American Journal of Kidney Diseases
Volume 55, Issue 2 , Pages 213-216 , February 2010

Why Do Patients Develop Proteinuria With Sirolimus? Do We Have the Answer?

  • Jeremy R. Chapman, MD

      Affiliations

    • Corresponding Author InformationAddress correspondence to Jeremy R. Chapman, MD, Department of Renal Medicine, Westmead Hospital, Westmead, Sydney, NSW 2145 Australia
    • ,
  • Gopala K. Rangan, PhD

References 

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  2. Nankivell BJ, Borrows RJ, Fung CL, O'Connell PJ, Allen RD, Chapman JR. The natural history of chronic allograft nephropathy. N Engl J Med. 2003;349(24):2326–2333
  3. Sehgal SN. Rapamune (RAPA, rapamycin, sirolimus): mechanism of action immunosuppressive effect results from blockade of signal transduction and inhibition of cell cycle progression. Clin Biochem. 1998;31(5):335–340
  4. Lee VW, Chapman JR. Sirolimus: its role in nephrology. Nephrology (Carlton). 2005;10(6):606–614
  5. Bumbea V, Kamar N, Ribes D, et al. Long-term results in renal transplant patients with allograft dysfunction after switching from calcineurin inhibitors to sirolimus. Nephrol Dial Transplant. 2005;20(11):2517–2523
  6. Kuypers DR. Benefit-risk assessment of sirolimus in renal transplantation. Drug Saf. 2005;28(2):153–181
  7. Ducloux D, Motte G, Billerey C, et al. Cyclosporin withdrawal with concomitant conversion from azathioprine to mycophenolate mofetil in renal transplant recipients with chronic allograft nephropathy: a 2-year follow-up. Transpl Int. 2002;15(8):387–392
  8. Franz S, Regeniter A, Hopfer H, Mihatsch MJ, Dickenmann M. Tubular toxicity in sirolimus- and cyclosporine-based transplant immunosupression strategies: an ancillary study from a randomized controlled trial. Am J Kidney Dis. 2010;55(2):335–343
  9. Ekberg H, Tedesco-Silva H, Demirbas A, et al. Reduced exposure to calcineurin inhibitors in renal transplantation. New Engl J Med. 2007;357(25):2562–2575
  10. Schena FP, Pascoe MD, Alberu J, et al. Conversion from calcineurin inhibitors to sirolimus maintenance therapy in renal allograft recipients: 24-month efficacy and safety results from the CONVERT trial. Transplantation. 2009;87(2):233–242
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  12. Russ G, Campbell S, Chadban S, et al. Members of the Wyeth Australia Transplant Advisory Board Sirolimus: an expert panel guide on who and how to convert renal transplant patients from a CNI- to sirolimus-based regimen, including management of key adverse events (version 2). October 2006;
  13. Augustine JJ, Bodziak KA, Hricik DE. Use of sirolimus in solid organ transplantation. Drugs. 2007;67(3):369–391
  14. Gutierrez-Dalmau A, Campistol JM. The role of proliferation signal inhibitors in post-transplant malignancies. Nephrol Dial Transplant. 2007;22(suppl 1):i11–i16
  15. Campistol JM, Eris J, Oberbauer R, et al. Sirolimus therapy after early cyclosporine withdrawal reduces the risk for cancer in adult renal transplantation. J Am Soc Nephrol. 2006;17(2):581–589
  16. Vollenbroker B, George B, Wolfgart M, Saleem MA, Pavenstadt H, Weide T. mTOR regulates expression of slit diaphragm proteins and cytoskeleton structure in podocytes. Am J Physiol. 2009;296(2):F418–F426
  17. Letavernier E, Bruneval P, Vandermeersch S, et al. Sirolimus interacts with pathways essential for podocyte integrity. Nephrol Dial Transplant. 2008;24(2):630–638
  18. Lieberthal W, Fuhro R, Andry C, Patel V, Levine JS. Rapamycin delays but does not prevent recovery from acute renal failure: role of acquired tubular resistance. Transplantation. 2006;82(1):17–22
  19. 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. 2001;281(4):F693–F706
  20. Smith KD, Wrenshall LE, Nicosia RF, et al. Delayed graft function and cast nephropathy associated with tacrolimus plus rapamycin use. J Am Soc Nephrol. 2003;14(4):1037–1045
  21. Straathof-Galema L, Wetzels JF, Dijkman HB, Steenbergen EJ, Hilbrands LB. Sirolimus-associated heavy proteinuria in a renal transplant recipient: evidence for a tubular mechanism. Am J Transplant. 2006;6(2):429–433

PII: S0272-6386(09)01572-8

doi: 10.1053/j.ajkd.2009.12.003

American Journal of Kidney Diseases
Volume 55, Issue 2 , Pages 213-216 , February 2010

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