What are examples of nephrotoxic substances?

Comprehensive List of Nephrotoxic Substances

The most important nephrotoxic substances to be aware of include aminoglycosides, NSAIDs, contrast media, amphotericin B, and ACE inhibitors/ARBs in specific clinical scenarios. These substances can cause acute kidney injury through various mechanisms and should be used with caution, especially in patients with pre-existing kidney disease.

Categories of Nephrotoxic Substances

Antimicrobials

• Aminoglycosides (e.g., gentamicin, streptomycin) 1, 2

  • Cause direct tubular toxicity
  • Risk increases with prolonged therapy and higher doses
  • Require monitoring of renal function during treatment

• Amphotericin B 3

  • Significant nephrotoxic potential
  • Requires close monitoring of renal function
  • Should be used with care in patients with reduced renal function

• Other antimicrobials:

  • Vancomycin (especially at high doses)
  • Foscarnet 1
  • Certain β-lactam antibiotics (causing interstitial nephritis)

Anti-inflammatory Drugs

• NSAIDs (including COX-2 inhibitors) 1
  • Alter intrarenal hemodynamics
  • Particularly harmful in patients with pre-existing kidney disease
  • Should be avoided in patients with residual kidney function

Chemotherapeutic Agents

• Cisplatin 4

  • Direct tubular toxicity
  • Cumulative dose-related nephrotoxicity

• Ifosfamide 5

  • Can cause proximal tubular dysfunction
  • May lead to Fanconi syndrome

Immunosuppressants

• Cyclosporine 4

  • Causes vasoconstriction and reduced GFR
  • Dose-dependent nephrotoxicity

• Tacrolimus

  • Similar mechanism to cyclosporine

Contrast Media

• Intravenous/intra-arterial contrast dyes 1
  • Risk increases with pre-existing kidney disease
  • Particularly problematic in diabetic nephropathy

Medications Affecting Renal Hemodynamics

• ACE inhibitors and ARBs 1

  • Can cause functional changes in GFR
  • Risk increases in volume depletion or bilateral renal artery stenosis
  • May be protective in some conditions despite causing creatinine elevation

• "Triple whammy" combination 1:

  • ACE inhibitors/ARBs
  • Diuretics
  • NSAIDs
  • This combination significantly increases AKI risk

Other Nephrotoxic Substances

• Heavy metals:

  • Lead
  • Mercury
  • Cadmium

• Herbal products (certain types)

• Recreational drugs (e.g., cocaine)

• Industrial chemicals (e.g., carbon tetrachloride)

Mechanisms of Nephrotoxicity

Nephrotoxic substances can damage the kidneys through several mechanisms 1, 6, 7:

1. Direct tubular toxicity - Aminoglycosides, cisplatin, amphotericin B
2. Altered renal/glomerular hemodynamics - NSAIDs, ACE inhibitors, ARBs
3. Acute interstitial nephritis - β-lactam antibiotics, NSAIDs
4. Crystal nephropathy - Acyclovir, certain sulfonamides
5. Thrombotic microangiopathy - Some chemotherapeutic agents

Risk Factors for Nephrotoxicity

Factors that increase risk of nephrotoxic injury 1:

• Pre-existing kidney disease
• Advanced age
• Volume depletion
• Multiple nephrotoxic medications used simultaneously
• Diabetes mellitus
• Heart failure

Prevention Strategies

To reduce nephrotoxicity risk 1:

• Use potentially nephrotoxic medications only when necessary and for the shortest duration possible
• Adjust dosing based on kidney function
• Monitor kidney function regularly during treatment with nephrotoxic drugs
• Maintain adequate hydration, especially with contrast media
• Avoid combinations of nephrotoxic agents when possible
• Consider alternative non-nephrotoxic medications when available

Monitoring for Nephrotoxicity

Early detection of kidney injury requires 6, 7, 8:

• Regular monitoring of serum creatinine and blood urea nitrogen
• Assessment of urine output
• Consideration of newer biomarkers (KIM-1, Cystatin C, NGAL) for earlier detection of injury
• Monitoring of electrolytes, particularly potassium, calcium, and magnesium

Understanding these nephrotoxic substances and their mechanisms of injury is crucial for preventing acute kidney injury and preserving long-term kidney function.