A Comparison of Mycophenolate Mofetil and Calcineurin Inhibitor As Maintenance Immunosuppression for Kidney Transplant Recipients: A Meta-analysis of Randomized Controlled Trials

Overview

Journal Turk J Med Sci

Specialty General Medicine

Date 2020 Dec 28

PMID 33356028

Authors

Jin Deng

Yi Lu

Lihong He

Jihong Ou

Hongping Xie

Affiliations

Soon will be listed here.

Abstract

Background/aim: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the comparison and its timing between mycophenolate mofetil (MMF) and calcineurin inhibitor (CNI) as maintenance immunosuppression for kidney transplant recipients.

Materials And Methods: The RCTs of MMF versus CNI as maintenance immunosuppression for kidney transplant recipients were searched from PubMed, Embase, Cochrane Central Register of Controlled Trials (CCRCT), and ClinicalTrials.gov. After screening relevant RCTs, two authors independently assessed the quality of included studies and performed a meta-analysis using RevMan5.3. Relative risk (RR) was used to report dichotomous data, while mean difference (MD) with 95% confidence interval (CI) was used to report continuous outcomes. The analysis was conducted using the random-effect model due to the expected heterogeneity among different studies. Four subgroups were allocated to compare MMF with CNI as maintenance immunosuppression: (1) after 3 months of CNI-based therapy, (2) after 6 months of CNI-based therapy, (3) after 12 months of CNI-based therapy, and (4) in recipients with allograft dysfunction.

Results: Twelve RCTs with 950 renal transplant recipients were included. This meta-analysis presented the following results upon comparison between MMF and CNI as maintenance immunosuppression for kidney transplant recipients: (1) MMF significantly improved the glomerular filtration rate (GFR) not only in the comparison performed after 3, 6, or 12 months of CNI-based therapy but also in the comparison of recipients with allograft dysfunction, (2) MMF may increase the risk of acute rejection in the comparison performed after 3 months of CNI-based therapy, but no increase was noted in the comparison performed after 6 or 12 months of CNI- based therapy.

Conclusion: Our present meta-analysis suggested that MMF followed at least 6 months of CNI-based therapy is an effective maintenance immunosuppressive regimen for kidney transplant recipients to improve renal function but not increase rejection.

References

Higgins J, Thompson S . Quantifying heterogeneity in a meta-analysis. Stat Med. 2002; 21(11):1539-58. DOI: 10.1002/sim.1186. View

Stevens R, Foster K, Miles C, Kalil A, Florescu D, Sandoz J . A Randomized 2x2 Factorial Clinical Trial of Renal Transplantation: Steroid-Free Maintenance Immunosuppression with Calcineurin Inhibitor Withdrawal after Six Months Associates with Improved Renal Function and Reduced Chronic Histopathology. PLoS One. 2015; 10(10):e0139247. PMC: 4605789. DOI: 10.1371/journal.pone.0139247. View

Hazzan M, Labalette M, Copin M, Glowacki F, Provot F, Pruv F . Predictive factors of acute rejection after early cyclosporine withdrawal in renal transplant recipients who receive mycophenolate mofetil: results from a prospective, randomized trial. J Am Soc Nephrol. 2005; 16(8):2509-16. DOI: 10.1681/ASN.2005030312. View

Moore J, Middleton L, Cockwell P, Adu D, Ball S, Little M . Calcineurin inhibitor sparing with mycophenolate in kidney transplantation: a systematic review and meta-analysis. Transplantation. 2009; 87(4):591-605. DOI: 10.1097/TP.0b013e318195a421. View

Yildirim A . The importance of patient satisfaction and health-related quality of life after renal transplantation. Transplant Proc. 2006; 38(9):2831-4. DOI: 10.1016/j.transproceed.2006.08.162. View

Ciancio G, Miller J, Gonwa T . Review of major clinical trials with mycophenolate mofetil in renal transplantation. Transplantation. 2005; 80(2 Suppl):S191-200. DOI: 10.1097/01.tp.0000187035.22298.ba. View

