American Journal of Kidney Diseases
Volume 55, Issue 2 , Pages 335-343 , February 2010

Tubular Toxicity in Sirolimus- and Cyclosporine-Based Transplant Immunosuppression Strategies: An Ancillary Study From a Randomized Controlled Trial

  • Stefan Franz, MD

      Affiliations

    • Clinic for Transplantation Immunology and Nephrology, University Hospital, Basel, Switzerland
    • ,
  • Axel Regeniter, MD

      Affiliations

    • Laboratory Medicine, University Hospital, Basel, Switzerland
    • ,
  • Helmut Hopfer, MD

      Affiliations

    • Institute of Clinical Pathology, University Hospital, Basel, Switzerland
    • ,
  • Michael Mihatsch, MD

      Affiliations

    • Institute of Clinical Pathology, University Hospital, Basel, Switzerland
    • ,
  • Michael Dickenmann, MD

      Affiliations

    • Clinic for Transplantation Immunology and Nephrology, University Hospital, Basel, Switzerland
    • Corresponding Author InformationAddress correspondence to Michael Dickenmann, MD, Clinic for Transplantation Immunology and Nephrology, University Hospital, Petersgraben 4, CH-4031 Basel, Switzerland

Received 8 December 2008 ,Accepted 9 September 2009.

References 

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  2. Braun WE. Renal transplantation: basic concepts and evolution of therapy. J Clin Apher. 2003;18(3):141–152
  3. Sehgal SN, Baker H, Vezina C. Rapamycin (AY-22,989), a new antifungal antibiotic (II. Fermentation, isolation and characterization). J Antibiot (Tokyo). 1975;28(10):727–732
  4. Calne RY, Collier DS, Lim S, et al. Rapamycin for immunosuppression in organ allografting. [letter] Lancet. 1989;2(8656):227
  5. DiJoseph JF, Mihatsch MJ, Sehgal SN. Renal effects of rapamycin in the spontaneously hypertensive rat. Transpl Int. 1994;7(2):83–88
  6. Kahan BD. Efficacy of sirolimus compared with azathioprine for reduction of acute renal allograft rejection: a randomised multicentre study (The Rapamune US Study Group). Lancet. 2000;356(9225):194–202
  7. Podder H, Stepkowski SM, Napoli KL, et al. Pharmacokinetic interactions augment toxicities of sirolimus/cyclosporine combinations. J Am Soc Nephrol. 2001;12(5):1059–1071
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  10. McTaggart RA, Gottlieb D, Brooks J, et al. Sirolimus prolongs recovery from delayed graft function after cadaveric renal transplantation. Am J Transplant. 2003;3(4):416–423
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  12. Diekmann F, Gutierrez-Dalmau A, Lopez S, et al. Influence of sirolimus on proteinuria in de novo kidney transplantation with expanded criteria donors: comparison of two CNI-free protocols. Nephrol Dial Transplant. 2007;22(8):2316–2321
  13. Franco AF, Martini D, Abensur H, Noronha IL. Proteinuria in transplant patients associated with sirolimus. Transplant Proc. 2007;39(2):449–452
  14. Maachi M, Fellahi S, Regeniter A, et al. Patterns of proteinuria: urinary sodium dodecyl sulfate electrophoresis versus immunonephelometric protein marker measurement followed by interpretation with the knowledge-based system MDI-LabLink. Clin Chem. 2004;50(10):1834–1837
  15. Nickeleit V, Zeiler M, Gudat F, Thiel G, Mihatsch MJ. Detection of the complement degradation product C4d in renal allografts: diagnostic and therapeutic implications. J Am Soc Nephrol. 2002;13(1):242–251
  16. Solez K, Colvin RB, Racusen LC, et al. Banff 07 classification of renal allograft pathology: updates and future directions. Am J Transplant. 2008;8(4):753–760
  17. Nickeleit V, Zeiler M, Gudat F, Thiel G, Mihatsch MJ. Histological characteristics of interstitial renal allograft rejection. Kidney Blood Press Res. 1998;21(2-4):230–232
  18. Groth CG, Backman L, Morales JM, et al. Sirolimus (rapamycin)-based therapy in human renal transplantation: similar efficacy and different toxicity compared with cyclosporine (Sirolimus European Renal Transplant Study Group). Transplantation. 1999;67(7):1036–1042
  19. Kreis H, Cisterne JM, Land W, et al. Sirolimus in association with mycophenolate mofetil induction for the prevention of acute graft rejection in renal allograft recipients. Transplantation. 2000;69(7):1252–1260
  20. Morales JM, Wramner L, Kreis H, et al. Sirolimus does not exhibit nephrotoxicity compared to cyclosporine in renal transplant recipients. Am J Transplant. 2002;2(5):436–442
  21. Guder WG, Ivandic M, Hofmann W. Physiopathology of proteinuria and laboratory diagnostic strategy based on single protein analysis. Clin Chem Lab Med. 1998;36(12):935–939
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  23. Bergamaschi E, Mutti A, Alinovi R, et al. Tubular reabsorption of proteins is a selective process (Evidence from selected nephrotoxicity models). Contrib Nephrol. 1993;101:92–98
  24. Olgaard K, Madsen S, Lund B, Sorensen OH. Pathogenesis of hypophosphatemia in kidney necrograft recipients: a controlled trial. Adv Exp Med Biol. 1980;128:255–261
  25. Graf H, Kovarik J, Stummvoll HK, Wolf A, Pinggera WF. Handling of phosphate by the transplanted kidney. Proc Eur Dial Transplant Assoc. 1979;16:624–629
  26. Schwarz C, Bohmig GA, Steininger R, Mayer G, Oberbauer R. Impaired phosphate handling of renal allografts is aggravated under rapamycin-based immunosuppression. Nephrol Dial Transplant. 2001;16(2):378–382
  27. Lieberthal W, Fuhro R, Andry CC, et al. Rapamycin impairs recovery from acute renal failure: role of cell-cycle arrest and apoptosis of tubular cells. Am J Physiol Renal Physiol. 2001;281(4):F693–F706
  28. Lawsin L, Light JA. Severe acute renal failure after exposure to sirolimus-tacrolimus in two living donor kidney recipients. Transplantation. 2003;75(1):157–160

 Originally published online as doi:10.1053/j.ajkd.2009.09.004 on November 18, 2009.

 Trial registration: www.clinicaltrials.gov; study number: NCT00812123.

PII: S0272-6386(09)01187-1

doi: 10.1053/j.ajkd.2009.09.004

American Journal of Kidney Diseases
Volume 55, Issue 2 , Pages 335-343 , February 2010

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