Kidney Toxicity Flashcards
Why is the kidney exposed to high levels of drugs and toxicants? (2)
- By virtue of the concentrating effect of the glomerular filtrate in the LoH and CD.
- The kidney itself has the capacity to conduct drug metabolism, which can lead to the activation of pro-toxicants
What is the result of numerous toxicants and drugs on the kidney?
They can cause mitochondrial dysfunction via compromised ETC activity or ATP production, leading to apoptosis or necrosis
What is acute kidney injury (AKI) characterized by?
Abrupt decline in GFR with resulting azotemia (increased nitrogen wastes in the blood)
Are all renal injuries the same?
No, they span a spectrum from minimal elevation in serum creatinine to anuric renal failure
Function of the renal tubules is highly dependent on what?
total epithelial cell integrity
When drugs compromise total epithelial integrity of the renal tubule, what two things can happen?
- Diminished GFR: epithelial compromise→ opportunity for back leaking of renal filtrate→reduced GFR
- Tubular Obstruction: compromise→ detached cells can aggregate in tubule or adhere to other epithelial cells downstream→tubular obstruction
Inflammatory cells are attracted to what? Under what conditions? What does this result in?
Where there is low O2 tension, inflammatory cells are attracted by the release of numerous chemokines→creates pro-inflammatory situation with neutrophil adhesion to underlying tubular structures
After exposure to a toxicant , one or more of what possible mechanisms may contribute to reduced GFR?
- Renal Vasoconstriction→ leading to pre-renal azotemia and obstruction due to precipitation of a drug or endogenous compound w/in the kidney
- Intarenal factors include: direct tubular obstruction and dysfunction→tubular back-leak and increased tubular pressure
- Alterations in the levels of various vasoactive mediators→decreased renal perfusion pressure or afferent arteriolar tone and increased efferent arteriole(??make sure eff and aff are right??) tone→decreased glomerular hydrostatic pressure
After an acute injury, what happens to damaged kidney cells? What happens to the rest of the tissue?
They are repaired or undergo apoptosis, if unviable.
The remaining tissue undergoes a compensatory hypertrophy and proliferation to reconstruct the functional integrity of the glomerulus and nephron
Pre-renal AKI?
reduced blood supply to the kidney; GFR falls as a consequence
Crystalluria?
precipitation in tubules causing obstruction
Tubular Toxicity?
damage to and loss of integrity of tubules
Endothelial KI’s?
endothelial pro-inflammatory condition with detachment, release of chemotactic factors, and reduced NO (vasodilator) production
Glomerulopathy?
damage to the glomerulus leading to loss of integrity and abrupt onset of hematuria, proteinuria, edema, and hypertension
Interstitial nephritis?
inflammation of the spaces between the renal tubules