Kidney nontumor
Drug related toxicity
Tacrolimus (FK506) toxicity

Author: Nikhil Sangle, M.D. (see Authors page)

Revised: 26 March 2018, last major update September 2012

Copyright: (c) 2003-2018, PathologyOutlines.com, Inc.

PubMed Search: Tacrolimus (FK506) toxicity [title] pathology

Related topics: Cyclosporin A toxicity
Cite this page: Sangle, N. Tacrolimus (FK506) toxicity. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/kidneytacrolimus.html. Accessed November 15th, 2018.
Definition / general
  • Immunosuppressive drug used frequently in renal transplants, effect may be mediated by binding to FKBP12, a cytosolic protein
  • FKBP12/FK506 binds to and inactivates calcineurin (a serine / threonine phosphatase), which inhibits calcium and calmodulin dependent B and T cell responses by blocking NFAT-mediated transcription
Clinical features
  • Systemic levels of tacrolimus, if kept within a relatively narrow target window, may not be associated with nephrotoxicity (Transplant Proc 2009;41:3393)
  • The presence of rejection does not rule out Tacrolimus or Cyclosporine toxicity
  • Red cell exchange transfusion may be useful for severe toxicity (Pediatr Nephrol 2011;26:2245)
  • Although mechanism of action is similar to cyclosporine A, mechanisms causing nephrotoxicity may differ (J Proteomics 2011;75:677)
Treatment
  • Reduce dosage
Microscopic (histologic) description
  • Toxicity (in 1%) is similar to cyclosporin A at level of renal vascular endothelium, leading to fibrin thrombi in glomerular capillaries and afferent arterioles (Am J Surg Pathol 1996;20:306, Am J Surg Pathol 1993;17:60)
  • May also cause arteriolar hyalinosis and splitting / reduplication of glomerular basement membrane
Microscopic (histologic) images

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Various images

Electron microscopy images

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Tubular vacuoles represent
dilatations of endoplasmic
reticulum and lysosomal elements