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DABT 2025 > Kidney Toxicity > Flashcards

Kidney Toxicity Flashcards

(51 cards)

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1
Q

What are common toxic agents for kidney toxicity?

A

Mercury(II) chloride (HgCl2), cisplatin, gentamicin, aristolochic acid, ochratoxin A, ethylene glycol, cadmium.

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2
Q

What is the mechanism of HgCl2-induced kidney toxicity?

A

Accumulates in proximal tubules, causes oxidative stress and cell death.

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3
Q

What is the mechanism of cisplatin kidney toxicity?

A

Generates ROS, causes DNA damage and apoptosis in renal tubular cells.

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4
Q

What is the mechanism of gentamicin kidney toxicity?

A

Accumulates in lysosomes of proximal tubules, disrupts phospholipid metabolism.

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5
Q

What are biomarkers for kidney toxicity?

A

Elevated serum creatinine, BUN, urinary KIM-1, NAG; decreased GFR.

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6
Q

What are testing methods for kidney toxicity?

A

Serum creatinine/BUN tests, urinalysis (proteinuria), renal biopsy.

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7
Q

What are endpoints for kidney toxicity?

A

Acute kidney injury (AKI), chronic kidney disease (CKD), renal failure.

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8
Q

How does ethylene glycol cause kidney toxicity?

A

Metabolized to oxalate crystals, obstructing renal tubules.

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9
Q

What is the role of in kidney toxicity?

A

Accumulates in proximal tubules, causes tubular proteinuria and Fanconi syndrome.

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10
Q

How does aristolochic acid cause kidney toxicity?

A

Forms DNA adducts in renal cells, leading to urothelial carcinoma.

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11
Q

How does cisplatin mechanistically cause nephrotoxicity? (Domain II)

A

Cisplatin forms DNA adducts and generates ROS, targeting proximal tubule cells, causing apoptosis and acute kidney injury (DABT_Study_Notes.xlsx, Kidney Tox; Web: NIH, 2025).

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12
Q

What is the renal target of aminoglycoside antibiotics like gentamicin? (Domain II)

A

Aminoglycosides target proximal tubule cells, accumulating via megalin-mediated endocytosis, disrupting lysosomal function, causing tubular necrosis (DABT_Study_Notes.xlsx, Kidney Tox; Web: PubMed, 2024).

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13
Q

How does mercury (HgCl2) induce kidney toxicity? (Domain II)

A

Mercury binds sulfhydryl groups, targeting proximal tubule S3 segment, causing ROS-mediated apoptosis and acute tubular necrosis (DABT_Study_Notes.xlsx, Kidney Tox; Principles & Mechanisms).

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14
Q

What mechanism underlies cadmium’s chronic nephrotoxicity? (Domain II)

A

Cadmium binds metallothionein, accumulating in proximal tubules, causing ROS and mitochondrial dysfunction, leading to tubular proteinuria (DABT_Study_Notes.xlsx, Kidney Tox; Chemical Carcinogenesis).

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15
Q

How does aristolochic acid cause nephrotoxicity and carcinogenicity? (Domain II)

A

Aristolochic acid forms DNA adducts (AL-DNA), targeting proximal tubules, causing interstitial nephropathy and urothelial carcinoma (DABT_Study_Notes.xlsx, Kidney Tox; Web: IARC, 2024).

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16
Q

What is the renal target of ochratoxin A toxicity? (Domain II)

A

Ochratoxin A targets proximal tubule cells, inhibiting mitochondrial respiration and causing oxidative stress, leading to tubular degeneration (DABT_Study_Notes.xlsx, Kidney Tox; Web: NIH, 2025).

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17
Q

How does cyclosporine A mechanistically cause nephrotoxicity? (Domain II)

A

Cyclosporine A induces vasoconstriction via endothelin-1, targeting afferent arterioles, causing ischemia and chronic tubulointerstitial fibrosis (DABT_Study_Notes.xlsx, Kidney Tox; Web: PubMed, 2024).

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18
Q

What mechanism does ethylene glycol use to cause kidney toxicity? (Domain II)

A

Ethylene glycol metabolites (glycolic acid, oxalate) form calcium oxalate crystals, targeting renal tubules, causing obstruction and acute kidney injury (DABT_Study_Notes.xlsx, Kidney Tox; Principles & Mechanisms).

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19
Q

How does acetaminophen overdose affect the kidneys? (Domain II)

A

Acetaminophen’s metabolite NAPQI depletes glutathione, targeting proximal tubules, causing oxidative stress and acute tubular necrosis (DABT_Study_Notes.xlsx, Kidney Tox; Principles & Mechanisms).

