Which medications should be stopped or avoided in a patient with acute kidney injury?

Medications to Avoid in Acute Kidney Injury

Immediately discontinue all nephrotoxic medications in patients with AKI, as drugs account for 20-25% of AKI cases and adverse drug events occur in 43% of AKI patients exposed to nephrotoxic or renally eliminated medications. 1, 2

Priority Medications to Stop Immediately

NSAIDs (Highest Priority)

• Stop all NSAIDs immediately - they cause renal vasoconstriction by blocking prostaglandin synthesis, which is critical for maintaining renal blood flow in compromised kidneys 3, 1, 4
• NSAIDs are particularly dangerous when combined with ACE inhibitors/ARBs and diuretics (the "triple whammy"), creating a 53% greater odds of AKI for each additional nephrotoxin 1, 4
• This includes all formulations: ketorolac, ibuprofen, naproxen, diclofenac, meloxicam, and COX-2 inhibitors 4
• NSAIDs should remain discontinued throughout the persistent and recovery phases of AKI 3

ACE Inhibitors and ARBs

• Temporarily hold ACE inhibitors and ARBs during the acute phase when GFR is unstable or volume status is not optimized 5, 1
• These medications decrease glomerular filtration pressure by blocking compensatory mechanisms, potentially worsening kidney function 5
• Do not permanently discontinue - reintroduce after GFR stabilizes and volume status is optimized, as continuing after AKI recovery reduces mortality and cardiovascular events 5
• Restart criteria: GFR stabilized, volume status optimized, mean arterial pressure >65 mmHg, potassium <5.5 mEq/L 5

Aminoglycosides

• Avoid aminoglycosides unless clearly superior in efficacy with no suitable alternative 3, 6
• These cause direct tubular toxicity through cellular dysfunction in proximal tubules 7
• If essential for life-threatening infection, use careful dosing with therapeutic drug monitoring 3

Vancomycin

• Vancomycin is the most common nephrotoxin associated with need for acute kidney support therapy and death in DI-AKI 8
• Only continue vancomycin if the infection is life-threatening and no less nephrotoxic alternative antibiotic is available 1
• Requires intensive therapeutic drug monitoring and volume optimization 1

Additional Nephrotoxic Medications to Avoid

Contrast Media

• Avoid radiocontrast administration during AKI unless absolutely essential 3, 6
• Causes renovasoconstriction and direct tubular injury 3

Amphotericin B

• Avoid unless treating life-threatening fungal infection with no alternative 6, 9
• Causes direct tubular toxicity and electrolyte wasting 9

Chemotherapy Agents

• Hold cytotoxic drugs when possible during AKI 6
• Many cause direct tubular necrosis and crystal nephropathy 7

Acyclovir and Related Antivirals

• Avoid high-dose acyclovir due to crystal precipitation in tubules 3
• Causes crystalline-related AKI through intratubular obstruction 7

Lithium

• Avoid initiating or continuing lithium in AKI 4
• Requires dose adjustment and close monitoring if essential 1

Critical High-Risk Combinations to Never Use

• Never combine NSAIDs + ACE inhibitors/ARBs + diuretics - this "triple therapy" dramatically increases AKI risk through elimination of all renal protective mechanisms 1, 4
• Never combine multiple nephrotoxins simultaneously - each additional nephrotoxin increases AKI odds by 53% 1
• Never combine macrolides with statins - causes rhabdomyolysis through CYP3A4 inhibition 1

Medication Management Algorithm During AKI

Phase 1: Immediate Assessment (Day 1)

• Perform comprehensive medication reconciliation identifying all nephrotoxic and renally eliminated drugs 1
• Discontinue all non-essential nephrotoxins immediately, prioritizing NSAIDs and the triple combination 1
• Hold ACE inhibitors/ARBs if volume status unstable or GFR declining 5, 1

Phase 2: Dose Adjustment (Days 1-3)

• Adjust doses of essential medications based on current eGFR using validated equations 1
• Consider therapeutic drug monitoring for narrow therapeutic window drugs (vancomycin, aminoglycosides) 1
• Recognize that AKI impairs hepatic cytochrome P450 activity, affecting non-renal drug metabolism 1

Phase 3: Intensive Monitoring (Throughout AKI)

• Monitor daily eGFR and serum creatinine 1
• Check electrolytes (especially potassium) daily to twice daily 1
• Obtain therapeutic drug levels for monitored medications 1

Phase 4: Recovery Phase Reassessment

• Systematically reassess which medications can be safely reintroduced 3
• Restart ACE inhibitors/ARBs after GFR stabilization with close monitoring (check renal function and potassium within 1 week) 5
• Continue avoiding NSAIDs until full recovery 3

Safe Analgesic Alternatives During AKI

• Acetaminophen is the preferred first-line analgesic - use up to 3 grams daily with no dose adjustment needed 1, 4
• For severe pain, consider opioids without active metabolites: fentanyl, buprenorphine, or methadone 4
• Avoid morphine and codeine due to accumulation of toxic glucuronide metabolites 4
• Consider topical analgesics (capsaicin, menthol) or intra-articular corticosteroids for localized pain 4

Common Pitfalls to Avoid

• Never use furosemide to "reverse" established AKI - this leads to inappropriate fluid overload without benefit 1
• Never fail to document medication restart plans - 66% of adverse drug events in AKI are preventable, with failure to adjust for kidney function being the most common error (63%) 2
• Never delay essential antibiotics for infection - treatment of life-threatening infections should begin immediately as this may actually prevent or ameliorate AKI 1
• Never assume serum creatinine alone reflects GFR - use calculated eGFR for decision-making as creatinine can remain normal despite significantly reduced GFR 4

Patient Education for AKI Recovery

• Educate patients to avoid NSAIDs and new medications without consulting their physician 1
• Teach "sick-day rules" for temporary discontinuation of ACE inhibitors/ARBs during acute illnesses that increase AKI risk 4
• Ensure coordination with nephrology team for any medication changes 4