Effect of conversion from azathioprine to mycophenolate mofetil on renal function in stable kidney transplant recipients

Abstract

Abstract

Aim: This study investigated the effect of mycophenolate mofetil (MPA) treatment instead of azathioprine (AZA) on renal function after kidney transplantation. 

Methods: Thirteen of all recipients were taking a cyclosporine-based regimen and serum creatinine levels were above 1.5 mg/dL. In 13 patients, MPA treatment was started instead of AZA. Renal functions were evaluated for 12 months after MPA treatment. 

Results: Serum creatinine levels increased from 2.11±0.48 mg/dL to 2.16±0.72 mg/dL at 12th months. This increase was not statistically significant. Serum creatinine levels decreased in 5 of 13 patients. 

Conclusion: In selected patients, conversion from AZA to MPA may slow down the rate of deterioration in graft functions.

Keywords

• azathioprine,mycophenolate mofetil,kidney transplantation recipient

References

1. Chandraker A, Yeung MY. Overview of care of the adult kidney transplant recipient. UpToDate Aug 2019. Accessed 20 Sep 2019
2. Hart A, Smith JM, Skeans MA, Gustafson SK, Stewart DE, Cherikh WS, Wainright JL, Boyle G, Snyder JJ, Kasiske BL, Israni AK. Kidney. Am J Transplant. 2016 Jan;16 Suppl 2:11-46. doi: 10.1111/ajt.13666.
3. Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant. 2009 Nov;9 Suppl 3:S1-155. doi: 10.1111/j.1600-6143.2009.02834.x.
4. Wagner M, Earley AK, Webster AC, Schmid CH, Balk EM, Uhlig K. Mycophenolic acid versus azathioprine as primary immunosuppression for kidney transplant recipients. Cochrane Database Syst Rev. 2015 Dec 3;(12):CD007746. doi: 10.1002/14651858.CD007746.pub2.
5. Allison AC, Eugui EM. Mycophenolate mofetil and its mechanisms of action. Immunopharmacology. 2000 May;47(2-3):85-118.
6. Bullingham RE1, Nicholls AJ, Kamm BR. Clinical pharmacokinetics of mycophenolate mofetil. Clin Pharmacokinet. 1998 Jun;34(6):429-55.
7. Ekberg H, Mamelok RD, Pearson TC, Vincenti F, Tedesco-Silva H, Daloze P. The challenge of achieving target drug concentrations in clinical trials: experience from the Symphony study. Transplantation. 2009 May 15;87(9):1360-6. doi: 10.1097/TP.0b013e3181a23cb2.
8. Opelz G, Döhler B; Collaborative Transplant Study. Influence of immunosuppressive regimens on graft survival and secondary outcomes after kidney transplantation. Transplantation. 2009 Mar 27;87(6):795-802. doi: 10.1097/TP.0b013e318199c1c7.

