What are examples of nephrotoxic (kidney damaging) drugs?

Nephrotoxic Drugs: Major Categories and Clinical Management

Avoid NSAIDs, aminoglycosides, contrast media, calcineurin inhibitors, and amphotericin B whenever safer alternatives exist, as these represent the most common causes of drug-induced kidney injury in clinical practice. 1, 2

High-Risk Nephrotoxic Drug Classes

NSAIDs and COX-2 Inhibitors

• NSAIDs are particularly harmful in patients with pre-existing kidney insufficiency or diminished kidney blood flow and should be avoided. 1, 2
• These agents cause renovasoconstriction and can precipitate acute kidney injury, especially when combined with ACE inhibitors/ARBs and diuretics (the "triple whammy"). 1
• Use acetaminophen as the preferred analgesic for non-inflammatory pain in patients with kidney dysfunction. 1, 2
• Consider low-dose opiates (monitoring for constipation) or short courses of corticosteroids for inflammatory conditions. 1

Aminoglycoside Antibiotics

• Gentamicin and other aminoglycosides cause direct tubular toxicity and are potentially nephrotoxic, with risk increasing in patients with impaired renal function and those receiving high doses or prolonged therapy. 3
• Each nephrotoxin administration increases odds of developing AKI by 53%, and this risk compounds when multiple nephrotoxins are combined. 1
• Monitor peak levels to avoid prolonged concentrations above 12 mcg/mL and trough levels above 2 mcg/mL. 3
• In peritoneal dialysis patients, retrospective data show aminoglycosides are associated with faster decline in residual kidney function, though evidence is somewhat contradictory. 1
• Use less nephrotoxic antibiotics whenever possible without compromising antibacterial efficacy. 1

Contrast Media

• Intravenous or intra-arterial contrast dye is nephrotoxic, especially in patients with pre-existing kidney dysfunction, particularly diabetic nephropathy. 1, 2
• Before administering contrast, review the indication carefully and seek alternative non-contrast studies. 1
• For essential studies, ensure adequate hydration, use the smallest volume of the least nephrotoxic agent, and avoid volume depletion. 1, 2
• Consider pre-treatment with N-acetylcysteine given its low cost and favorable side-effect profile, though evidence for efficacy is controversial. 1

Calcineurin Inhibitors

• Cyclosporine and tacrolimus cause nephrotoxicity through multiple mechanisms. 2, 4
• These immunosuppressants require careful monitoring in transplant and autoimmune disease patients. 4

Antifungal Agents

• Amphotericin B is a well-established nephrotoxic agent requiring close monitoring. 4, 5

Drug Interaction Risks

Dangerous Combinations

• The "triple whammy" of NSAIDs + diuretics + ACE inhibitors/ARBs more than doubles AKI risk. 1
• Escalating from two to three nephrotoxic medications more than doubles AKI risk, with 25% of non-critically ill patients developing AKI when receiving three or more nephrotoxins. 1
• Macrolide antibiotics (clarithromycin, erythromycin) combined with statins increase AKI risk from rhabdomyolysis due to impaired statin clearance via CYP3A4 inhibition. 1
• Avoid concurrent use of aminoglycosides with other nephrotoxic agents including cisplatin, vancomycin, polymyxin B, and potent diuretics like furosemide or ethacrynic acid. 3

Additional Nephrotoxic Mechanisms

Crystal-Induced Nephropathy

• Acyclovir can cause tubular obstruction through crystallization. 1, 2

Interstitial Nephritis

• β-lactam antibiotics and NSAIDs can trigger acute interstitial nephritis through type IV hypersensitivity reactions. 1, 6

Other Chemotherapeutic Agents

• Cisplatin causes direct tubular toxicity and requires careful monitoring. 3, 5

Risk Factors for Drug-Induced Nephrotoxicity

• Pre-existing chronic kidney disease significantly increases vulnerability to nephrotoxic drugs. 1
• Diabetes mellitus heightens risk of drug-induced nephrotoxicity. 2
• Advanced age and dehydration increase toxicity risk. 3
• Hypercalcemia can amplify nephrotoxic effects. 2
• Previous history of AKI or patients already taking multiple nephrotoxic medications are at elevated risk. 1

Prevention and Monitoring Strategies

Core Principles

• Administer potentially nephrotoxic medications only when necessary and for the shortest duration possible. 2
• Monitor kidney function closely in all patients exposed to nephrotoxic agents. 2
• Ensure adequate hydration, particularly when administering contrast media or other high-risk agents. 1, 2

Specific Monitoring

• Check BUN, serum creatinine, and creatinine clearance periodically during treatment. 3
• Examine urine for decreased specific gravity, increased protein excretion, and presence of cells or casts. 3
• Obtain serial audiograms when feasible for aminoglycoside therapy, especially in high-risk patients. 3

Clinical Pitfalls

• Drug-associated nephrotoxicity accounts for 20-27% of acute kidney injury cases in hospitalized patients and up to 60% in some series. 7, 4, 6
• Serum drug levels frequently fail to correlate with degree of nephrotoxicity in individual patients. 5
• Renal and eighth cranial nerve dysfunction from aminoglycosides may not manifest until after therapy completion. 3
• Early signs of injury can be subtle (minor electrolyte changes) or dramatic (acute renal failure), making vigilance essential. 5

During Acute Kidney Disease

• Continue nephrotoxin avoidance throughout the persistent phase of AKD. 1
• Exercise caution when initiating nephrotoxins during the recovery phase to prevent re-injury. 1
• Educate patients to avoid NSAIDs and consult before taking new medications, and use ACE inhibitors, decongestants, antivirals, antibiotics, and herbal products with caution. 1