Drug-Induced Kidney Disease

Question 1

What drugs cause HEMODYNAMICALLY MEDIATED renal injury? (5)

Answer 1

ACEis
ARBS
NSAIDS
SGLT2is
Calcineurin inhibitors

Question 2

What drugs cause PRE-RENAL kidney injury? (1)

Answer 2

Diuretics (loop > thiazide)

Question 3

What drugs cause POST-RENAL injury/NEPHROLITHIASIS? (5)

Answer 3

Furosemide
Acyclovir
Topiramate
Allopurinol
Sulfonamides
(FAT AS)

Question 4

What are RISK FACTORS for drug-induced renal disease? (7)

Answer 4

Concomitant nephrotoxins
Renin-dependent state (low circulating volume - HF, cirrhosis)
Elderly (>65)
Duration

CKD
Known allergy to drug
DM/HTN
(CRED CKD [credit CKD for risk of injury!])

Question 5

What are the KEYS to preventing drug-induced kidney injury?

Answer 5

**Avoid nephrotoxic meds in high risk patients!
Maintain kidney perfusion (hydration)
TDM/Proactive monitoring

Question 6

What fluid type should be used for maintaining perfusion in drug induced kidney injury patients?

Answer 6

Balanced crystalloids (Lactated ringers, Plasma-Lyte)

Question 7

What are the mechanisms of SGLT2is, NSAIDs and ACEi/ARBs in causing hemodynamic renal damage?

Answer 7

NSAIDS - block dilation of afferent (input) arteriole
SGLT2is - stimulates constriction of afferent (input) arteriole
ACEi/ARBs - block constriction of efferent (output) arteriole

Question 8

SGLT2is increase ______ which causes the afferent arteriole to ________ (constrict/dilate), decreasing GFR.

Answer 8

Increase Na+
Causes constriction

Question 9

How do we treat pre-renal/hemodynamically mediated renal injury?

Answer 9

D/C offending agent
Maintain sufficient circulating volume with fluids (NS)
Monitor SCr/BUN and electrolytes

Question 10

What types of intrinsic renal injury are there? (3)

Answer 10

Acute Tubular Necrosis (ATN)
Acute interstitial nephritis (AIN)
Glomerulonephritis (GN)

Question 11

What are the main three causative agents of ATN? What are three other general causes?

Answer 11

*Aminoglycoside
*Amphotericin B
*IV Contrast media
(ATN to your ABCs)

Antineoplastic agents
Direct Cellular toxicity
Prolonged ischemia

Question 12

What is the clinical presentation of ATN?

Answer 12

Deteriorating renal function (increasing SCr and BUN, decreasing GFR and urine output)
Urinalysis = proteinuria, cellular debris, muddy brown color, granular casts

Metabolic acidosis
Hyperkalemia
FeNa > 1%
Magnesium wasting

Question 13

Nephrotoxicity with aminoglycoside is linked to _______ ____________. TDM and individualized dosing should be used.

Answer 13

Trough concentrations

Question 14

What are the goal troughs of gentamicin/tobramycin and amikacin?

Answer 14

Gentamicin/tobramycin ≤2mg/L
Amikacin ≤8 mg/L
(Extended interval dosing may reduce risk of nephrotoxicity)

Question 15

A single concentration at ____ to ____ hours can be used for TDM for aminoglycosides

Answer 15

6-18 hours

Question 16

What are the management strategies for ATN? (5)

Answer 16

Supportive care
D/C offending agent and other nephrotoxic drugs
Maintain hydration & euvolemia
Electrolyte management
Kidney replacement therapy if SEVERE ATN (hemodialysis)

Question 17

What are risk factors for CIN (contrast induced nephritis)? (8)

Answer 17

DIABETES**
LARGE DOSE (volume) IODINATED CONTRAST**
IONIC CONTRAST**
SHORT TIME INTERVAL between 2 admins**
HIGH OSMOLAL CONTRAST**

[CKD (GF<60 ml/min/1.73m2)]
[Concomitant nephrotoxic agents]
[Low effective circulatory volume]

D’LISH

Question 18

What’s are 3 drugs/fluids that prevent CIN? Which one is possibly harmful?

Answer 18

Saline hydration** - gold standard
NAC - conflicting evidence, possible benefits
Sodium bicarbonate - conflicting, POSSIBLE HARM! Avoid!!

Question 19

What 8 drugs cause AIN (acute interstitial nephritis)

Answer 19

Vancomycin
Beta-lactams

PPIs
Anti-epileptics
NSAIDs
Diuretics
Allopurinol
Sulfa drugs

Very Big PANDAS

Question 20

What treatments are there for drug-induced AIN?

Answer 20

Stop offending drug/avoid DDI drugs
Supportive care
**Steroids (early, aggressive therapy may improve long term renal outcomes)

Question 21

What are some risk factors for vancomycin-associated AKI? (6)

Answer 21

Elevated trough concentrations
AUC > 600
Daily dose > 4 g
Duration > 7 days
Severe illness
Weight > 101.4 kg

Question 22

What are the 3 main ways to prevent vancomycin-associated AKI?

Answer 22

Stewardship - don’t overuse vanco!
Avoid concomitant drugs - aminoglycosides, amphoterecin, contrast (same as ATN drugs)
Monitoring - Frequent monitoring in high-risk patients

Question 23

What are the top 3 causative agents of drug-induced nephrolithiasis? (There are 6 others as well)

Answer 23

**Topiramate
**Sulfonamides
**Furosemide
Allopurinol
Acyclovir
Calcium
Foscarnet
Indinavir
Zonisamide

Question 24

What is the treatment for drug-induced nephrolithiasis?

Answer 24

Hydration (to induce diuresis)
Pain management
Lithotripsy - using shockwaves to disintegrate kidney stones

Question 25

What is rhabdomyolysis and what drugs induce it?

Answer 25

Mechanism = intratubular precipitation of myoglobulin from muscle breakdown Drugs that cause it = statins and statin+vibrate combos

Question 26

What is the treatment/management of rhabdomyolysis?

Answer 26

D/C agent (statin) Aggressive IV fluids +/- urinary alkalization

Question 27

Lithium may induce CKD from cumulative lithium exposure. What drug may help manage the polydipsia and polyuria?

Answer 27

Amiloride 5-20 mg QD

Question 28

What is the Cockcroft-Gault equation

Answer 28

(140-age) x IBW / (72 x SCr) IBW (M) = 50 + (2.3 x height over 5’) IBW (F) = 45.5 + (2.3 x height over 5’)

Question 29

What drug has a major interaction with lithium that may contribute to inducing CKD?

Answer 29

Hydrochlorothiazide