Nephrotoxins

Question 1

Are NSAIDs associated with renal cancer?

Answer 1

Yes

Question 2

Drugs causing TMA

Answer 2

Gemcitabine, Mitomycin C, VEGF inhibitors, Ticlopidine, Clopidogrel, Calcineurin inhibitors, Oxymorphone IR, Quinine

Question 3

Drugs causing ANCA vasculitis

Answer 3

Levamisole( antihelminth), Propylthiouracil, Infliximab, Hydralazine, Allopurinol

Question 4

Interferon injections and kidney disease: mechanism of injury and lesions

Answer 4

Mechanism of injury: podocyte injury and TMA

Lesions: Minimal change disease, FSGS NOS, Collapsing FSGS

Question 5

How does Tenofovir cause proximal tubular injury?

Answer 5

Not by filtered portion, but some get secreted from basolateral membrane via OAT. If there is defect in efflux pump like MRP2, accumulation and mitochondrial damage

Question 6

Mechanism of Aminoglycoside induced tubular damage?

Answer 6

1) AG(++ charged)> filtration( not secretion)> absorped via megalin and cubulin pathways on proximal tubules> damages lysosomes and mitochondria
2) Bartter like syndrome: on TAL> basolateral side> activate Ca sensing receptor> inhibits NKCC> decrease ROMK> loss of Na, K, calciuria
- on EM damaged lysosomes/ mitochondria: Myeloid bodies( lamellate kind of)

Question 7

Mechanism of tubular damage by Polymixin and Colistin?

Answer 7

They are cationic polypeptide> filtered> taken inside proximal tubules via some pump> once they are inside, they punch holes on luminal side> hence damage

Question 8

Mechanism of tubular damage by Amphotericin?

Answer 8

• renal vasoconstriction and it punches hole on tubular cells> leak of K, Mg and back leak of H+; distal renal tubular acidosis > Nephrogenic DI
• Prevention: salt loading

Question 9

Causes of osmotic nephropathy?

Answer 9

Drug deposition in tubular lysosomes, cells look swollen foamy like to me
Hydroxyethyl starch, IVIG sucrose, Dextran 40(historic), Mannitol, Radiocontrast agents

Question 10

Drugs causing crystalline nephropathy?

Answer 10

• Atazanavir/ Indinavir, Ciprofloxacin, Acyclovir, Sulfonamides, Methotrexate high dose, Ascorbic acid, Orlistat, Triamterene
• Note Ciprofloxacin can cause crystalline nephropathy and AKI, insoluble in alkaline ph other than AIN/ granulomatous AIN

Question 11

Principles of drug dosing in kidney disease

Answer 11

• reduce the dose, keep the interval ( anticonvulsants, antiarrhythmics)
• keep the same dose, increase the interval ( antibiotics)

Question 12

Gentamicin and electrolyte abnormalities

Answer 12

-K , Mg and Calcium loss

Question 13

Which chemical might be in weight loss regimen?

Answer 13

Aristolochic acid ( chinese herb)> rapidly progressive AIN and ESRD