Renal - Review Questions

Question 1

analgesic nephropathy

Answer 1

chronic consumption of combinations of NSAIDs and/or APAP (more than 3 years)

papillary necrosis with chronic interstitial nephritis.

Klaassen, Curtis D.. Casarett & Doull’s Toxicology: The Basic Science of Poisons, 9th Edition (p. 786). McGraw-Hill Education. Kindle Edition.

Question 2

aminoglycosides

Answer 2

S1 and S2 segments

phospholipidosis due to inhibition of lysosomal hydrolases

Question 3

radioconstrast agents

Answer 3

third most common cause of AKI

altered renal perfusion due to high viscosity and direct effects on endothelial cells

Question 4

NGAL

Answer 4

distal nephron damage

Question 5

Halogenated hydrocarbons (e.g. chloroform)

Answer 5

cytochrome P450 metabolism -> reactive intermediate that covalently binds to nucelophilic groups on macromolecules

Question 6

haloalkenes (tetrafluorethylene)

Answer 6

proximal tubular necrosis (S3 segment)

Question 7

KIM-1

Answer 7

proximal tubular damage

Question 8

charge and glomerular filtration

Answer 8

Filtration of anionic molecules tends to be restricted compared to that of neutral or cationic molecules of the same size; this is primarily due to the charge-selective properties of the GBM

Klaassen, Curtis D.; Watkins, John B.. Casarett & Doull’s Essentials of Toxicology, Third Edition (Lange) . McGraw-Hill Education. Kindle Edition.

Question 9

cyclosporine

Answer 9

acute vasculopathy

chronic glomerular sclerosis and tubular atrophy (vasoconstriction)

The decrease in RBF and GFR is related to marked vasoconstriction induced by cyclosporine, and it is probably produced by a number of factors:

including an imbalance in vasoconstrictor and vasodilatory prostaglandin production,

increased production of the vasoconstrictor thromboxane and endothelin,

and activation of the renin-angiotensin system.

Klaassen, Curtis D.. Casarett & Doull’s Toxicology: The Basic Science of Poisons, 9th Edition (p. 788). McGraw-Hill Education. Kindle Edition.

Question 10

Depleted uranium

Answer 10

renal tubular necrosis

Question 11

Proximal tubule

Answer 11

S1 (pars convoluta): vascular lysosomal system

S2: the end of the convoluted segment and the initial portion of the straight segment.

S3 (pars recta): catabolism, glutathione transport, GGT activity

Question 12

indomethacin

Answer 12

papillary necrosis

Question 13

Acetaminophen

Answer 13

acute proximal tubular necrosis

biotransformation at recommended doses generally via conjugation to sulfate or glucuronic acid and excreted in urine (Phase I not needed)

High doses saturate conjugation capacity -> CYP2E1 biotransformation -> NAPQI

Question 14

Von-Hippel Lindau (VHL) germline mutations

Answer 14

target hypoxia inducible factor (HIF) proteins for degradation

loss of VHL results in increased HIF1 expression -> neovascularization

loss of both alleles required for tumorigenesis -> retinal and brain hemangioblastomas, renal clear cell carcinomas, pheochromocytomas, pancreatic neuroendocrine tumors, endolymphatic sac tumors

mutations can be induced by trichloroethylene (TCE)