Home   Chapter Home   Jobs   Conferences   Fellowships   Books



Advertisement

Kidney non-tumor

Drug related toxicity

Cyclosporin A toxicity


Reviewer: Nikhil Sangle, M.D. (see Reviewers page)
Revised: 10 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Anticalcineurins (cyclosporine A and tacrolimus) were discovered in late 70's; constitute a basic component of all immunosuppressive protocols to control transplant rejection for solid organ graft recipients
● Nephrotoxicity is major concern (Clin J Am Soc Nephrol 2009;4:481)
● Nephrotoxic, hepatotoxic and neurotoxic
● Also causes gingival hyperplasia, hypertrichosis and lymphoma
● Nephrotoxicity is dose related, occurs in 3%

Functional toxicity
=========================================================================

● Mild decrease in renal function and increase in serum creatinine, hypertension in 50%, reversible if dosage lowered and no morphologic changes in kidney
● Toxicity due to alteration in intrarenal hemodynamics (vasoconstrictive phenomenon)

Acute tubular toxicity
=========================================================================

● Similar to functional toxicity but more severe
● Microscopic changes include vacuoles in proximal tubules (due to dilated endoplasmic reticulum with giant mitochondria, large lysosomes) and microcalcifications
● Also arteriolar smooth muscle cell degeneration, endothelial cell swelling, intimal thickening, variable hyaline or mucoid deposits which narrow lumen
● Dose dependent and reversible

Thrombotic microangiopathy
=========================================================================

● Resembles hemolytic uremic syndrome
● Occurs days to weeks after transplantation
● Glomeruli and vessels show thrombotic microangiopathy with platelet and fibrin thrombi and minimal inflammatory infiltrate
● Poor prognosis
● In one study, most common cause was antibody mediated rejection, not cyclosporine toxicity (Am J Transplant 2010;10:1804)

Chronic toxicity
=========================================================================

● Hypertension and slow progression to renal failure
● Arterioles show nodular or diffuse hyalinosis of vessel walls or mucoid thickening of intima, leading to luminal narrowing
● Also diffuse interstitial fibrosis and tubular atrophy
● Early glomerular changes are aggregates of platelets and fibrin
● Late changes are focal and segmental glomerulosclerosis or global scarring
● Changes are irreversible

Micro images
=========================================================================



Various images

           
Expression of P-glycoprotein, endothelin1, RANTES, MCP1 mRNA (ISH)

   
Allograft treated with cyclosporine A


Classic features of calcineurin inhibitor toxicity (cyclosporine and tacrolimus)

End of Kidney non-tumor > Drug related toxicity > Cyclosporin A toxicity

Ref Updated: 7/10/12


This information is intended for physicians and related personnel, who understand that medical information is often imperfect, and must be interpreted in the context of a patient's clinical data using reasonable medical judgment. This website should not be used as a substitute for the advice of a licensed physician.

All information on this website is protected by copyright of PathologyOutlines.com, Inc. Information from third parties may also be protected by copyright. Please contact us at copyrightPathOut@gmail.com with any questions (click here for other contact information).