The influence of maintaining immunosuppressive regimen on late results of kidney transplantation

The aim of this study was to compare the efficacy of different calcineurin inhibitors after kidney transplantation. Data of 545 recipients transplanted between years 2007 and 2009 were analyzed. The patients were divided into 2 groups according to received therapy. Patients of the 1^st group (n = 354, males 59%) received cyclosporine, the 2^nd group recipients (n = 191, males 59,5%) were given tacrolimus. Three-year patients and graft survival, the incidence of acute rejection and renal function were compared. The frequency of infections, post-transplant diabetes, arterial hypertension, hyperlipidemia and proteinuria were also studied. Acute rejection episodes were characterized by a decline in kidney function accompanied by well-established diagnostic features on kidney allograft biopsy. Three-year patients survival was 95,3% in group 1 and 89,9% in group 2 (p < 0,12), grafts survival was 94,3 and 91,7% (p < 0,6). Acute rejection episodes within 3 months after transplantation were similar: 15,5% in the 1^st group and 16,2% in the 2^nd group (p < 0,46), after 3 months they were more often in 1^st group: 5,4% vs . 2,4% (p < 0,049). Renal function and proteinuria were similar in compare groups. Mean serum creatinine level was 0,139 ± 0,04 and 0,137 ± 0,01 mM and proteinuria was 0,31 ± 0,032 and 0,33 ± 0,06 g/day in groups 1 and 2, respectively. The rate of infections in the groups were similar: 29,1% vs. 31,8%, respectively (p < 0,32). However the risk of death from infectious was higher in patients who received tacrolimus: 5,8 vs . 1,0, respectively (p < 0,039). Post-transplant diabetes mellitus was more often found in group 2: 31 and 20%, respectively (p < 0,016). Arterial hypertension and hyperlipidemia were found more often in group 1. Our results gave evidence for similar efficacy of cyclosporine and tacrolimus. There are no differences in patient and graft survival, graft function, incidences of acute rejection, infections and proteinuria. There is evidence that arterial hypertension and hyperlipidemia are higher with cyclosporine vs. tacrolimus, there are also evidences that post-transplant diabetes mellitus is more common on tacrolimus than cyclosporine.

трансплантация почки, иммуносупрессия, выживаемость почечных трансплантатов, kidney transplantation, immunosuppression, grafts survival

1. Balzar E., Friman S., Gusmano R., Stolpe J. Randomized trial of tacrolimus versus cyclosporin microemulsion in renal transplantation // Pediatr. Nephrol. 2002. Vol. 17. P. 141–149.

2. Boots J.M., van Duijnhoven E.M., Christiaans M., Nieman F.H., van Suylen R.J., van Hooff J.P. Single-center experience with tacrolimus versus cyclosporine-neoral in renal transplant recipients // Transpl. Int. 2001. Vol. 14. P. 370–383.

3. Bresnahan B.A., Cherikh W.S., Cheng Y. et al. Short-term benefit of tacrolimus versus cyclosporine therapy after renal transplantation: an analysis of UNOS/OPTN database // Am. J. Transplant. 2003 (suppl. 5). P. 462.

4. Bunnapradist S., Dasvani A., Talemoto S. Graft survival following living-donor renal transplantation:a comparison of tacrolimus and cyclosporine microemulsion with mycophenolate mofetil and steroids // Transplantation. 2003. Vol. 76. P. 10–15.

5. Ekberg А., Tedesco-Silva H., Demirbas A. et al. Reduced exposure to calcineurin inhibitors in renal transplantation // N. Engl. J. Med. 2007. Vol. 357. P. 2562.

6. Foster C.E., Philosophe B., Schweitzer E.J. et al. A decade of experience with renal transplantation in African-Americans // Ann. Surg. 2002. Vol. 236. P. 794.

7. Gjertson D.W., Cecka J.M., Terasaki P.I. The relative effects of FK506 and cyclosporine on short- and long-term kidney graft survival // Transplantation. 1995. Vol. 60. P. 1384–1388.

