What medications are safe or unsafe to use in patients with Acute Kidney Injury (AKI)?

Medications Safe and Unsafe in Acute Kidney Injury

Medications That Must Be Discontinued Immediately

The following nephrotoxic medications should be stopped immediately when AKI develops to prevent further kidney damage and promote recovery:

High-Priority Discontinuations

• NSAIDs must be stopped immediately as they reduce renal perfusion through prostaglandin inhibition and are among the most common causes of drug-induced AKI 1, 2
• ACE inhibitors and ARBs should be temporarily discontinued in AKI, particularly in the setting of acute hypovolemia, as they cause functional AKI and are associated with a 50% increase in AKI-related hospitalizations 3, 1
• The "triple whammy" combination (NSAIDs + diuretics + ACE inhibitors/ARBs) dramatically increases AKI risk and represents one of the most dangerous medication combinations 1, 4

Additional Medications Requiring Immediate Review

• Metformin must be discontinued if GFR <30 ml/min/1.73m² and reviewed if GFR is 30-44 ml/min/1.73m² due to lactic acidosis risk 1
• Lithium requires discontinuation with close monitoring of drug levels due to reduced renal clearance 1
• Digoxin should be temporarily ceased because of toxicity risk with reduced renal clearance 1
• Iodinated radiocontrast media should be avoided when possible, and if essential, use the lowest dose with adequate hydration 1
• Gadolinium-based contrast agents should not be used if GFR <15 ml/min/1.73m² 1

Antibiotics and Antimicrobials: Risk Stratification

High Nephrotoxic Risk - Use With Extreme Caution

• Aminoglycosides (especially gentamicin) have the highest reporting odds ratio (>10) for AKI and cause direct acute tubular necrosis through cellular toxicity 5, 2
• Vancomycin is the primary nephrotoxin in hospitalized patients and is associated with higher need for acute kidney support therapy and death 6, 7
• Amphotericin B causes significant tubular injury but paradoxically shows lower risk of requiring dialysis or death in some cohorts 6
• Acyclovir has a reporting odds ratio >10 and causes crystalline nephropathy through intratubular precipitation 2
• Trimethoprim-sulfamethoxazole should not be used if creatinine clearance <15 ml/min 3, 1

Moderate Risk - Requires Dose Adjustment

• Cisplatin and other antineoplastic agents have reporting odds ratios >10 and require dose adjustment rather than complete discontinuation in cancer patients 1, 2
• Tenofovir can cause new or worse kidney problems including kidney failure and requires blood tests to monitor kidney function before and during treatment 8
• Calcineurin inhibitors require drug level monitoring and possible dose adjustment 1

Lower Risk - Generally Safe With Monitoring

• Nitrofurantoin, TMP-SMX, and fosfomycin are first-line UTI agents but require dose adjustment in AKI 4
• Beta-lactam antibiotics can cause acute interstitial nephritis but are generally safer than aminoglycosides 3, 9

Critical Drug Interactions That Increase AKI Risk

• Escalating from two to three nephrotoxic medications more than doubles AKI risk 1
• Certain macrolide antibiotics combined with statins increase rhabdomyolysis-induced AKI risk through CYP3A4 inhibition 3
• Opioids are associated with higher hazard of AKI in ICU patients after adjustment for confounding 5
• Sympathomimetics with α- and β-effects show controversial associations with AKI 5

Medications Generally Safe in AKI (With Appropriate Dosing)

While the evidence focuses primarily on nephrotoxic agents, the following principles apply:

• Medications with primarily hepatic metabolism and non-renal excretion are safer alternatives when available 3
• Antibiotics should be selected based on local antibiogram patterns with appropriate renal dose adjustment 4
• Broad-spectrum antibiotics should be started when infection is strongly suspected despite AKI, as treating infection may prevent further kidney injury 3

Management Algorithm for Medication Review in AKI

Phase 1: Immediate Assessment (Within Hours of AKI Recognition)

1. Identify and discontinue all nephrotoxic medications immediately, particularly NSAIDs, ACE inhibitors/ARBs, and the "triple whammy" combination 3, 1
2. Review all over-the-counter medications and herbal remedies as they may contain nephrotoxic compounds 1
3. Assess for multiple concomitant nephrotoxins (present in 66% of drug-induced AKI cases) 2

Phase 2: Ongoing Management (During AKI Persistence)

• Drug selection should be guided by the functional phase, trajectory, and stage of AKI with personalized clinical decision-making 3
• Consider renal versus non-renal excretion pathways, potential for nephrotoxicity, effect on metabolites, urgency of use, and availability of alternatives 3
• When nephrotoxic medications are clinically essential, efforts should be made to mitigate effects and avoid multiple nephrotoxins concomitantly 3

Phase 3: Recovery Phase

• Resume medications cautiously after kidney function improves with close monitoring of renal function 1
• Educate patients to avoid NSAIDs or new medications without consulting their physician, and to use ACE inhibitors, decongestants, antivirals, antibiotics, and herbal products with caution 3
• Continued caution is warranted during recovery to prevent re-injury 3

Common Pitfalls to Avoid

• Do not assume a single creatinine threshold applies to all nephrotoxins - each drug class has specific recommendations 3
• Do not treat asymptomatic bacteriuria in AKI patients as this unnecessarily exposes them to nephrotoxic antibiotics 4
• Do not delay essential antibiotics for life-threatening infections - treating sepsis may actually prevent or ameliorate AKI 3
• Do not forget that drug-induced AKI shows lower mortality than other AKI etiologies (25.2% vs 35.4%) but similar need for dialysis, making early recognition and intervention crucial 6