Shipkova M, Armstrong V, Oellerich M, Wieland E . Mycophenolate mofetil in organ transplantation: focus on metabolism, safety and tolerability. Expert Opin Drug Metab Toxicol. 2006; 1(3):505-26. DOI: 10.1517/17425255.1.3.505. View

Albano L, Alamartine E, Toupance O, Moulin B, Merville P, Rerolle J . Conversion from everolimus with low-exposure cyclosporine to everolimus with mycophenolate sodium maintenance therapy in kidney transplant recipients: a randomized, open-label multicenter study. Ann Transplant. 2012; 17(1):58-67. DOI: 10.12659/aot.882637. View

de Wit G, Ramsteijn P, de Charro F . Economic evaluation of end stage renal disease treatment. Health Policy. 1998; 44(3):215-32. DOI: 10.1016/s0168-8510(98)00017-7. View

10.

Anand S, Bitton A, Gaziano T . The gap between estimated incidence of end-stage renal disease and use of therapy. PLoS One. 2013; 8(8):e72860. PMC: 3758352. DOI: 10.1371/journal.pone.0072860. View

11.

Molina M, Seron D, Garcia Del Moral R, Carrera M, Sola E, Jesus Alferez M . 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; 77(2):215-20. DOI: 10.1097/01.TP.0000100684.59784.FF. View

12.

Cransberg K, Cornelissen M, Lilien M, van Hoeck K, Davin J, Nauta J . Maintenance immunosuppression with mycophenolate mofetil and corticosteroids in pediatric kidney transplantation: temporary benefit but not without risk. Transplantation. 2007; 83(8):1041-7. DOI: 10.1097/01.tp.0000260146.57898.9c. View

13.

Bongiovanni I, Couillerot-Peyrondet A, Sambuc C, Dantony E, Elsensohn M, Sainsaulieu Y . [Cost-effectiveness analysis of various strategies of end-stage renal disease patients' care in France]. Nephrol Ther. 2016; 12(2):104-15. DOI: 10.1016/j.nephro.2015.10.004. View

14.

Schrama Y, Joles J, van Tol A, Boer P, Koomans H, Hene R . Conversion to mycophenolate mofetil in conjunction with stepwise withdrawal of cyclosporine in stable renal transplant recipients. Transplantation. 2000; 69(3):376-83. DOI: 10.1097/00007890-200002150-00012. View

15.

Pascual M, Theruvath T, Kawai T, Tolkoff-Rubin N, Cosimi A . Strategies to improve long-term outcomes after renal transplantation. N Engl J Med. 2002; 346(8):580-90. DOI: 10.1056/NEJMra011295. View

16.

Stoves J, Newstead C, Baczkowski A, Owens G, Paraoan M, Hammad A . A randomized controlled trial of immunosuppression conversion for the treatment of chronic allograft nephropathy. Nephrol Dial Transplant. 2004; 19(8):2113-20. DOI: 10.1093/ndt/gfh188. View

17.

Merville P, Berge F, Deminiere C, Morel D, Chong G, Durand D . Lower incidence of chronic allograft nephropathy at 1 year post-transplantation in patients treated with mycophenolate mofetil. Am J Transplant. 2004; 4(11):1769-75. DOI: 10.1111/j.1600-6143.2004.00533.x. View

18.

McGrath J, Shehata M . Chronic allograft nephropathy: prospective randomised trial of cyclosporin withdrawal and mycophenolate mofetil or tacrolimus substitution. Transplant Proc. 2001; 33(3):2193-5. DOI: 10.1016/s0041-1345(01)01939-x. View

19.

Goldfarb D . The natural history of chronic allograft nephropathy. J Urol. 2005; 173(6):2106. View

20.

Schnuelle P, van der Heide J, Tegzess A, Verburgh C, Paul L, Johannes van der Woude F . Open randomized trial comparing early withdrawal of either cyclosporine or mycophenolate mofetil in stable renal transplant recipients initially treated with a triple drug regimen. J Am Soc Nephrol. 2002; 13(2):536-543. DOI: 10.1681/ASN.V132536. View