Deck 23: Excretion of Hydrophilic Toxicants and Metabolites and Kidney Toxicity

Question 1

Why does severe kidney damage always cause prerenal azotemia?

Answer 1

BUN and creatinine always increase when the kidney is not functional. The increase in nitrogen compounds such as urea and ammonia are features of prerenal azotemia.

Question 2

Why do cytotoxic cancer chemotherapy agents mainly damaging the vasculature?

Answer 2

Intravenous administration puts the highest concentrations in the local of the injection site. This is why multiple sites have to be used over time as the blood vessels succumb to the high toxicity.

Question 3

How do aminoglycoside antibiotics such as neomycin cause kidney damage?

Answer 3

The aminoglycosides are transported into proximal tubule cell luminal brush border cells and have a half-life of ~100 hours. They inhibit lysosomal enzymes to start their toxic action. Their cellular toxicity results from aminoglycoside-binding proteins (HSP73, calreticulin, CLIMP-53) that lead to stimulation of caspases and Bcl-2 signal transduction pathways. A late-stage effect of aminoglycoside toxicity is alteration of glomerular filtration. In this stage, the density and number of glomerular fenestrae decrease along with tubular backleak. Tubular obstruction occurs and mesangial platelet-activating factor is found at higher concentrations.

Question 4

Why is the loop of Henle a problematic area for a number of compounds?

Question 5

What is a marking feature of collecting duct damage?