Skip to main content

Advertisement

SpringerLink
Log in

State-of-the-art immunosuppression protocols for pediatric renal transplant recipients

  • Review
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Immunosuppressive protocols used in pediatric kidney transplantation have changed substantially within the last decade. Many transplant centers now focus on the use of tacrolimus and mycophenolate mofetil in combination with early steroid withdrawal, frequently combined with antibody induction therapy. However, this approach is mainly based on treatment efficacy and—compared to other immunosuppressive regimens used in this context—leads to higher rates of viral infections in patients. In this review I assess data from prospective, interventional trials of immunosuppressive therapy in pediatric kidney transplantation. However, since there is a paucity of randomized controlled trials, I also describe the results of studies with weaker designs. The advantages and disadvantages of different immunosuppressive strategies are discussed. Within this framework I suggest ideas for individualized immunosuppressive regimens based on different stratificators that could effect a change from a ‘one size fits all’ to a tailored approach for initial and maintenance immunosuppressive therapy after renal transplantation in the pediatric setting.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry. www.certain-registry.eu. Accessed 1 July 2017

  2. Hart A, Smith JM, Skeans MA, Gustafson SK, Stewart DE, Cherikh WS, Wainright JL, Kucheryavaya A, Woodbury M, Snyder JJ, Kasiske BL, Israni AK (2017) OPTN/SRTR 2015 annual data report: kidney. Am J Transplant 17[Suppl 1]:21–116

    Article  Google Scholar 

  3. Axelrod DA, Naik AS, Schnitzler MA, Segev DL, Dharnidharka VR, Brennan DC, Bae S, Chen J, Massie A, Lentine KL (2016) National variation in use of immunosuppression for kidney transplantation: a call for evidence-based regimen selection. Am J Transplant 16:2453–2462

    Article  CAS  Google Scholar 

  4. Nehus E, Liu C, Hooper DK, Macaluso M, Kim MO (2015) Clinical practice of steroid avoidance in pediatric kidney transplantation. Am J Transplant 15:2203–2210

    Article  CAS  Google Scholar 

  5. Murad MH, Asi N, Alsawas M, Alahdab F (2016) New evidence pyramid. Evid Based Med 21:125–127

    Article  Google Scholar 

  6. Brooks RJ, Higgins GY, Webster AC (2010) Systematic review of randomized controlled trial quality in pediatric kidney transplantation. Pediatr Nephrol 25:2383–2392

    Article  Google Scholar 

  7. Fine RN, Stablein D, Cohen AH, Tejani A, Kohaut E (2002) Recombinant human growth hormone post-renal transplantation in children: a randomized controlled study of the NAPRTCS. Kidney Int 62:688–696

    Article  CAS  Google Scholar 

  8. Sanchez CP, Kuizon BD, Goodman WG, Gales B, Ettenger RB, Boechat MI, Wang Y, Elashoff R, Salusky IB (2002) Growth hormone and the skeleton in pediatric renal allograft recipients. Pediatr Nephrol 17:322–328

    Article  Google Scholar 

  9. El-Husseini AA, El-Agroudy AE, El-Sayed MF, Sobh MA, Ghoneim MA (2004) Treatment of osteopenia and osteoporosis in renal transplant children and adolescents. Pediatr Transplant 8:357–361

    Article  Google Scholar 

  10. Smith JM, Wong CS, Salamonik EB, Hacker BM, McDonald RA, Mancl LA, Williams BJ, Ibrahim A, Roberts FA (2006) Sonic tooth brushing reduces gingival overgrowth in renal transplant recipients. Pediatr Nephrol 21:1753–1759

    Article  Google Scholar 

  11. Ferraris JR, Pasqualini T, Alonso G, Legal S, Sorroche P, Galich AM, Jasper H, Deflazacort Study Group (2007) Effects of deflazacort vs. methylprednisone: a randomized study in kidney transplant patients. Pediatr Nephrol 22:734–741

    Article  Google Scholar 

  12. Trompeter R, Filler G, Webb NJ, Watson AR, Milford DV, Tyden G, Grenda R, Janda J, Hughes D, Ehrich JH, Klare B, Zacchello G, Bjorn Brekke I, McGraw M, Perner F, Ghio L, Balzar E, Friman S, Gusmano R, Stolpe J (2002) Randomized trial of tacrolimus versus cyclosporin microemulsion in renal transplantation. Pediatr Nephrol 17:141–149

    Article  Google Scholar 

  13. Cransberg K, Cornelissen M, Lilien M, Van Hoeck K, Davin JC, Nauta J (2007) Maintenance immunosuppression with mycophenolate mofetil and corticosteroids in pediatric kidney transplantation: temporary benefit but not without risk. Transplantation 83:1041–1047

