Cellular mechanisms of nephrotoxicity

  • Istvan Arany
  • Gur P. Kaushal
  • Didier Portilla
  • Judit Megyesi
  • Peter M. Price
  • Robert L. Safirstein

The changes in renal epithelial morphology that accompany acute kidney injury are often subtle. At least four cellular fates can be identified in acute kidney injury: cells may be necrotic; cells may become apoptotic; they may replicate and divide; or they may appear indifferent to the stress (Figure 1). Frank necrosis, as is often seen experimentally, is not prominent in the vast majority of human cases. Necrosis is usually patchy, involving small clusters of cells, sometimes resulting in small areas of denuded basement membrane. Less obvious injury is more often noted, including loss of brush borders, flattening of the epithelium, intratubular cast formation, and dilatation of the lumen. While proximal tubules show many of theses changes, injury to the distal nephron can also be demonstrated when human biopsy material is closely examined. The distal nephron is also the site of obstruction by desquamated cells and cellular debris.

Necrosis is a catastrophic breakdown of regulated cellular homeostasis and is accompanied by massive tissue damage leading to rapid collapse of internal homeostasis of the cell [1]. It is characterized by cell swelling with early loss of plasma-membrane integrity, major alterations of the organelles, and swelling of the nucleus with flocculation of the chromatin. Affected cells rupture and the cellular components spill into the surrounding tissue space evoking an inflammatory response. Apoptosis is also a feature of nephrotoxic injury and a distinction can be made between necrosis and apoptosis based on morphological criteria (Table 1).


Acute Kidney Injury Proximal Tubule Cell Distal Nephron Renal Tubular Epithelial Cell Thick Ascend Limb 
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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Istvan Arany
    • 1
  • Gur P. Kaushal
    • 1
  • Didier Portilla
    • 1
  • Judit Megyesi
    • 1
  • Peter M. Price
    • 1
  • Robert L. Safirstein
    • 1
  1. 1.Central Arkansas Veterans Health Care SystemLittle RockUSA

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