Pharmacological aspects of nephrotoxicity

  • Marisa D. Covington
  • Rick G. Schnellmann

Because the kidney is vital to total body homeostasis, a toxic insult to the kidney can have profound effects – an insult of sufficient severity can permanently damage renal tissue, necessitating chronic dialysis or kidney transplantation. Such susceptibility to various toxicants is due to several functional properties of the kidney. First, the kidney receives approximately one-quarter of the total body blood flow to support renal function, including glomerular filtration, permitting the delivery of high levels of toxicants. The absorption of water and solutes along the nephron concentrates the tubular fluid, thereby exposing tubular epithelial cells to greater concentrations of toxicants.

The high metabolic rate and work load of renal cells increases its susceptibility to toxicants. Furthermore, the kidney possesses biotransformation enzymes that can result in formation of toxic metabolites and reactive intermediates which can damage renal macromolecules. Because the nephron has specialized transporters for reabsorption and excretion, toxicants can enter and accumulate within renal cells, leading to nephrotoxicity. Finally, the unique functions of the varied segments along the nephron impart different susceptibilities to toxicants in the kidney, complicating the potential toxicities and subsequent renal damage via a variety of mechanisms. In this chapter, we will review some of these sites and mechanisms of nephrotoxicity.


Acute Renal Failure Hepatocyte Growth Factor Tubular Epithelial Cell Acute Tubular Necrosis Renal Tubular Cell 


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© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Marisa D. Covington
    • 1
  • Rick G. Schnellmann
    • 1
  1. 1.Medical University of South CarolinaCharlestonUSA

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