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Kidney non-tumor

Drug related toxicity

Tacrolimus (FK506) toxicity


Reviewer: Nikhil Sangle, M.D. (see Reviewers page)
Revised: 3 September 2012, last major update September 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

See also Cyclosporine A toxicity

General
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● 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
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● 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
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● Reduce dosage

Micro description
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● 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

Micro images
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Various images

Electron microscopy images
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Tubular vacuoles represent dilatations of endoplasmic reticulum and lysosomal elements

End of Kidney non-tumor > Drug related toxicity > Tacrolimus (FK506) toxicity

Ref Updated: 7/17/12


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