[Immunosuppression and Its Use in Kidney Transplantation]

Overview

Journal Urologe A

Specialty Urology

Date 2015 Oct 14

PMID 26459580

Authors

A Paliege

J Bamoulid

F Bachmann

O Staeck

F Halleck

D Khadzhynov

S Brakemeier

M Durr

K Budde

Affiliations

Soon will be listed here.

Abstract

Background: Current immunosuppressive protocols effectively prevent acute rejection of renal allografts. Extensive drug toxicity and the deleterious effects of long-term immunosuppression are associated with significant morbidity and mortality.

Objectives: The purpose of this article is to provide an overview over modern immunosuppressants and their unwanted side effects and to discuss strategies for improved long-term transplant survival.

Methods: Review of the current topic-related literature and discussion of our own experience.

Results: The use of antibody induction together with an initial combination therapy of calcineurin inhibitors, mycophenolate and steroids is recommended and results in excellent early outcomes. Detrimental effects include an increased incidence of infections, malignomas, and cardiovascular diseases. Long-term transplant survival is impaired by extensive drug toxicity and the frequent development of donor specific antibodies. Reduction of overall cumulative exposure to immunosuppressants or the reduction of specific toxic drugs such as calcineurin inhibitors and steroids may improve long-term results. Alternative immunosuppressants like mTOR inhibitors and belatacept appear to be effective and safe but their long-term effects on patient and allograft survival needs to be established in clinical trials.

Conclusions: Current immunosuppressants provide effective protection from renal allograft rejection. However, their use is complicated by serious side effects. In the future, development of novel immunosuppressants and optimization of minimization strategies may help to improve long-term success after kidney transplantation.

References

Casey M, Meier-Kriesche H . Calcineurin inhibitors in kidney transplantation: friend or foe?. Curr Opin Nephrol Hypertens. 2011; 20(6):610-5. DOI: 10.1097/MNH.0b013e32834b4343. View

van Gelder T, Tedesco Silva H, De Fijter J, Budde K, Kuypers D, Tyden G . Comparing mycophenolate mofetil regimens for de novo renal transplant recipients: the fixed-dose concentration-controlled trial. Transplantation. 2008; 86(8):1043-51. DOI: 10.1097/TP.0b013e318186f98a. View

Bamoulid J, Staeck O, Halleck F, Khadzhynov D, Brakemeier S, Durr M . The need for minimization strategies: current problems of immunosuppression. Transpl Int. 2015; 28(8):891-900. DOI: 10.1111/tri.12553. View

Webster A, Woodroffe R, Taylor R, Chapman J, Craig J . Tacrolimus versus ciclosporin as primary immunosuppression for kidney transplant recipients: meta-analysis and meta-regression of randomised trial data. BMJ. 2005; 331(7520):810. PMC: 1246079. DOI: 10.1136/bmj.38569.471007.AE. View

Maripuri S, Kasiske B . The role of mycophenolate mofetil in kidney transplantation revisited. Transplant Rev (Orlando). 2013; 28(1):26-31. DOI: 10.1016/j.trre.2013.10.005. 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

Hirsch H, Randhawa P . BK polyomavirus in solid organ transplantation. Am J Transplant. 2013; 13 Suppl 4:179-88. DOI: 10.1111/ajt.12110. View

Remuzzi G, Cravedi P, Costantini M, Lesti M, Ganeva M, Gherardi G . 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; 18(6):1973-85. DOI: 10.1681/ASN.2006101153. View

Stahn C, Buttgereit F . Genomic and nongenomic effects of glucocorticoids. Nat Clin Pract Rheumatol. 2008; 4(10):525-33. DOI: 10.1038/ncprheum0898. View

10.

Satyananda V, Shapiro R . Belatacept in kidney transplantation. Curr Opin Organ Transplant. 2014; 19(6):573-7. DOI: 10.1097/MOT.0000000000000134. View

11.

Liefeldt L, Brakemeier S, Glander P, Waiser J, Lachmann N, Schonemann C . Donor-specific HLA antibodies in a cohort comparing everolimus with cyclosporine after kidney transplantation. Am J Transplant. 2012; 12(5):1192-8. DOI: 10.1111/j.1600-6143.2011.03961.x. View

12.

Maes B, Hadaya K, Moor B, Cambier P, Peeters P, De Meester J . Severe diarrhea in renal transplant patients: results of the DIDACT study. Am J Transplant. 2006; 6(6):1466-72. DOI: 10.1111/j.1600-6143.2006.01320.x. View

13.

Murakami N, Riella L, Funakoshi T . Risk of metabolic complications in kidney transplantation after conversion to mTOR inhibitor: a systematic review and meta-analysis. Am J Transplant. 2014; 14(10):2317-27. DOI: 10.1111/ajt.12852. View

14.

Lamb K, Lodhi S, Meier-Kriesche H . Long-term renal allograft survival in the United States: a critical reappraisal. Am J Transplant. 2010; 11(3):450-62. DOI: 10.1111/j.1600-6143.2010.03283.x. View

15.

Bunnapradist S, Lentine K, Burroughs T, Pinsky B, Hardinger K, Brennan D . Mycophenolate mofetil dose reductions and discontinuations after gastrointestinal complications are associated with renal transplant graft failure. Transplantation. 2006; 82(1):102-7. DOI: 10.1097/01.tp.0000225760.09969.1f. View

16.

Ekberg H, Tedesco-Silva H, Demirbas A, Vitko S, Nashan B, Gurkan A . Reduced exposure to calcineurin inhibitors in renal transplantation. N Engl J Med. 2007; 357(25):2562-75. DOI: 10.1056/NEJMoa067411. View

17.

Kaplan B, Qazi Y, Wellen J . Strategies for the management of adverse events associated with mTOR inhibitors. Transplant Rev (Orlando). 2014; 28(3):126-33. DOI: 10.1016/j.trre.2014.03.002. View

18.

Lachmann N, Schonemann C . The differential pathogenicity of HLA antibodies: what a large cross-sectional study can tell us. Clin Transpl. 2014; :377-84. View

19.

Sinclair N . Low-dose steroid therapy in cyclosporine-treated renal transplant recipients with well-functioning grafts. The Canadian Multicentre Transplant Study Group. CMAJ. 1992; 147(5):645-57. PMC: 1336386. View

20.

Curtis J . Corticosteroids and kidney transplantation. Clin J Am Soc Nephrol. 2007; 1(5):907-8. DOI: 10.2215/CJN.02340706. View