Kidney nontumor
Drug related toxicity
Cyclosporin A toxicity

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

Revised: 21 March 2018, last major update January 2013

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

PubMed Search: Cyclosporin A toxicity [title]

Cite this page: Sangle, N. Cyclosporin A toxicity. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/kidneycyclosporinA.html. Accessed June 19th, 2018.
Definition / 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
Microscopic (histologic) images

Images hosted on other servers:

Various images

Allograft treated with cyclosporine A


Classic features of
calcineurin inhibitor
toxicity (cyclosporine
and tacrolimus)