What medications should be avoided or used with caution in patients at risk of acute kidney injury?

Medications to Avoid in Acute Kidney Injury

Immediately discontinue NSAIDs, ACE inhibitors/ARBs, and diuretics (the "triple whammy" combination) in patients with acute kidney injury, as this combination dramatically increases the risk of further renal damage and delays recovery. 1, 2

Primary Nephrotoxic Medications Requiring Immediate Cessation

RAAS Blockers (ACE Inhibitors and ARBs)

• Temporarily discontinue all ACE inhibitors and ARBs until GFR stabilizes and volume status is optimized. 1, 2, 3
• These agents cause functional AKI through elimination of angiotensin II-mediated efferent arteriolar vasoconstriction, particularly dangerous in hypovolemic states. 1
• Do not restart until kidney function has stabilized and the patient is euvolemic. 1
• Two studies demonstrated increased 30-day mortality when these agents were not restarted post-operatively, likely from hypertensive rebound causing cardiac decompensation, so plan for careful reintroduction after recovery. 1

NSAIDs (All Formulations)

• Stop all NSAIDs immediately, including over-the-counter formulations, as they reduce renal perfusion through prostaglandin inhibition. 1, 2, 3
• NSAIDs should be avoided in elderly patients with creatinine clearance <30 ml/min per the Beers criteria. 1
• The combination of NSAIDs with ACE inhibitors/ARBs and diuretics creates the "triple whammy" that exponentially increases AKI risk. 2, 3
• Use acetaminophen (up to 3 grams daily) as the preferred alternative analgesic. 4

Diuretics

• Temporarily withhold diuretics unless absolutely necessary for volume overload, as they can worsen renal perfusion and exacerbate AKI. 2, 5
• Loop diuretics were associated with the highest risk of AKI (HR 1.64) in hospitalized patients. 5
• Potent diuretics like furosemide and ethacrynic acid can cause ototoxicity and enhance aminoglycoside toxicity. 6

Antibiotics and Antimicrobials Requiring Dose Adjustment or Avoidance

Aminoglycosides (Gentamicin, Tobramycin, Amikacin)

• Avoid aminoglycosides entirely if less nephrotoxic alternatives exist; if essential, monitor peak levels (<12 mcg/mL) and trough levels (<2 mcg/mL) closely. 6
• The FDA mandates close monitoring of renal function and eighth cranial nerve function, with urine examination for decreased specific gravity, proteinuria, and cellular casts. 6
• Risk increases with advanced age, dehydration, pre-existing renal impairment, and concurrent use of other nephrotoxins. 6, 7
• Avoid concurrent use with vancomycin, cisplatin, or other nephrotoxic agents. 6

Trimethoprim-Sulfamethoxazole

• Avoid if creatinine clearance is <15 ml/min. 1, 2
• Associated with increased AKI risk in both hospitalized and discharged patients. 8

Vancomycin

• Use only when no less nephrotoxic alternatives exist for life-threatening infections; requires therapeutic drug monitoring. 3
• Avoid combination with aminoglycosides due to synergistic nephrotoxicity. 6

Antidiabetic Medications

Metformin

• Discontinue metformin if GFR <30 ml/min/1.73m² and review carefully if GFR 30-44 ml/min/1.73m². 2
• Risk of lactic acidosis increases substantially with declining renal function. 2

Cardiovascular Medications

Digoxin

• Temporarily cease digoxin due to risk of toxicity with reduced renal clearance; monitor drug levels closely. 2

Spironolactone

• Use with extreme caution or avoid, as it had risk estimates ≥3 for AKI across multiple study methodologies. 8

Antiviral Medications

Tenofovir

• Avoid tenofovir with concurrent or recent use of nephrotoxic agents (particularly high-dose or multiple NSAIDs). 9
• Can cause acute renal failure and Fanconi syndrome. 9
• Requires monitoring of bone mineral density due to associated decreases. 9

Contrast Media and Imaging Agents

Iodinated Radiocontrast

• Avoid when possible; if essential, use the lowest possible dose with adequate pre- and post-hydration. 2

Gadolinium-Based Contrast

• Do not use in patients with GFR <15 ml/min/1.73m². 2

Additional High-Risk Medications

Lithium

• Discontinue and monitor drug levels closely. 2

Calcineurin Inhibitors (Tacrolimus, Cyclosporine)

• Require drug level monitoring and possible dose adjustment rather than complete discontinuation. 2

Proton Pump Inhibitors

• Consider discontinuation if non-essential, as they are associated with acute interstitial nephritis. 8, 10

Critical Drug Combinations to Avoid

• Never combine NSAIDs + ACE inhibitors/ARBs + diuretics ("triple whammy"). 2, 3
• Avoid macrolide antibiotics (clarithromycin) with statins, as CYP3A4 inhibition increases statin levels and rhabdomyolysis risk. 1
• Each additional nephrotoxic medication increases AKI odds by 53%; escalating from two to three nephrotoxins more than doubles AKI risk. 3

Monitoring and Management Principles

When to Avoid Starting a Nephrotoxin

• Patient has known AKI risk factors (advanced age, previous AKI, CKD, diabetes, proteinuria, hypertension). 1
• A less nephrotoxic alternative is available. 1
• The nephrotoxin is non-essential. 1
• Patient is already receiving another nephrotoxic drug. 1
• Concern exists for lack of appropriate follow-up monitoring. 1

When to Discontinue a Nephrotoxin

• Causal relationship evaluation indicates the nephrotoxin is the potential cause of AKI. 1
• A less nephrotoxic alternative is available. 1
• The nephrotoxin is non-essential. 1

General Management Approach

• Identify all potentially nephrotoxic medications in the patient's regimen and assess necessity of each. 2
• Minimize duration and dose of nephrotoxin exposure when use is unavoidable. 1, 3
• Follow evidence-based dosing guidelines with regular monitoring of renal function. 1
• Resume medications cautiously after kidney function improves, with close monitoring. 2

Common Pitfalls to Avoid

• Do not extrapolate CKD dosing guidelines to AKI patients, as the time course and organ crosstalk effects differ significantly. 1
• Do not overlook over-the-counter medications and herbal remedies, which may contain nephrotoxic compounds. 1, 2
• Do not restart ACE inhibitors/ARBs too early; wait until GFR stabilizes and volume status is optimized to avoid functional AKI recurrence. 1
• Do not assume antibiotics are safe in AKI; they were independently associated with increased AKI risk (HR 1.13 in hospitalized patients, HR 3.19 in discharged patients). 5