NSAID Renal Adverse Effects

Aka: NSAID Renal Adverse Effects, Nephrotoxicity due to NSAIDs

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II. Epidemiology

  1. NSAIDs are top cause of Kidney injury and Renal Insufficiency in the elderly

III. Physiology

  1. NSAIDs decrease synthesis of renal Prostaglandins
  2. Prostaglandins vasodilate renal vessels
  3. NSAIDs therefore reduce renal Blood Flow

IV. Risk Factors: NSAID related Acute Renal Failure

  1. Elderly
  2. Hypovolemia or Dehydration
  3. Heat Related Illness
  4. Acute illness (e.g. Viral Infection)
  5. Ineffective circulation
    1. Congestive Heart Failure
    2. Cirrhosis
    3. Nephrotic Syndrome
  6. Concurrent medications
    1. ACE Inhibitor
    2. Angiotensin Receptor Blocker (ARB)
    3. Diuretics
    4. SGLT2 Inhibitor

V. Adverse Effects: General Renal effects

  1. NSAID Related Fluid and Electrolyte abnormalities
    1. Edema (may provoke CHF)
    2. Hyperkalemia
  2. Acute Renal Failure
  3. Acute papillary Necrosis

VI. Management: Practice Guidelines for NSAID use in the elderly

  1. Establish a definitive treatment diagnosis
    1. Inflammatory condition (e.g. Rheumatoid Arthritis)
      1. NSAID indicated
      2. COX2 Inhibitor offers no advantage regarding nephrotoxicity
    2. Non-Inflammatory condition
      1. NSAID alternative medication (e.g. Tylenol)
  2. Use the lowest effective dose of NSAIDs for the shortest possible duration
    1. Occasional OTC NSAID (Naproxen or Ibuprofen) may be tolerated
    2. Consider Topical NSAID for localized pain (e.g. Hand Osteoarthritis)
    3. Maintain hydration and monitor for adverse effects (e.g. edema)
  3. Monitoring
    1. Perform baseline Renal Function and repeat at 2 weeks, then every 3-12 months
    2. See NSAIDs for lab monitoring
    3. Creatinine and Serum Potassium
    4. Consider screening for Proteinuria
  4. Choose NSAID with high benefit to risk ratio (e.g. Sulindac)
    1. Understand that no NSAID is considered safest, and all carry a risk for Renal Injury
    2. Good efficacy
    3. Lower renal toxicity
  5. Avoid the most NSAIDS most commonly associated with nephrotoxicity
    1. Ketorolac (Toradol)
    2. Indomethacin
  6. Consider Gastric protection or COX2 Inhibitor
    1. See NSAID Gastrointestinal Adverse Effects
  7. Continue to monitor efficacy and side effects
    1. Do no harm
  8. Avoid combining high risk medications
    1. Never use two different types of systemic NSAIDs together
  9. Avoid NSAIDs in reduced renal perfusion
    1. Avoid NSAIDs with ACE Inhibitors or Angiotensin Receptor Blockers
    2. Avoid NSAIDs with Diuretics
    3. Avoid NSAIDs in Dehydration
  10. Avoid combinations predisposing to Hyperkalemia
    1. Avoid NSAID with Potassium sparing Diuretic
    2. Avoid NSAID with ACE Inhibitor
    3. Avoid NSAID with Trimethoprim-Sulfamethoxazole (especially with ACE Inhibitors)

VII. References

  1. (2022) Presc Lett 29(10): 56

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