9. Khalkhali HR, Ghafari A, Hajizadeh E, Kazemnejad A. Risk factors of long-term graft loss in renal transplant recipients with chronic allograft dysfunction. Exp Clin Transplant. 2010 Dec;8(4):277-82.
10. Birnbaum LM, Lipman M, Paraskevas S, Chaudhury P, Tchervenkov J, Baran D, Herrera-Gayol A, Cantarovich M. Management of chronic allograft nephropathy: a systematic review. Clin J Am Soc Nephrol. 2009;4(4):860.
11. Lang P, Pardon A, Audard V. Long-term benefit of mycophenolate mofetil in renal transplantation. Transplantation. 2005 Feb 15;79(3 Suppl):S47-8.
12. Sollinger HW. Mycophenolate mofetil for the prevention of acute rejection in primary cadaveric renal allograft recipients. U.S. Renal Transplant Mycophenolate Mofetil Study Group. Transplantation. 1995 Aug 15;60(3):225-32.
13. Placebo-controlled study of mycophenolate mofetil combined with cyclosporin and corticosteroids for prevention of acute rejection. European Mycophenolate Mofetil Cooperative Study Group. Lancet. 1995 May 27;345(8961):1321-5.
14. A blinded, randomized clinical trial of mycophenolate mofetil for the prevention of acute rejection in cadaveric renal transplantation. The Tricontinental Mycophenolate Mofetil Renal Transplantation Study Group. Transplantation. 1996 Apr 15;61(7):1029-37.
15. Mycophenolate mofetil in cadaveric renal transplantation. US Renal Transplant Mycophenolate Mofetil Study Group. Am J Kidney Dis. 1999 Aug;34(2):296-303.
16. Remuzzi G, Lesti M, Gotti E, Ganeva M, Dimitrov BD, Ene-Iordache B, Gherardi G, Donati D, Salvadori M, Sandrini S, Valente U, Segoloni G, Mourad G, Federico S, Rigotti P, Sparacino V, Bosmans JL, Perico N, Ruggenenti P. Mycophenolate mofetil versus azathioprine for prevention of acute rejection in renal transplantation (MYSS): a randomised trial. Lancet. 2004 Aug 7-13;364(9433):503-12.
17. Remuzzi G, Cravedi P, Costantini M, Lesti M, Ganeva M, Gherardi G, Ene-Iordache B, Gotti E, Donati D, Salvadori M, Sandrini S, Segoloni G, Federico S, Rigotti P, Sparacino V, Ruggenenti P. Mycophenolate mofetil versus azathioprine for prevention of chronic allograft dysfunction in renal transplantation: the MYSS follow-up randomized, controlled clinical trial. J Am Soc Nephrol. 2007 Jun;18(6):1973-85.
18. Mathew TH. A blinded, long-term, randomized multicenter study of mycophenolate mofetil in cadaveric renal transplantation: results at three years. Tricontinental Mycophenolate Mofetil Renal Transplantation Study Group. Transplantation. 1998 Jun 15;65(11):1450-4.
19. Clayton PA, McDonald SP, Chapman JR, Chadban SJ. Mycophenolate versus azathioprine for kidney transplantation: a 15-year follow-up of a randomized trial. Transplantation. 2012 Jul 27;94(2):152-8. doi: 10.1097/TP.0b013e31825475a3.
20. Nakazawa S, Kishikawa H, Kawamura M, Ueda N, Hirai T, Nishimura K. Conversion to mycophenolate mofetil from azathioprine shows significant positive effect on graft function in long-term past-kidney transplantation stable-state patients. Transplant Proc. 2014;46(2):411-4. doi: 19.1016/j.transproceed.2013.12.038.
21. Ducloux D, Motte G, Billerey C, Bresson-Vautrin C, Vautrin P, Rebibou JM, Saint-Hillier Y, Chalopin JM. Cyclosporin withdrawal with concomitant conversion from azathioprine to mycophenolate mofetil in renal transplant recipients with chronic allograft nephropathy: a 2-year follow-up. Transpl Int. 2002 Sep;15(8):387-92.
22. Meier-Kriesche HU, Steffen BJ, Hochberg AM, Gordon RD, Liebman MN, Morris JA, Kaplan B. Mycophenolate mofetil versus azathioprine therapy is associated with a significant protection against long-term renal allograft function deterioration. Transplantation. 2003 Apr 27;75(8):1341-6.
23. Moore J, Middleton L, Cockwell P, Adu D, Ball S, Little MA, Ready A, Wheatley K, Borrows R. Calcineurin inhibitor sparing with mycophenolate in kidney transplantation: a systematic review and meta-analysis. Transplantation. 2009 Feb 27;87(4):591-605. doi: 10.1097/TP.0b013e318195a421.
24. El-Agroudy AE, El-Dahshan KF, Mahmoud K, Ismail AM, El-Baz M, Shokeir AA, Ghoneim MA. Long-term graft outcome in patients with chronic allograft nephropathy after immunosuppression modifications. Clin Exp Nephrol. 2009 Feb;13(1):66-72. doi: 10.1007/s10157-008-0077-y.
25. Merville P, Bergé F, Deminière C, Morel D, Chong G, Durand D, Rostaing L, Mourad G, Potaux L. Lower incidence of chronic allograft nephropathy at 1 year post-transplantation in patients treated with mycophenolate mofetil. Am J Transplant. 2004 Nov;4(11):1769-75.
26. Gutiérrez Sánchez MJ, Morales Cerdán JM, Belmonte AA. Optimization of immunosuppression by switching from azathioprine to enteric-coated mycophenolate sodium in stable kidney transplant patients. Transplant Proc. 2009 Jul-Aug;41(6):2320-2. doi: 10.1016/j.transproceed.2009.06.154.
27. Dudley C, Pohanka E, Riad H, Dedochova J, Wijngaard P, Sutter C, Silva HT Jr; Mycophenolate Mofetil Creeping Creatinine Study Group. Mycophenolate mofetil substitution for cyclosporine a in renal transplant recipients with chronic progressive allograft dysfunction: the "creeping creatinine" study. Transplantation. 2005 Feb 27;79(4):466-75.
28. Gonzalez Molina M, Seron D, Garcia del Moral R, Carrera M, Sola E, Jesus Alferez M, Gomez Ullate P, Capdevila L, Gentil MA. Mycophenolate mofetil reduces deterioration of renal function in patients with chronic allograft nephropathy. A follow-up study by the Spanish Cooperative Study Group of Chronic Allograft Nephropathy. Transplantation. 2004 Jan 27;77(2):215-20.
29. Garcia R, Pinheiro-Machado PG, Felipe CR, Park SI, Silva LA, Franco MF, Tedesco-Silva H Jr, Medina-Pestana JO. Conversion from azathioprine to mycophenolate mofetil followed by calcineurin inhibitor minimization or elimination in patients with chronic allograft dysfunction. Transplant Proc. 2006 Nov;38(9):2872-8.
30. Ojo AO, Meier-Kriesche HU, Hanson JA, Leichtman AB, Cibrik D, Magee JC, Wolfe RA, Agodoa LY, Kaplan B. Mycophenolate mofetil reduces late renal allograft loss independent of acute rejection. Transplantation. 2000 Jun 15;69(11):2405-9.
31. Stoves J, Newstead CG, Baczkowski AJ, Owens G, Paraoan M, Hammad AQ. A randomized controlled trial of immunosuppression conversion for the treatment of chronic allograft nephropathy. Nephrol Dial Transplant. 2004 Aug;19(8):2113-20.
32. Habas E, Khammaj A, Rayani A. Hematologic side effects of azathioprine and mycophenolate in kidney transplantation. Transplant Proc. 2011 Mar;43(2):504-6. doi: 10.1016/j.transproceed.2011.01.077.