associated with increased cardiovascular risk after kidney transplantation. Kidney Int. 2005;67(6):2415-2421
Eide IA, Halden TAS, Hartmann A, Dahle DO, Asberg A, Jenssen T. Associations between posttransplantation diabetes mellitus and renal graft survival. Transplantation. 2017;101(6):1282-1289.
Woodward RS, Schnitzler MA, Baty J, et al. Incidence and cost of new onset diabetes mellitus among U.S. wait-listed and transplanted renal allograft recipients. Am J Transplant. 2003;3(5):590-598.
Rostaing L, Cantarovich D, Mourad G, et al. Corticosteroid-free immunosuppression with tacrolimus, mycophenolate mofetil, and daclizumab induction in renal transplantation. Transplantation. 2005;79(7):807-814.
Kumar MS, Heifets M, Moritz MJ, et al. Safety and efficacy of steroid withdrawal two days after kidney transplantation: analysis of results at three years. Transplantation. 2006;81(6):832-839.
Luan FL, Steffick DE, Ojo AO. New-onset diabetes mellitus in kidney transplant recipients discharged on steroid-free immunosuppression. Transplantation. 2011;91(3):334-341.
Pirsch JD, Henning AK, First MR, et al. New-onset diabetes after transplantation: results from a double-blind early corticosteroid withdrawal trial. Am J Transplant. 2015;15(7):1982-1990.
Knight SR, Morris PJ. Steroid avoidance or withdrawal after renal transplantation increases the risk of acute rejection but decreases cardiovascular risk. A meta-analysis. Transplantation. 2010;89(1):1-14.
Pascual J, Galeano C, Royuela A, Zamora J. A systematic review on steroid withdrawal between 3 and 6 months after kidney transplantation. Transplantation. 2010;90(4):343-349.
Kamar N, Mariat C, Delahousse M, et al. Diabetes mellitus after kidney transplantation: a French multicentre observational study. Nephrol Dial Transplant. 2007;22(7):1986-1993.
Heisel O, Heisel R, Balshaw R, Keown P. New onset diabetes mellitus in patients receiving calcineurin inhibitors: a systematic review and meta-analysis. Am J Transplant. 2004;4(4):583-595.
Roland M, Gatault P, Doute C, et al. Immunosuppressive medications, clinical and metabolic parameters in new-onset diabetes mellitus after kidney transplantation. Transpl Int. 2008;21(6):523-530.
Ghisdal L, Baron C, Le MY, et al. TCF7L2 polymorphism associates with new-onset diabetes after transplantation. J Am Soc Nephrol. 2009;20(11):2459-2467.
Vincenti F, Friman S, Scheuermann E, et al. Results of an international, randomized trial comparing glucose metabolism disorders and outcome with cyclosporine vs tacrolimus. Am J Transplant. 2007;7(6):1506-1514.
Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant. 2009;9(Suppl 3):S1-S155.
Ghisdal L, Bouchta NB, Broeders N, et al. Conversion from tacrolimus to cyclosporine A for new-onset diabetes after transplantation: a single-centre experience in renal transplanted patients and review of the literature. Transpl Int. 2008;21(2):146-151.
Ramos-Cebrian M, Torregrosa JV, Gutierrez-Dalmau A, Oppenheimer F, Campistol JM. Conversion from tacrolimus to cyclosporine could improve control of posttransplant diabetes mellitus after renal transplantation. Transplant Proc. 2007;39(7):2251-2253.
Lorho R, Hardwigsen J, Dumortier J, et al. Regression of new-onset diabetes mellitus after conversion from tacrolimus to cyclosporine in liver transplant patients: results of a pilot study. Clin Res Hepatol Gastroenterol. 2011;35(6–7):482-488.
Oberholzer J, Thielke J, Hatipoglu B, Testa G, Sankary HN, Benedetti E. Immediate conversion from tacrolimus to cyclosporine in the treatment of posttransplantation diabetes mellitus. Transplant Proc. 2005;37(2):999-1000.