    Article  CAS  Google Scholar 

  14. Höcker B, Zencke S, Krupka K, Fichtner A, Pape L, Dello Strologo L, Guzzo I, Topaloglu R, Kranz B, König J, Bald M, Webb NJ, Noyan A, Dursun H, Marks S, Yalcinkaya F, Thiel F, Billing H, Pohl M, Fehrenbach H, Bruckner T, Tönshoff B (2016) Cytomegalovirus infection in pediatric renal transplantation and the impact of chemoprophylaxis with (Val-)Ganciclovir. Transplantation 100:862–870

    Article  Google Scholar 

  15. Benfield MR, Tejani A, Harmon WE, McDonald R, Stablein DM, McIntosh M, Rose S, CCTPT Study Group (2005) A randomized multicenter trial of OKT3 mAbs induction compared with intravenous cyclosporine in pediatric renal transplantation. Pediatr Transplant 9:282–292

    Article  CAS  Google Scholar 

  16. Offner G, Toenshoff B, Hocker B, Krauss M, Bulla M, Cochat P, Fehrenbach H, Fischer W, Foulard M, Hoppe B, Hoyer PF, Jungraithmayr TC, Klaus G, Latta K, Leichter H, Mihatsch MJ, Misselwitz J, Montoya C, Muller-Wiefel DE, Neuhaus TJ, Pape L, Querfeld U, Plank C, Schwarke D, Wygoda S, Zimmerhackl LB (2008) Efficacy and safety of basiliximab in pediatric renal transplant patients receiving cyclosporine, mycophenolate mofetil, and steroids. Transplantation 86:1241–1248

    Article  CAS  Google Scholar 

  17. Fleming JN, Taber DJ, Pilch NA, Srinivas TR, Chavin KD (2016) Yes, we still need IL-2 receptor antagonists. Am J Transplant 16:3308–3309

    Article  CAS  Google Scholar 

  18. Höcker B, Weber LT, Feneberg R, Drube J, John U, Fehrenbach H, Pohl M, Zimmering M, Fründ S, Klaus G, Wuhl E, Tönshoff B (2010) Improved growth and cardiovascular risk after late steroid withdrawal: 2-year results of a prospective, randomised trial in paediatric renal transplantation. Nephrol Dial Transplant 25:617–624

    Article  Google Scholar 

  19. Grenda R, Watson A, Trompeter R, Tonshoff B, Jaray J, Fitzpatrick M, Murer L, Vondrak K, Maxwell H, van Damme-Lombaerts R, Loirat C, Mor E, Cochat P, Milford DV, Brown M, Webb NJ (2010) A randomized trial to assess the impact of early steroid withdrawal on growth in pediatric renal transplantation: the TWIST study. Am J Transplant 10:828–836

    Article  CAS  Google Scholar 

  20. Sarwal MM, Ettenger RB, Dharnidharka V, Benfield M, Mathias R, Portale A, McDonald R, Harmon W, Kershaw D, Vehaskari VM, Kamil E, Baluarte HJ, Warady B, Tang L, Liu J, Li L, Naesens M, Sigdel T, Waskerwitz J, Salvatierra O (2012) Complete steroid avoidance is effective and safe in children with renal transplants: a multicenter randomized trial with three-year follow-up. Am J Transplant 12:2719–2729

    Article  CAS  Google Scholar 

  21. Haller MC, Royuela A, Nagler EV, Pascual J, Webster AC (2016) Steroid avoidance or withdrawal for kidney transplant recipients. Cochrane Database Syst Rev 22:CD005632

    Google Scholar 

  22. Zhang H, Zheng Y, Liu L, Fu Q, Li J, Huang Q, Liu H, Deng R, Wang C (2016) Steroid avoidance or withdrawal regimens in paediatric kidney transplantation: a meta-analysis of randomised controlled trials. PLoS One 11:e0146523

    Article  Google Scholar 

  23. Benfield MR, Bartosh S, Ikle D, Warshaw B, Bridges N, Morrison Y, Harmon W (2010) A randomized double-blind, placebo controlled trial of steroid withdrawal after pediatric renal transplantation. Am J Transplant 10:81–88

    Article  CAS  Google Scholar 

  24. Ettenger R, Tönshoff B, Tedesco H, Dello Strologo L, Marks S, Pape L, Martzloff E, Rauer B, Ng J, Lopez P (2017) Efficacy and safety of everolimus with reduced-exposure tacrolimus and corticosteroid withdrawal in de novo pediatric renal transplant recipients: 12-month results from the CRADLE study In: Abstracts of the 2017 American Transplant Congress. Abstract #569. Am J Transplant 17[Suppl 3]:100