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20
Q

What is the renal target of amphotericin B toxicity? (Domain II)

A

Amphotericin B targets distal tubule cells, forming membrane pores, causing electrolyte imbalances and tubular dysfunction (DABT_Study_Notes.xlsx, Kidney Tox; Web: FDA, 2024).

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21
Q

How does lead (Pb) mechanistically cause nephrotoxicity? (Domain II)

Study These Flashcards
A

Lead disrupts mitochondrial function and generates ROS, targeting proximal tubules, causing Fanconi syndrome and chronic nephropathy (DABT_Study_Notes.xlsx, Kidney Tox; Principles & Mechanisms).

22
Q

What mechanism underlies NSAID-induced nephrotoxicity (e.g., ibuprofen)? (Domain II)

Study These Flashcards
A

NSAIDs inhibit COX, reducing prostaglandin synthesis, targeting glomeruli, causing vasoconstriction and acute kidney injury (DABT_Study_Notes.xlsx, Kidney Tox; Web: NIH, 2025).

23
Q

How does tacrolimus cause kidney toxicity? (Domain II)

Study These Flashcards
A

Tacrolimus inhibits calcineurin, targeting afferent arterioles, causing vasoconstriction and chronic interstitial fibrosis (DABT_Study_Notes.xlsx, Kidney Tox; Web: PubMed, 2024).

24
Q

What is the renal target of lithium toxicity? (Domain II)

Study These Flashcards
A

Lithium targets distal tubules and collecting ducts, disrupting aquaporin-2, causing nephrogenic diabetes insipidus (DABT_Study_Notes.xlsx, Kidney Tox; Web: NIH, 2025).

