A Four-drug Combination Therapy Consisting of Low-dose Tacrolimus, Low-dose Mycophenolate Mofetil, Corticosteroids, and Mizoribine in Living Donor Renal Transplantation: A Randomized Study

Overview

Journal SAGE Open Med

Publisher Sage Publications

Specialty General Medicine

Date 2016 May 28

PMID 27231549

Citations 2

Authors

Tian-Zhong Yan

Xiao-Qiang Wu

Lu Rong

Affiliations

Soon will be listed here.

Abstract

Objective: We compared a three-drug combination therapy (control group) consisting of tacrolimus, mycophenolate mofetil, and corticosteroids in living donor renal transplantation with a four-drug combination therapy (study group), in which the doses of tacrolimus and mycophenolate mofetil were halved and the immunosuppressive drug mizoribine was added, in order to determine whether the incidence rates of acute rejection after transplantation between the study group and the control group are similar, whether the study group regimen prevents the occurrence of calcineurin inhibitor-induced renal damage, and whether the study group regimen prevents adverse effects such as diarrhea caused by mycophenolate mofetil.

Methods: We investigated the incidence of acute rejection, serum creatinine levels, and estimated glomerular filtration rate and the incidence of adverse effects such as diarrhea.

Results: There was no significant difference between the two groups in the incidence of acute rejection. Renal function (estimated glomerular filtration rate and serum creatinine) was maintained in the control group whereas in the study group renal function gradually improved, with a statistical difference observed at 12 months. The incidence of gastrointestinal symptoms including diarrhea was significantly higher in the control group than in the study group. There was no significant difference in the incidence of cytomegalovirus infection and other adverse effects.

Conclusion: These results suggest the study group therapy is an effective regimen in preventing acute rejection and the deterioration of renal function. These results also show this therapy can reduce the incidence of adverse effects such as gastrointestinal symptoms.

Citing Articles

Efficacy and Safety of Tacrolimus-Based Maintenance Regimens in De Novo Kidney Transplant Recipients: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

T A M, Chng R, Yau W Ann Transplant. 2021; 26:e933588.

PMID: 34963678 PMC: 8721964. DOI: 10.12659/AOT.933588.

The effectiveness of new triple combination therapy using synthetic disease-modifying anti-rheumatic drugs with different pharmacological function against rheumatoid arthritis: the verification by an in vitro and clinical study.

Hirai T, Ikeda K, Fujishiro M, Tsushima H, Hayakawa K, Suzuki S Clin Rheumatol. 2016; 36(1):51-58.

PMID: 27783236 DOI: 10.1007/s10067-016-3458-8.

References

BEHREND M . Adverse gastrointestinal effects of mycophenolate mofetil: aetiology, incidence and management. Drug Saf. 2001; 24(9):645-63. DOI: 10.2165/00002018-200124090-00002. View

Nankivell B, Borrows R, Fung C, OConnell P, Allen R, Chapman J . The natural history of chronic allograft nephropathy. N Engl J Med. 2003; 349(24):2326-33. DOI: 10.1056/NEJMoa020009. View

Ishikawa H . Mizoribine and mycophenolate mofetil. Curr Med Chem. 1999; 6(7):575-97. View

Kawasaki Y . Mizoribine: a new approach in the treatment of renal disease. Clin Dev Immunol. 2010; 2009:681482. PMC: 2801010. DOI: 10.1155/2009/681482. View

MATHEW T . 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; 65(11):1450-4. DOI: 10.1097/00007890-199806150-00007. View

Darji P, Vijayaraghavan R, Thiagarajan C, Sharma R, Subbarao B, Pishardy R . Conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in renal transplant recipients with gastrointestinal tract disorders. Transplant Proc. 2008; 40(7):2262-7. DOI: 10.1016/j.transproceed.2008.07.041. View

Yoshimura N, Ushigome H, Matsuyama M, Nobori S, Suzuki T, Sakai K . The efficacy and safety of high-dose mizoribine in ABO-incompatible kidney transplantation using anti-CD20 and anti-CD25 antibody without splenectomy treatment. Transplant Proc. 2012; 44(1):140-3. DOI: 10.1016/j.transproceed.2011.12.009. View

