Vulnerability of the kidney

The vulnerability of the kidney to cisplatin is almost certainly linked to its primary role in the excretion of the drug. The P3 segment of the proximal tubule is particularly vulnerable to it. The cause of renal cell death induced by cisplatin is unknown, but mounting evidence points to its genotoxic effect. In cisplatin nephrotoxicity, as in other forms of nephrotoxic renal damage, reduced renal blood flow and diminished renal conservation of water are common physiologic derangements. 

Studies in animals revealed that hexachlorobutadiene causes damage to the proximal tubules of the kidney and, to a lesser extent, to the liver. Accordingly, people with preexisting kidney and liver damage may have compromised organ functions and are expected to be more vulnerable to chemical insult than people with normal kidney and liver functions. Infants are more likely to be... 

Brezis M, Rosen S, Silva P, and Epstein ELI. Selective vulnerability of the medullary thick ascending limb to anoxia in the isolated perfused rat kidney.The Journal of Clinical Investigation 73 182-190,1984. 

Jamall IS, Naik M, Sprowls JJ, et al. 1989. A comparison of the effects of dietary cadmium on heart and kidney antioxidant enzymes Evidence for the greater vulnerability of the heart to cadmium toxicity. J Appl Toxicol 9(5) 339-345. 

The kidney is known to be particularly vulnerable to the toxic effects of heme and hemoglobin in disseminated intravascular hemolysis, and... 

Sensitive eye tissue is vulnerable to amines. These compounds can have systemic effects on many organs in the body. Necrosis of the liver and kidneys can occur, and exposed lungs can exhibit hemorrhage and edema. The immune system may become sensitized to amines. 

In addition, alternative factors may modulate the direct cellular toxicity of AmB. For example, maintaining kidney epithelial cells in an acidic environment enhances the permeability changes induced hy AmB in an irreversible fashion [82]. This suggests that the low pH characteristic of the distal tubule makes those cells more vulnerable to the toxic effects of AmB, and may explain the protective effect of alkalinizing agents... 

Further evidence that links the kidney s vulnerability to its role in cisplatin transport is provided by autoradiographic studies that show greater uptake of radiolabeled cisplatin in the S3 segments of the proximal nephron [13]. As the S3 segment of the proximal tubule is the principle site of cell toxicify of cisplatin and contains the most platinum, these studies provide further evidence that the particular vulnerability of this cell type depends on its ability to accumulate cisplatin. 

The kidneys are particularly vulnerable to effects of noxious agents because of their high perfusion rate. 

Because of their role as filtering organs, the kidneys are vulnerable to attack by a wide variety of xenobiotics, including halogenated hydrocarbons, aromatic hydrocarbons, ketones, glycol ethers, pesticides, heavy metals, and metabolites of other xenobiotics. 

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