8. Goldfarb-Rumyantzev A.S., Smith L., Shihab F.S., et al. Role of maintenance immunosuppressive regimen in kidney transplant outcome // Clin. J. Am. Soc. Nephrol. 2006. Vol. 1. P. 563.

9. Gonwa T., Johnson C., Ahsan N., Alfrey E.J., Halloran P., Stegall M., Hardy M., Metzger R., Shield C. 3rd, Rocher L., Scandling J., Sorensen J., Mulloy L., Light J., Corwin C., Danovitch G., Wachs M., VanVeldhuisen P., Leonhardt M., Fitzsimmons W.E. Randomized trial of tacrolimus – mycophenolate mofetil or azathioprine versus cyclosporine – mycophenolate mofetil after cadaveric kidney transplantation: Results at three years // Transplantation. 2003. Vol. 75. P. 2048–2053.

10. Halloran P., Mathew T., Tomlanovich S., et al. Mycophenolate mofetil in renal allograft recipients. A pooled efficacy analysis of three randomized, double-blind, clinical studies in prevention of rejection. The International Mycophenolate Mofetil Renal Transplant Study Groups // Transplantation. 1997. Vol. 63. P. 39.

11. Hardinger K.I., Bolul D.I., Schnitzer M.A. et al. A randomized, prospective, pharmacoeconomic trial in renal transplant recipients // Transplantation. 2005. Vol. 80. P. 41.

12. Hariharan S., Johnson C.P., Bresnahan B.A., Taranto S.E., McIntosh M.J., Stablein D. Improved graft survival after renal transplantation in the United States, 1988 to 1996 // N. Engl. J. Med. 2000. Vol. 342. P. 605–612.

13. Heisel O., Heisel R., Balshaw R. et al. New onset diabetes mellitus in patients receiving calcineurin inhibitors: A systematic review and meta-analysis // Am. J. Transplant. 2004. Vol. 4. P. 1.

14. Irish W., Sherrill B., Brennan D.C., Lowell J., Schnitzler M. Three-year post-transplant graft survival in renal-transplant patients with graft function at 6 months receiving tacrolimus or cyclosporine microemulsion within a triple-drug regimen // Transplantatation. 2003. Vol. 76. P. 1686–1690.

15. Jensik S.C. For the FK506 Kidney Transplant Study Group. Tacrolimus (FK506) in kidney transplantation: three-year survival results of the U.S. multicenter, randomized comparative trial // Transplant. Proc. 1998. Vol. 30. P. 1216.

16. Kaplan B., Schold J., Meier-Kriesche H.-U. Long-term graft survival with Neoral and Tacrolimus: A paired kidney analysis // J. Am. Soc. Nephrol. 2003. Vol. 14. P. 2980–2984.

17. Kasiske B.L., Snyder J.J., Gilbertson D., et al. Diabetes mellitus after kidney transplantation in the United States // Am. J. Transplant. 2003. Vol. 3. P. 178.

18. Kramer B.K., Montagnino G., Del Castillo D., Margreiter R., Sperschneider H., Olbricht C.J., Kruger B., Ortuno J., Kohler H., Kunzendorf U., Stummvoll H.K., Tabernero J.M., Muhlbacher F., Rivero M., Arias M. Efficacy and safety of tacrolimus compared with cyclosporin A microemulsion in renal transplantation: 2 year follow-up results // Nephrol. Dial. Transplant. 2005. Vol. 20. P. 968–973.

19. Ligtenberg G., Hene R.J., Blankestijn P.J. et al. Cardiovascular risk factors in renal transplant patients: cyclosporine A versus tacrolimus // J. Am. Soc. Nephrol. 2001. Vol. 12. P. 368.

20. Margreiter R. for the European Tacrolimus versus Cyclosporine Microemulsion Renal Transplant Study Group. Efficacy and safety of tacrolimus compared with cyclosporine microemulsion in renal transplantation: a randomized multicenter study // Lancet. 2002. Vol. 359. P. 741.