Shihab F, Bennett W, Tanner A, Andoh T . Mechanism of fibrosis in experimental tacrolimus nephrotoxicity. Transplantation. 1998; 64(12):1829-37. DOI: 10.1097/00007890-199712270-00034. View

Humar A, Lebranchu Y, Vincenti F, Blumberg E, Punch J, Limaye A . The efficacy and safety of 200 days valganciclovir cytomegalovirus prophylaxis in high-risk kidney transplant recipients. Am J Transplant. 2010; 10(5):1228-37. DOI: 10.1111/j.1600-6143.2010.03074.x. View

10.

Mihatsch M, Kyo M, Morozumi K, Yamaguchi Y, Nickeleit V, Ryffel B . The side-effects of ciclosporine-A and tacrolimus. Clin Nephrol. 1998; 49(6):356-63. View

11.

Lo A . Strategies to prevent chronic allograft nephropathy in kidney transplantation: focus on calcineurin inhibitors. Prog Transplant. 2004; 14(2):157-64. DOI: 10.1177/152692480401400210. View

12.

Kusumi T, Tsuda M, Katsunuma T, Yamamura M . Dual inhibitory effect of bredinin. Cell Biochem Funct. 1989; 7(3):201-4. DOI: 10.1002/cbf.290070308. View

13.

Bulatova N, Yousef A, Al-Khayyat G, Qosa H . Adverse effects of tacrolimus in renal transplant patients from living donors. Curr Drug Saf. 2011; 6(1):3-11. DOI: 10.2174/157488611794480043. View

14.

Shiraki K, Ishibashi M, Okuno T, Kokado Y, Takahara S, Yamanishi K . Effects of cyclosporine, azathioprine, mizoribine, and prednisolone on replication of human cytomegalovirus. Transplant Proc. 1990; 22(4):1682-5. View

15.

Yoshimura N, Ushigome H, Akioka K, Nobori S, Suzuki T, Sakai K . The beneficial effect of high-dose mizoribine combined with cyclosporine, basiliximab, and corticosteroids on CMV infection in renal transplant recipients. Clin Exp Nephrol. 2012; 17(1):127-33. DOI: 10.1007/s10157-012-0669-4. View

16.

Koyama H, Tsuji M . Genetic and biochemical studies on the activation and cytotoxic mechanism of bredinin, a potent inhibitor of purine biosynthesis in mammalian cells. Biochem Pharmacol. 1983; 32(23):3547-53. DOI: 10.1016/0006-2952(83)90301-5. View

17.

Randhawa P, Shapiro R, Jordan M, Starzl T, Demetris A . The histopathological changes associated with allograft rejection and drug toxicity in renal transplant recipients maintained on FK506. Clinical significance and comparison with cyclosporine. Am J Surg Pathol. 1993; 17(1):60-8. PMC: 3229279. DOI: 10.1097/00000478-199301000-00007. View

18.

Takahara S, Takahashi K, Akiyama T, Uchida K, Tanabe K, Amada N . Randomized comparative trial of mizoribine versus mycophenolate mofetil in combination with tacrolimus for living donor renal transplantation. Clin Exp Nephrol. 2013; 17(6):899-904. DOI: 10.1007/s10157-013-0780-1. View

19.

Solez K, Vincenti F, Filo R . Histopathologic findings from 2-year protocol biopsies from a U.S. multicenter kidney transplant trial comparing tarolimus versus cyclosporine: a report of the FK506 Kidney Transplant Study Group. Transplantation. 1999; 66(12):1736-40. DOI: 10.1097/00007890-199812270-00029. View

20.

Xing S, Yang J, Zhang X, Zhou P . Comparative efficacy and safety of mizoribine with mycophenolate mofetil for Asian renal transplantation--a meta-analysis. Clin Biochem. 2014; 47(7-8):663-9. DOI: 10.1016/j.clinbiochem.2014.01.014. View