Pediatric Nephrology

, Volume 28, Issue 8, pp 1293–1298 | Cite as

Long-term side effects of treatment with mTOR inhibitors in children after renal transplantation

  • Birgitta Kranz
  • Anne-Margret Wingen
  • Udo Vester
  • Jens König
  • Peter F. Hoyer
Original Article

Abstract

Background

mTOR inhibitors (mTORI) have emerged as alternative and additive immunosuppressive agents in pediatric renal transplantation (pRTx). Their immunosuppressive, anti-proliferative, and anti-neoplastic mechanisms have been described to be effective, whereas some side effects are alarming. In particular, growth and pubertal development are of concern. The aim of this study was to look for long-term side effects of mTORI therapy in pRTx.

Patients and methods

The retrospective analysis focused on side effects, growth, and pubertal development under mTORI therapy in 31 children. Eighteen children were routinely monitored for estradiol, testosterone, LH, and FSH levels.

Results

The occurrence of bacterial infections, lymphoceles, myelosuppression, and the course of overall linear growth was comparable with other pediatric renal transplant cohorts. According to the clinical puberty status, all but one patient showed normal age-related development in parallel to normal serum hormone levels. Only one patient experienced cytomegaly virus infection under mTORI, no post-transplant lymphoproliferative disorders (PTLD) occurred.

Conclusions

Long-term mTORI therapy is safe in pRTx. No negative impact on growth and pubertal development was observed.

Keywords

Pediatric renal transplantation Growth Pubertal development Acute rejection Everolimus Sirolimus 

