Kidney Toxicity Flashcards
Acute Kidney Injury criteria: (3)
Increase serum creatine to 1.5 times baseline
Decreased urine volume
Decreased in eGFR
Biomarkers of kidney toxicity
- urinary proteins with enzymatic activities
- Proteinuria
- Kidney injury molecule (KIM-1)
- Neutrophil gelatinase-associated lipocalin (NGAL)
- Cytokines
- Clusterin
- Type IV collagen
- Osteopontin
Chronic kidney disease symptoms
decreased eGFR
increased albumin: creatine ration
how many % of cardiac output does kidney receive?
20-25%
Three toxic form of Hg
Elemental, Organic, Inorganic
Absorbed by lugs following inhalation, can cross blood brain barrier
Element mercury
after absorption, accumlates in kidney
Inorganic mercury
most readily absorbed, distributes especially to the brain
Organic mercury
How does binding of Hg occur in the body?
divalent mercuric ion (Hg2+) binds to sulfhydryl group in protein (-SH)
Toxic effects of mercury
- Increase oxidatve stress
- Disruption of microtubule formation
- Interference with protein synthesis
- Interference with DNA replication
- Interference with Ca homeostasis
Example of Halogenated hydrocarbon
CCl3
Halogenated hydrocarbon toxicity mechanisms
linked to its metabolism by renal cytochrome P450.
Formation of reactive intermediate which binds covalently to nucleophilic groups on cellular macromolecules
most reported poisoning cases among analgesics
Acetaminophen
Nephrotoxicity of Acetaminophen
- Proximal tubular necrosis
- Increases in blood urea level and plasma creatine
- Decreases in GFR and clearance of para-aminohippurate
- Increases in the fractional excretion of water, sodium and potassium
- Increases in urinary glucose, protein, and brush border enzymes
Antidote of acetominophen
N-acetylcysteine
Cytochrome P450 oxidation pathway will produce _____ which is a toxic intermediate
NAPQI
Examples of NSADIS
ibuprofen, naproxen, indomethacin, cyclooxygenase-2 inhibitors
Mechanisms of NSAIDs toxicity
Inhibition of prostaglandin synthesis and results in vasoconstriction which leads to reduced renal blood flow.
Nephrotoxicity antibiotics
Aminoglycoside
Example of aminoglycoside
Gentamycin
Aminoglysocide used for gram ___ bacteria
negative
Mechanisms of gentamycin toxicity
Filtered in the glomerulus and entered the tubular lumen
Taken up by proximal tubular cells and in vesicles
Fused with lysosomes inside the cell
Destabilising lysosomes, causing it to rupture and release its hydrolytic enzymes which cause damage within the cell
Gentamycin also can cause direct damage on mitochondria