  25. Ahlenstiel-Grunow T, Koch A, Grosshennig A, Fromke C, Sester M, Sester U, Schroder C, Pape L (2014) A multicenter, randomized, open-labeled study to steer immunosuppressive and antiviral therapy by measurement of virus (CMV, ADV, HSV)-specific T cells in addition to determination of trough levels of immunosuppressants in pediatric kidney allograft recipients (IVIST01-trial): study protocol for a randomized controlled trial. Trials 15:324

    Article  Google Scholar 

  26. Staskewitz A, Kirste G, Tonshoff B, Weber LT, Boswald M, Burghard R, Helmchen U, Brandis M, Zimmerhackl LB (2001) Mycophenolate mofetil in pediatric renal transplantation without induction therapy: results after 12 months of treatment. German Pediatric Renal Transplantation study Group. Transplantation 71:638–644

    Article  CAS  Google Scholar 

  27. Henne T, Latta K, Strehlau J, Pape L, Ehrich JH, Offner G (2003) Mycophenolate mofetil-induced reversal of glomerular filtration loss in children with chronic allograft nephropathy. Transplantation 76:1326–1330

    Article  CAS  Google Scholar 

  28. Brunkhorst LC, Fichtner A, Hocker B, Burmeister G, Ahlenstiel-Grunow T, Krupka K, Bald M, Zapf A, Tonshoff B, Pape L (2015) Efficacy and safety of an everolimus- vs. a mycophenolate mofetil-based regimen in pediatric renal transplant recipients. PLoS One 10:e0135439

    Article  Google Scholar 

  29. Smith JM, Martz K, Blydt-Hansen TB (2013) Pediatric kidney transplant practice patterns and outcome benchmarks, 1987-2010: a report of the north American pediatric renal trials and collaborative studies. Pediatr Transplant 17:149–157

    Article  Google Scholar 

  30. Kaabak MM, Babenko NN, Shapiro R, Maschan AA, Zokoev AK, Schekaturov SV, Vyunkova JN, Dymova OV (2017) Eight-year follow-up in pediatric living donor kidney recipients receiving alemtuzumab induction. Pediatr Transplant. https://doi.org/10.1111/petr.12941

  31. Lerch C, Kanzelmeyer NK, Ahlenstiel-Grunow T, Froede K, Kreuzer M, Drube J, Verboom M, Pape L (2017) Belatacept after kidney transplantation in adolescents: a retrospective study. Transpl Int 30:494–501

    Article  CAS  Google Scholar 

  32. Ekberg H, Tedesco-Silva H, Demirbas A, Vitko S, Nashan B, Gurkan A, Margreiter R, Hugo C, Grinyo JM, Frei U, Vanrenterghem Y, Daloze P, Halloran PF, ELITE-Symphony Study (2007) Reduced exposure to calcineurin inhibitors in renal transplantation. N Engl J Med 357:2562–2575

    Article  CAS  Google Scholar 

  33. Vincenti F, Rostaing L, Grinyo J, Rice K, Steinberg S, Gaite L, Moal MC, Mondragon-Ramirez GA, Kothari J, Polinsky MS, Meier-Kriesche HU, Munier S, Larsen CP (2016) Belatacept and long-term outcomes in kidney transplantation. N Engl J Med 374:333–343

    Article  CAS  Google Scholar 

  34. Hertig A, Zuckermann A (2015) Rabbit antithymocyte globulin induction and risk of post-transplant lymphoproliferative disease in adult and pediatric solid organ transplantation: an update. Transpl Immunol 32:179–187

    Article  CAS  Google Scholar 

  35. Stojanovic J, Adamusiak A, Kessaris N, Chandak P, Ahmed Z, Sebire NJ, Walsh G, Jones HE, Marks SD, Mamode N (2017) Immune desensitization allows pediatric blood group incompatible kidney transplantation. Transplantation 101:1242–1246

    Article  CAS  Google Scholar 

  36. Mamode N, Marks S (2016) Desensitization protocols for prospective pediatric renal transplant patients. Pediatr Nephrol 31:1549–1551

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatric Nephrology, Hannover Medical School, Hannover, Germany

    Lars Pape

Authors
  1. Lars Pape
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lars Pape.

Ethics declarations

Conflicts of interest

Lars Pape has received speaker’s honoraria and travel grants from Novartis Pharmaceuticals and travel grants from Astellas and Sanofi Aventis.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pape, L. State-of-the-art immunosuppression protocols for pediatric renal transplant recipients. Pediatr Nephrol 34, 187–194 (2019). https://doi.org/10.1007/s00467-017-3826-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-017-3826-x

Keywords

Search

Navigation