References

  1. 1.
    North American Pediatric Renal Trial and Collaborative Studies (NAPRTCS) (2010) annual transplant report https://web.emmes.com/study/ped/annlrept/2010_Report.pdf
  2. 2.
    Gaumann A, Schlitt HJ, Geissler EK (2008) Immunosuppression and tumor development in organ transplant recipients: the emerging dualistic role of rapamycin. Transpl Int 21:207–217CrossRefPubMedGoogle Scholar
  3. 3.
    Ettenger R, Hoyer PF, Grimm P, Webb N, Loirat C, Mahan JD, Mentser M, Niaudet P, Offner G, Vandamme-Lombaerts R, Hexham JM, Everolimus Pediatric Study Group (2008) Multicenter trial of everolimus in pediatric renal transplant recipients: results at three years. Pediatr Transplant 12:456–463CrossRefPubMedGoogle Scholar
  4. 4.
    Pape L, Lehner F, Blume C, Ahlenstiel T (2011) Pediatric kidney transplantation followed by de novo therapy with everolimus, low-dose cyclosporine A, and steroid elimination: 3-year data. Transplantation 92:658–662CrossRefPubMedGoogle Scholar
  5. 5.
    Powell HR, Kara T, Jones CL (2007) Early experience with conversion to sirolimus in a pediatric renal transplant population. Pediatr Nephrol 22:1773–1777CrossRefPubMedGoogle Scholar
  6. 6.
    Kasap B (2011) Sirolimus in pediatric renal transplantation. Pediatr Transpl 15:673–685CrossRefGoogle Scholar
  7. 7.
    Schwartz GJ, Haycock GB, Edelmann CM, Spitzer A (1976) A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 58:259–263PubMedGoogle Scholar
  8. 8.
    Schwartz GJ, Gauthier B (1985) A simple estimate of glomerular filtration rate in boys. J Pediatr 106:522–526CrossRefPubMedGoogle Scholar
  9. 9.
    Vester U, Kranz B, Nadalin S, Paul A, Becker J, Hoyer PF (2005) Sirolimus rescue of renal failure in children after combined liver-kidney transplantation. Pediatr Nephrol 20:686–689CrossRefPubMedGoogle Scholar
  10. 10.
    Hymes LC, Warshaw BL (2011) Five-year experience using sirolimus-based calcineurine inhibitor-free immunosuppression in pediatric renal transplantation. Pediatr Transplant 15:437–441CrossRefPubMedGoogle Scholar
  11. 11.
    Alvarez-Garcia O, Carbajo-Pérez E, Garcia E, Gil H, Molinos I, Rodriguez J, Ordoñez FA, Santos F (2007) Rapamycin retards growth and causes marked alterations in the growth plate of young rats. Pediatr Nephrol 22:954–961CrossRefPubMedGoogle Scholar
  12. 12.
    Aoki MS, Miyabara EH, Soares AG, Saito ET, Moriscot AS (2006) mTOR pathway inhibition attenuates skeletal muscle growth induced by stretching. Cell Tissue Res 324:149–156CrossRefPubMedGoogle Scholar
  13. 13.
    Guba M, Pratschke J, Hugo C, Krämer BK, Nohr-Westphal C, Brockmann J, Andrassy J, Reinke P, Pressmar K, Hakenberg O, Fischereder M, Pascher A, Illner WD, Banas B, Jauch KW, SMART-Study Group (2010) Renal function, efficacy and safety of sirolimus and mycophenolate mofetil after short-term calcineurin inhibitor-based quadruple therapy in de novo renal transplant recipients: one-year analysis of a randomized multicenter trial. Transplantation 90:175–183CrossRefPubMedGoogle Scholar
  14. 14.
    Hymes LC, Warshaw BL (2011) Linear growth in pediatric renal transplant recipients receiving sirolimus. Pediatr Transplant 15:570–572PubMedGoogle Scholar
  15. 15.
    Gonzalez D, Garcia CD, Azocar M, Waller S, Alonso A, Ariceta G, Mejia N, Santos F (2011) Growth of kidney-transplanted pediatric patients treated with sirolimus. Pediatr Nephrol 26:961–966CrossRefPubMedGoogle Scholar
  16. 16.
    Höcker B, Weber LT, Feneberg R, Drube J, John U, Fehrenbach H, Pohl M, Zimmering M, Fründ S, Klaus G, Wühl E, Tönshoff B (2010) Improved growth and cardiovascular risk after late steroid withdrawal: 2-year results of a prospective, randomized trial in pediatric renal transplantation. Nephrol Dial Transpl 25:617–624CrossRefGoogle Scholar
  17. 17.
    Boobes Y, Bernieh B, Saadi H, Al Hakim MR, Abouchacra S (2010) Gonadal dysfunction and infertility in kidney transplant patients receiving sirolimus. Int Urol Nephrol 42:493–498CrossRefPubMedGoogle Scholar
  18. 18.
    Fritsche L, Budde K, Dragun D, Einecke G, Diekmann F, Neumayer HH (2004) Testosterone concentrations and sirolimus in male renal transplant patients. Am J Transplant 4:130–131CrossRefPubMedGoogle Scholar
  19. 19.
    Offner G, Toenshoff B, Höcker 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, Müller-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 86:1241–1248CrossRefPubMedGoogle Scholar
  20. 20.
    Guba M, von Breitenbuch P, Steinbauer M, Koehl G, Flegel S, Hornung M, Bruns CJ, Zuelke C, Farkas S, Anthuber M, Jauch KW, Geissler EK (2002) Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor. Nat Med 8:128–135CrossRefPubMedGoogle Scholar
  21. 21.
    Nashan B, Citterio F (2012) Wound healing complications and the use of Mammalian target of rapamycin inhibitors in kidney transplantation: a critical review of the literature. Transplantation 94:547–561CrossRefPubMedGoogle Scholar

Copyright information

© IPNA 2013

Authors and Affiliations

  • Birgitta Kranz
    • 1
  • Anne-Margret Wingen
    • 2
  • Udo Vester
    • 2
  • Jens König
    • 1
  • Peter F. Hoyer
    • 2
  1. 1.Department of General Pediatrics, Pediatric NephrologyUniversity Children’s Hospital MünsterMünsterGermany
  2. 2.Department of Pediatrics II, Children’s HospitalUniversity of Duisburg-EssenEssenGermany

Personalised recommendations