Is ketorolac (Nonsteroidal Anti-Inflammatory Drug (NSAID)) safe in patients with Chronic Kidney Disease (CKD)?

Ketorolac Is Not Safe in Chronic Kidney Disease

Ketorolac is contraindicated in patients with chronic kidney disease due to its high risk of causing acute kidney injury and worsening kidney function. 1

Mechanism of Kidney Damage with Ketorolac

• Ketorolac, like other NSAIDs, inhibits prostaglandin synthesis, which plays a critical role in maintaining renal perfusion, especially in patients with already compromised kidney function 2
• In CKD patients, renal prostaglandins have a compensatory role in maintaining renal blood flow; inhibition by ketorolac can cause a dose-dependent reduction in renal perfusion, precipitating overt renal decompensation 1
• Ketorolac can cause several forms of kidney damage including acute kidney injury, interstitial nephritis, and nephrotic syndrome 1

FDA Contraindications and Warnings

• Ketorolac is explicitly contraindicated in patients with "advanced renal impairment" according to the FDA drug label 1
• The FDA label specifically states that ketorolac "should be used with caution in patients with impaired renal function or a history of kidney disease because it is a potent inhibitor of prostaglandin synthesis" 1
• Patients with underlying renal insufficiency are at increased risk of developing acute renal decompensation or failure with ketorolac use 1

Evidence of Harm in CKD Patients

• Case reports have documented reversible acute renal failure following ketorolac therapy in patients with pre-existing chronic renal failure 3, 4
• A population-based case-control study found that ketorolac was associated with a significantly increased risk of CKD (adjusted OR: 2.54; 95% CI: 1.45-4.44) compared to non-use 5
• Elderly patients with CKD are particularly vulnerable to ketorolac nephrotoxicity due to age-related changes in drug metabolism and excretion 6

Guidelines on NSAIDs in CKD

• The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend avoiding nephrotoxic medications such as NSAIDs in patients with CKD 2
• The Acute Disease Quality Initiative (ADQI) consensus report specifically mentions withholding NSAIDs during the persistent or recovery phase of acute kidney disease 2
• KDOQI guidelines specifically list NSAIDs as medications to avoid in people with GFR < 30 ml/min/1.73 m² 2

Risk Factors That Increase Nephrotoxicity

• The risk of ketorolac nephrotoxicity is significantly increased when combined with:
  • Other nephrotoxic medications 2
  • ACE inhibitors or ARBs (the "triple whammy" effect when combined with diuretics) 2
  • Volume depletion or dehydration 6
  • Heart failure 1
  • Liver dysfunction 1
  • Advanced age 1, 6

Alternative Pain Management Approaches for CKD Patients

• For pain management in CKD patients, consider:
  • Acetaminophen (with appropriate dose adjustment) 7
  • Careful use of opioids with dose adjustment based on GFR 2
  • Non-pharmacological pain management strategies 7

Clinical Recommendation

Ketorolac should be avoided in all stages of CKD due to the high risk of worsening kidney function and precipitating acute kidney injury. 1, 5 The risks of using ketorolac in CKD patients far outweigh any potential short-term analgesic benefits, especially when safer alternatives are available.