Is ketorolac safe in patients with chronic kidney disease?

Ketorolac is NOT Safe in CKD and Should Be Avoided

Ketorolac should be avoided in patients with chronic kidney disease due to significant nephrotoxicity risk, particularly in those with impaired renal function. The FDA label explicitly contraindicates ketorolac in patients with advanced renal impairment and warns that it should be used with extreme caution in any patient with reduced renal function 1. Major guidelines consistently recommend avoiding NSAIDs, including ketorolac, in CKD patients.

Guideline-Based Contraindications

NSAIDs should be avoided in patients with eGFR <30 mL/min/1.73 m² and prolonged therapy is not recommended when eGFR <60 mL/min/1.73 m² 2. The KDOQI guidelines specifically state that NSAIDs should not be used in people taking lithium or RAS blocking agents (ACE inhibitors/ARBs), which are standard therapy for most CKD patients with albuminuria 2.

For acute gout management in CKD—one of the few scenarios where NSAIDs might be considered—KDIGO 2024 explicitly recommends that low-dose colchicine or glucocorticoids are preferable to NSAIDs 2. This reflects the consensus that NSAIDs pose unacceptable risk in the CKD population.

Mechanism of Harm in CKD

The FDA label explains that ketorolac and its metabolites are eliminated primarily by the kidneys, resulting in diminished clearance in patients with reduced creatinine clearance 1. This creates a dangerous cycle: impaired elimination leads to drug accumulation, which further compromises renal function.

Ketorolac inhibits prostaglandin-mediated vasodilation, which is critical for maintaining renal perfusion in CKD patients 1, 3. In patients where renal prostaglandins have a compensatory role in maintaining renal perfusion—including those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly—NSAIDs cause dose-dependent reduction in renal blood flow that may precipitate overt renal decompensation 1.

Evidence of Renal Toxicity

Research demonstrates ketorolac's particular nephrotoxic potential:

• Ketorolac shows a 2-fold increased risk of acute renal failure compared to opioids when used for >5 days (adjusted rate ratio 2.08,95% CI 1.08-4.00) 4
• Population-based studies found ketorolac associated with a 2.54-fold increased risk of chronic kidney disease (95% CI 1.45-4.44) compared to non-use, the highest risk among individual NSAIDs studied 5
• Case reports document irreversible renal failure following ketorolac administration, even in patients with initially normal renal function 3, 6

The FDA label reports that acute renal failure, interstitial nephritis, and nephrotic syndrome have all been associated with ketorolac use 1.

Clinical Decision Algorithm

For any CKD patient (eGFR <60 mL/min/1.73 m²):

• Do NOT use ketorolac for any indication 2, 1
• If eGFR <30 mL/min/1.73 m²: ketorolac is absolutely contraindicated 2, 1
• If eGFR 30-60 mL/min/1.73 m²: avoid ketorolac; use alternative analgesics 2

Alternative analgesic options in CKD:

• Opioids with dose reduction when eGFR <60 mL/min/1.73 m² and careful use when eGFR <15 mL/min/1.73 m² 2
• Acetaminophen (no dose adjustment needed for renal function)
• For acute gout: low-dose colchicine or glucocorticoids 2

Critical Pitfalls to Avoid

Do not assume short-term use is safe. While ketorolac is typically limited to ≤5 days, even brief exposure in vulnerable CKD patients can precipitate acute-on-chronic kidney injury 7, 6. The postoperative setting—where ketorolac is commonly used—creates additional risk through third-spacing of fluid and renal hypoperfusion 6.

Do not use ketorolac in patients on RAS inhibitors (ACE-I/ARBs). Since RAS blockade is standard therapy for CKD patients with albuminuria 2, and guidelines explicitly warn against combining NSAIDs with RAS blocking agents 2, this effectively excludes most CKD patients from ketorolac use.

Elderly patients with CKD face compounded risk as they are specifically identified as high-risk for NSAID nephrotoxicity 1, 7, and age-related GFR decline may not be fully captured by creatinine-based estimates 1.

The evidence is unequivocal: ketorolac poses unacceptable nephrotoxic risk in CKD patients and safer alternatives exist for all clinical scenarios where it might be considered.