21 - Nephrotoxicity

Question 1

Diagnostic criteria of acute kidney injury

Answer 1

• Abrupt decline in GFR
• • sCr by 0.3 mg/dL or more w/in 48 h, OR
• • sCr to 1.5 times or more baseline w/in 7 days, OR
• • Urine volume < 0.5 mL/kg/h for 6 hours

Question 2

Pre-renal AKI means ____

Answer 2

Impaired renal perfusion

Question 3

Causes of pre-renal AKI

Answer 3

• Volume depletion (diuretics, cathartics, emetics)
• Bleeding (anticoagulants)
• Cardiac dysfunction (beta-blockers, cardiotoxins)
• Vasoconstriction (NSAIDs, calcineurin inhibitors, ex: cyclosporine)

Question 4

Renal AKI means ____

Answer 4

Intrinsic damage

Question 5

Causes of renal AKI

Answer 5

• Vascular -> cyclosporine, tacrolimus, quinine, clopidogrel
• Glomerular (ACE inhibitors, NSAIDs)
• Acute tubular necrosis (acetaminophen, aminoglycosides, antifungals, chemotherapeutic agents, iodinated contrast media)
• Acute interstitial nephritis (hypersensitivity) -> antimicrobials, NSAIDs, diuretics, antihistamines, PPI

Question 6

What is the most common cause of AKI?

Answer 6

Pre-renal

Question 7

Post-renal AKI means ____

Answer 7

Obstruction of urine flow

Question 8

Causes of post-renal AKI

Answer 8

• Bladder dysfunction (anticholinergics, antipsychotics)
• Crystal forming (acyclovir, ciprofloxacin, methotrexate, sulfonamides)
• Retro-peritoneal fibrosis (beta-blockers, bromocriptine, hydralazine, methyldopa)

Question 9

Risk factors for chronic kidney disease

Answer 9

• Pre-existing renal impairment
• Dehydration (diuresis, vomiting or diarrhea, hemorrhage)
• Medical conditions (cirrhosis, HF, DM)
• Multiple nephrotoxic agents
• Seriously ill (septic shock, hypotension)
• Advanced age

Question 10

Which NSAIDs are most nephrotoxic?

Answer 10

All equally nephrotoxic

Question 11

Mechanism of NSAID nephrotoxicity

Answer 11

• Pre-renal (decreases vasodilatory prostaglandins => vasoconstriction => decreased renal blood flow)
• Acute interstitial nephritis

Question 12

Clinical manifestations of NSAID nephrotoxicity

Answer 12

• Increased plasma creatinine
• Decreased renal blood flow and GFR
• Oliguria

Question 13

Prevention of NSAID nephrotoxicity

Answer 13

• Avoid NSAIDs among high-risk px
• Monitor creatinine levels closely
• Avoid NSAIDs prior to procedures involving radiocontrast

Question 14

Mechanism of aminoglycoside nephrotoxicity

Answer 14

• Proximal tubular necrosis

- Interstitial nephritis

Question 15

Clinical manifestations of aminoglycoside nephrotoxicity

Answer 15

• Increased plasma creatinine
• Increased BUN
• Non-oliguric
• Electrolyte abnormalities (infrequent)

Question 16

Aminoglycoside-related risk factors for nephrotoxicity

Answer 16

• Elevated serum drug concentrations
• Prolonged duration of therapy
• Type of aminoglycoside (gentamicin > tobramycin > amikacin)
• • B/c gentamicin has highest affinity
• Frequency of dosing (once daily vs. traditional dosing)

Question 17

Prevention of aminoglycoside nephrotoxicity

Answer 17

• Avoid in px w/ risk factors
• Adjust dose for renal function
• Correct hypokalemia and hypomagnesemia
• Limit duration of therapy to 7-10 days
• Minimize concomitant nephrotoxic medications
• Choose aminoglycoside w/ less nephrotoxicity
• Monitor aminoglycoside serum concentration
• Utilize a once-daily dosing regimen

Question 18

Mechanism of iodinated contrast media nephrotoxicity

Answer 18

High osmolality => acute tubular necrosis and vasoconstriction

Question 19

What are properties of the newest iodinated contrast media?

Answer 19

• Non-ionic dimers

- Iso-osmolal

Question 20

Clinical manifestations of iodinated contrast media nephrotoxicity

Answer 20

• Within 24-48 h after exposure
• Mild increase in sCr
• Usually non-oliguric
• Hyperkalemia, acidosis, hyperphosphatemia

Question 21

Dye-related risk factors for iodinated contrast media nephrotoxicity

Answer 21

• Dose of contrast agent
• Type of contrast agent
• Specific procedure (intra-arterial vs. IV and interventional vs. diagnostic angiography)

Question 22

Pt-related risk factors for iodinated contrast media nephrotoxicity

Answer 22

• GFR < 60 mL/min + significant proteinuria (proteinuria > 500 mg/day)
• GFR < 60 mL/min + comorbidities (DM, HF, liver failure, or multiple myeloma)
• GFR < 45 mL/min
• GFR < 30 mL/min (highest risk)

Question 23

Prevention of iodinated contrast media nephrotoxicity

Answer 23

• Avoid volume depletion
• Withhold NSAIDs for 24-48 h prior to procedure
• Dose and type of contrast agent:
• • Use lowest effective dose
• • Avoid high osmolality agents, use iso-osmolal agent or nonionic low-osmolal agents (2nd or 3rd gen agents)
• For at-risk px/risky procedures -> hydrate w/ IV isotonic saline