21. Mayer A.D. Chronic rejection and graft half-life: five-year follow up of the European tacrolimus multicenter study // Transplant. Proc. 1998. Vol. 34. P. 1491.

22. Murphy G.J., Waller J.R., Sandford R.S., Furness P.N., Nicholson M.L. Randomized clinical trial of the effect of microemulsion cyclosporin and tacrolimus on renal allograft fibrosis // Br. J. Surg. 2003. Vol. 90. P. 680–686.

23. Neylan J.F. for the FK 506 Kidney Transplant Study Group. Racial differences in renal transplantation after immunosupression with tacrolimus versus cyclosporine // Transplantation. 1998. Vol. 65. P. 515.

24. Opelz G. and Döhler B. for the Collaborative Transplant Study. Influence of Immunosuppressive Regimens on Graft Survival and Secondary Outcomes After Kidney Transplantation // Transplantation. 2009. Vol. 87. P. 795–802.

25. Pascual M., Theruvath T., Kawai T., Tolkoff-Rubin N., Cosimi B. Strategies to improve long-term outcomes after renal transplantation // N. Engl. J. Med. 2002. Vol. 346. P. 580–590.

26. Pirsch J.D., Miller J., Deierhoi M.H., Vincenti F., Filo R.S. A comparison of tacrolimus (FK506) and cyclosporine for immunosuppression after cadaveric renal transplantation. FK506 Kidney Transplant Study Group // Transplantation. 1997. Vol. 63. P. 977–983.

27. Shapiro R., Jordan M.L., Scantlebury V., Naraghi R., Hakala T.R., Fung J.J., Starzl T.E. A prospective, randomized trial of tacrolimus/prednisone versus tacrolimus/prednisone/ mycophenolate mofetil in renal transplant recipients // Transplantation. 1999. Vol. 67. P. 411–415.

28. Silva H.T., Yang H.C., Abouljoud M., et al. One-year results with extended-release tacrolimus/MMF, tacrolimus/MMF and cyclosporine/MMF in de novo kidney transplant recipients // Am. J. Transplant. 2007. Vol. 7. P. 595.

29. Sollinger H.W. Mycophenolate mofetil for the prevention of acute rejection in primary cadaveric renal allograft recipients. US Renal Transplant Mycophenolate Mofetil Study Group // Transplantation. 1995. Vol. 60. P. 225–232.

30. Trompeter R., Filler G., Webb N.J. et al. Randomized trial of tacrolimus versus cyclosporine microemulsion in renal transplantation // Pediatr. Nephrol. 2002. Vol. 17. P. 141.

31. Vincenty F. Decade of progress in kidney transplantation.//Transplantation. 2004. Vol. 77. P. 552.

32. Vincenti F., Friman S., Scheuermann E. et al. Results of an international, randomized trial comparing glucose metabolism disorders and outcome with cyclosporine versus tacrolimus // Am. J. Transplant. 2007. Vol. 7. P. 1506.

33. Waid T.H. Prograf as secondary intervention versus continuation of cyclosporine in patients at risk for chronic renal allograft failure (CRAF) results in improved renal function, decreased CV risk, and no increased risk for diabetes // Am. J. Transplant. 2003. Vol. 3 (Suppl 5). P. 436.

34. Webster A.C., Woodroffe R.C., Taylor R.S. et al. Tacrolimus versus cyclosporine as primary immunosuppression for kidney transplant recipients: Meta-analysis and meta-regression of randomised trial data // BMJ. 2005. Vol. 331. P. 810.

35. Woodward R.S., Schnitzler M.A., Baty J. et al. Incidence and cost of new recipients // Am. J. Transplant. 2003. Vol. 3. P. 590.

36. Woodward R.S., Kutinova A., Schnitzler M.A. et al. Renal graft survival and calcineurin inhibitor // Transplantation. 2005. Vol. 80. P. 629.