Dumortier J, Bernard S, Bouffard Y, Boillot O. Conversion from tacrolimus to cyclosporine in liver transplanted patients with diabetes mellitus. Liver Transpl. 2006;12(4):659-664.
Kaplan B, Schold JD, Meier-Kriesche HU. Long-term graft survival with neoral and tacrolimus: a paired kidney analysis. J Am Soc Nephrol. 2003;14(11):2980-2984.
Bunnapradist S, Daswani A, Takemoto SK. Graft survival following living-donor renal transplantation: a comparison of tacrolimus and cyclosporine microemulsion with mycophenolate mofetil and steroids. Transplantation. 2003;76(1):10-15.
Woodward RS, Kutinova A, Schnitzler MA, Brennan DC. Renal graft survival and calcineurin inhibitor. Transplantation. 2005;80(5):629-633.
Ekberg H, Tedesco-Silva H, Demirbas A, et al. Reduced exposure to calcineurin inhibitors in renal transplantation. N Engl J Med. 2007;357(25):2562-2575.
Silva HT Jr, Yang HC, Meier-Kriesche HU, et al. Long-term follow-up of a phase III clinical trial comparing tacrolimus extended-release/MMF, tacrolimus/MMF, and cyclosporine/MMF in de novo kidney transplant recipients. Transplantation. 2014;97(6):636-641.
American Diabetes Association. Standards of medical care in diabetes. Diabetes Care 2005;28(suppl 1):S4-S36.
Gregoor PJ, de Sevaux RG, Hene RJ, et al. Effect of cyclosporine on mycophenolic acid trough levels in kidney transplant recipients. Transplantation. 1999;68(10):1603-1606.
Wissing KM, Unger P, Ghisdal L, et al. Effect of atorvastatin therapy and conversion to tacrolimus on hypercholesterolemia and endothelial dysfunction after renal transplantation. Transplantation. 2006;82(6):771-778.
McCune TR, Thacker LR II, Peters TG, et al. Effects of tacrolimus on hyperlipidemia after successful renal transplantation: a Southeastern Organ Procurement Foundation multicenter clinical study. Transplantation. 1998;65(1):87-92.
Ligtenberg G, Hene RJ, Blankestijn PJ, Koomans HA. Cardiovascular risk factors in renal transplant patients: cyclosporin A vs tacrolimus. J Am Soc Nephrol. 2001;12(2):368-373.
Artz MA, Boots JM, Ligtenberg G, et al. Improved cardiovascular risk profile and renal function in renal transplant patients after randomized conversion from cyclosporine to tacrolimus. J Am Soc Nephrol. 2003;14(7):1880-1888.
Pascual J, van Hooff JP, Salmela K, Lang P, Rigotti P, Budde K. Three-year observational follow-up of a multicenter, randomized trial on tacrolimus-based therapy with withdrawal of steroids or mycophenolate mofetil after renal transplant. Transplantation. 2006;82(1):55-61.
Gatault P, Kamar N, Buchler M, et al. Reduction of extended-release tacrolimus dose in low-immunological-risk kidney transplant recipients increases risk of rejection and appearance of donor-specific antibodies: a randomized study. Am J Transplant. 2017;17(5):1370-1379.
Webster AC, Woodroffe RC, Taylor RS, Chapman JR, Craig JC. Tacrolimus vs ciclosporin as primary immunosuppression for kidney transplant recipients: meta-analysis and meta-regression of randomised trial data. BMJ. 2005;331(7520):810.
Hecking M, Haidinger M, Doller D, et al. Early basal insulin therapy decreases new-onset diabetes after renal transplantation. J Am Soc Nephrol. 2012;23(4):739-749.
Sharif A, Moore R, Baboolal K. Influence of lifestyle modification in renal transplant recipients with postprandial hyperglycemia. Transplantation. 2008;85(3):353-358.