25
How does chloroform induce nephrotoxicity in male mice? (Domain II)
Chloroform’s metabolite phosgene forms protein adducts, targeting proximal tubules, causing necrosis and renal tumors (DABT_Study_Notes.xlsx, Kidney Tox; Chemical Carcinogenesis).
26
What mechanism does melamine use to cause kidney toxicity? (Domain II)
Melamine forms crystals with cyanuric acid, targeting renal tubules, causing obstruction and acute kidney injury (DABT_Study_Notes.xlsx, Kidney Tox; Web: FDA, 2024).
27
How does hexachlorobutadiene cause nephrotoxicity? (Domain II)
Hexachlorobutadiene’s glutathione conjugate is cleaved to a reactive thiol, targeting proximal tubule S3 segment, causing necrosis (DABT_Study_Notes.xlsx, Kidney Tox; Web: PubMed, 2024).
28
What is the renal target of carbon tetrachloride (CCl4) toxicity? (Domain II)
CCl4 targets proximal tubules, forming reactive trichloromethyl radicals, causing lipid peroxidation and tubular necrosis (DABT_Study_Notes.xlsx, Kidney Tox; Principles & Mechanisms).
29
How does 2,4-dichlorophenoxyacetic acid (2,4-D) affect the kidneys? (Domain II)
2,4-D disrupts mitochondrial function, targeting proximal tubules, causing oxidative stress and tubular injury (DABT_Study_Notes.xlsx, Kidney Tox; Web: EPA, 2024).
30
What mechanism underlies uranium’s nephrotoxicity? (Domain II)
Uranium binds phosphate groups, targeting proximal tubules, causing mitochondrial dysfunction and acute tubular necrosis (DABT_Study_Notes.xlsx, Kidney Tox; Web: NIH, 2025).
31
How does gentamicin’s nephrotoxicity differ from cisplatin’s? (Domain II)
Gentamicin disrupts lysosomal function via megalin uptake, while cisplatin forms DNA adducts and ROS, both targeting proximal tubules (DABT_Study_Notes.xlsx, Kidney Tox; Web: PubMed, 2024).
32
What is the renal target of methotrexate toxicity? (Domain II)
Methotrexate precipitates in renal tubules, causing obstruction and acute kidney injury, targeting distal tubules (DABT_Study_Notes.xlsx, Kidney Tox; Web: NIH, 2025).
33
How does ifosfamide cause nephrotoxicity? (Domain II)
Ifosfamide’s metabolite chloroacetaldehyde disrupts mitochondrial function, targeting proximal tubules, causing Fanconi syndrome (DABT_Study_Notes.xlsx, Kidney Tox; Web: PubMed, 2024).
34
What mechanism does ochratoxin A use to promote renal carcinogenicity? (Domain II)
Ochratoxin A forms DNA adducts and induces oxidative stress, targeting proximal tubules, leading to renal cell carcinoma (DABT_Study_Notes.xlsx, Kidney Tox; Chemical Carcinogenesis).
35
How does aristolochic acid’s nephrotoxicity lead to urothelial cancer? (Domain II)
Aristolochic acid’s AL-DNA adducts cause p53 mutations, targeting urothelial cells, leading to carcinoma (DABT_Study_Notes.xlsx, Kidney Tox; Web: IARC, 2024).
36
What is the renal target of cyclosporine A’s chronic toxicity? (Domain II)
Cyclosporine A targets tubulointerstitial tissue, causing fibrosis via TGF-β upregulation (DABT_Study_Notes.xlsx, Kidney Tox; Web: PubMed, 2024).
37
How does cadmium’s nephrotoxicity manifest in humans? (Domain II)
Cadmium causes tubular proteinuria (β2-microglobulin excretion) by damaging proximal tubule cells via ROS (DABT_Study_Notes.xlsx, Kidney Tox; Web: NIH, 2025).
38
What mechanism underlies mercury’s acute tubular necrosis? (Domain II)
Mercury binds sulfhydryl groups on enzymes, targeting proximal tubule S3, causing mitochondrial collapse and necrosis (DABT_Study_Notes.xlsx, Kidney Tox; Principles & Mechanisms).
39
How does ethylene glycol’s oxalate crystals affect renal function? (Domain II)
Oxalate crystals obstruct tubules, targeting proximal and distal tubules, causing hydronephrosis and acute renal failure (DABT_Study_Notes.xlsx, Kidney Tox; Principles & Mechanisms).
40
What is the renal target of NSAID-induced interstitial nephritis? (Domain II)
NSAIDs target renal interstitium, causing immune-mediated inflammation and fibrosis (DABT_Study_Notes.xlsx, Kidney Tox; Web: NIH, 2025).
41
How does cisplatin’s nephrotoxicity involve transporter-mediated uptake? (Domain II)
Cisplatin enters proximal tubule cells via OCT2 and CTR1 transporters, causing ROS and apoptosis (DABT_Study_Notes.xlsx, Kidney Tox; Web: PubMed, 2024).
42
What mechanism does melamine use to cause crystal nephropathy? (Domain II)
Melamine complexes with cyanuric acid, forming insoluble crystals, targeting renal tubules, causing obstruction (DABT_Study_Notes.xlsx, Kidney Tox; Web: FDA, 2024).
43
How does hexachlorobutadiene’s metabolite target the kidney? (Domain II)
Hexachlorobutadiene’s cysteine conjugate is bioactivated by β-lyase, targeting proximal tubule S3, causing DNA damage (DABT_Study_Notes.xlsx, Kidney Tox; Web: PubMed, 2024).
44
What is the renal target of uranium’s chronic toxicity? (Domain II)
Uranium targets glomeruli, causing glomerulosclerosis via chronic oxidative stress (DABT_Study_Notes.xlsx, Kidney Tox; Web: NIH, 2025).
45
How does chloroform cause renal tumors in male mice? (Domain II)
Chloroform’s metabolite phosgene forms DNA adducts, targeting proximal tubules, promoting cell proliferation and tumors (DABT_Study_Notes.xlsx, Kidney Tox; Chemical Carcinogenesis).
46
What mechanism underlies aminoglycoside-induced ototoxicity and nephrotoxicity? (Domain II)
Aminoglycosides disrupt mitochondrial ribosomes, targeting proximal tubules and cochlear hair cells, causing apoptosis (DABT_Study_Notes.xlsx, Kidney Tox; Web: PubMed, 2024).
47
How does lead’s nephrotoxicity differ in children vs. adults? (Domain II)
Children absorb more lead, targeting proximal tubules, causing Fanconi syndrome; adults develop chronic nephropathy (DABT_Study_Notes.xlsx, Kidney Tox; Principles & Mechanisms).
48
What is the renal target of tacrolimus’s acute toxicity? (Domain II)
Tacrolimus targets afferent arterioles, causing vasoconstriction and reduced glomerular filtration rate (DABT_Study_Notes.xlsx, Kidney Tox; Web: PubMed, 2024).
49
How does lithium’s chronic nephrotoxicity manifest? (Domain II)
Lithium causes chronic interstitial nephritis, targeting collecting ducts, via prolonged aquaporin-2 disruption (DABT_Study_Notes.xlsx, Kidney Tox; Web: NIH, 2025).
50
What mechanism does 2,4-D use to cause renal injury? (Domain II)
2,4-D inhibits mitochondrial respiration, targeting proximal tubules, causing oxidative stress and necrosis (DABT_Study_Notes.xlsx, Kidney Tox; Web: EPA, 2024).
51
How does carbon tetrachloride’s nephrotoxicity compare to its hepatotoxicity? (Domain II)
"CCl4 causes proximal tubular necrosis via trichloromethyl radicals, less severe than its CYP2

DABT 2025 (16 decks)

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