Nephrotoxins (done)

Question 1

Categories of drug induced kidney disease (or ways in which drugs cause kidney diease)

Answer 1

1. AKI (pre/intrinsic/post)
2. nephrolithiasis
3. HTN
4. proteinuric
5. tubulopathies
6. CKD

Question 2

See image for case

Question: Which of the following is a direct effect of NSAID?
AKI
hyperK
HypoNa
worsening HTN
Hypervolemia
All of the above

Answer 2

All of the above - see image

Question 3

Other drugs that cause hemodynamic/ishemic AKI

Answer 3

Question 4

Other renal diseases/pathologies 2/2 NSAIDS

Answer 4

Question 5

Other drug induced renal pathologies/GNs/etc

Answer 5

Question 6

Case 2 (see image)
What is the most likely cause of AKI?
- acute GN
- AIN
- ATN/AKI
- acute urate nephropathy
- acute cast nephropathy

Answer 6

ATN: seen biopsy; noted: tubular drop out, dilation

Question 7

Other drugs that cause ATN

Answer 7

Question 8

Tenofovir AKI mechanisms

Answer 8

ATN
is filtered and secreted (more PCT secretion when GFR down)
- in from basolateral via OAT
- can have disruption in transported to apical/urine side OATs, drug can accumulate in tubular cell, cause mitochondria tox/injury

*fanconi/nephrogenic DI/proteinuria

Question 9

Pathology of tenofovir

Answer 9

large red blobs are swollen mitochondrial injury

Question 10

Know for the boards/summary Tenofovir AKI

Answer 10

Question 11

Aminoglycoside ATN mechanism

Answer 11

ATN
filtered, apical membrance attracts AG
- brought in, fuse with lysosome to traffic
- injury mitochondria
- cause myeloid body formation (spiral)

7-10 days in 10-30% patients
- nonoliguric, electrolyte disturbances
- recovers, but takes time

Question 12

Aminoglycoside biopsy/pathology

Answer 12

myeloid/myelin body

Question 13

Aminoglycoside tubulopathy - wastes what electrolytes? similar to what syndrome

Answer 13

Ur wasting: Ca/Mg/Cl/K, met alkalosis
- interferes with CaSR, competes with Ca, inhibits NKCC, ROMK
- Bartter like

*also could be fanconi - in NHE, met acid, Na/K wasting

Question 14

Aminoglycosides summary for the boards

Answer 14

Question 15

Polymixin/Colistin AKI mechanism

Answer 15

- freely filtered, in urine
- move via transporters and once inside, destroy apical membrane
- membranolytic
- Na/Cl everything moves into the cell and causes injury

Question 16

Polymixin/Colistin for the boards/summary

Answer 16

Question 17

Vancomycin mechanism of AKI

Answer 17

ATN
- dose related (15-20 trough)
- filtered and secreted
- inc ROS -> Comp activation -> mitochondrial injury

**also couples with Uromodulin can cause a cast nephropathy

Question 18

Vancomycin for the boards/summary

Answer 18

Question 19

Amphotericin B mechanism of AKI

Answer 19

AKI/ATN
- renal vasoconstriction
- creates pores, inc permeability (leak Mg/K/H+ out of cell)
- tubular injury

Question 20

What type of RTA is associated with AmphoB?

Answer 20

Type IV RTA (distal)

Question 21

Drugs that cause AKI/ATN

Answer 21

Question 22

Case 3 question

What’s the lesion on biopsy:
- AKI/ATN
- AIN
- acute tubular lipidosis
- acute crystalline nephropathy
- acute osmotic nephropathy

Answer 22

Answer: acute osmotic nephropathy

Question: what is the cause?
- vanco
- gent
- hydroxyethyl starch
- LR
- high dose furosemide

Question 23

Mechanism of osmotic AKI

Answer 23

• pincytosis of osmotic agent
• lysosomal trafficing
• cellular swelling and injury within tubular cell

Question 24

Osmotic Nephropathy causes for the boards/summary

Answer 24

Question 25

Case 4: What is the cause of AKI? - tenofovir - emtricitabine - ritonavir - atazanavir - ascorbic acid

Answer 25

Atazanavir crystalline nephropathy

Question 26

Drugs that cause crystalline nephropathy

Answer 26

cipro crystals in top picture - needle like into starburst pattern/shape biopsy: crystalline casts in tubules from indinavir

Question 27

Atazanavir crystal images

Answer 27

Question 28

Ciprofloxacin causes crystallization in what type of urine pH?

Answer 28

Alkaline makes it more soluble

Question 29

Cipro on pathology

Question 30

Other AKIs from Quinolones/ciprofloxacin

Answer 30

most common: AIN/granulomatous toxic ATN crystalline AKI nec. vasculitis

Question 31

Methotrexate induced AKI

Answer 31

- associated with high doses - dec ADA activity - MTX/7-OH MTX (metoabolite) crystals in DCT - RF: volume depelation/acidic urine/underlying AKI/CKD

Question 32

MTX Crystal images

Answer 32

Question 33

Treatment of MTX

Answer 33

1. Leucovorin 2. High flus HD 3. Glucarbidase - cleaves to non-toxic metabolite

Question 34

Crystalline AKI to know for the boards

Answer 34