Is ketorolac safe for patients with chronic kidney disease (CKD), especially those with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² or on dialysis?

Ketorolac Safety in CKD Patients

Ketorolac is contraindicated in patients with advanced renal impairment (serum creatinine indicating advanced disease) and should be avoided in CKD patients, particularly those with eGFR <60 mL/min/1.73 m², due to significant risk of acute kidney injury and further renal deterioration. 1

FDA-Mandated Contraindications and Warnings

• Ketorolac is explicitly contraindicated in patients with serum creatinine concentrations indicating advanced renal impairment, as stated in the FDA drug label 1
• The drug should be used with extreme caution in patients with impaired renal function or 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 when exposed to ketorolac 1
• Ketorolac and its metabolites are eliminated primarily by the kidneys, resulting in diminished clearance in patients with reduced creatinine clearance 1

Clinical Evidence of Nephrotoxicity in CKD

• In patients with pre-existing chronic kidney disease undergoing total knee arthroplasty, ketorolac in local infiltration analgesia increased acute kidney injury incidence from 2.0% to 12.7% (P=0.041), representing a more than 6-fold increase in risk 2
• Patients with normal renal function showed no elevated AKI risk with ketorolac (2.0% vs 1.9%, P=1.0), demonstrating that the nephrotoxic effect is specifically pronounced in those with baseline renal impairment 2
• Acute renal failure has been reported after ketorolac treatment but is usually reversible after discontinuation, though this reversibility cannot be guaranteed in patients with pre-existing CKD 3

Guideline Recommendations for Nephrotoxin Avoidance

• For patients with eGFR <60 mL/min/1.73 m², exposure to nephrotoxins including nonsteroidal anti-inflammatory drugs should be minimized, as recommended by the American Diabetes Association 4
• For symptomatic treatment of acute gout in CKD, low-dose colchicine or intra-articular/oral glucocorticoids are preferable to NSAIDs, according to the 2024 KDIGO guidelines 4

Mechanism of Renal Injury

• NSAIDs cause dose-dependent reduction in prostaglandin formation and secondarily reduce renal blood flow, which may precipitate overt renal decompensation in patients whose renal prostaglandins play a compensatory role in maintaining renal perfusion 1
• Long-term NSAID administration has resulted in renal papillary necrosis and other renal injury, with reports of acute renal failure, interstitial nephritis, and nephrotic syndrome associated with ketorolac use 1

High-Risk Patient Populations

• Patients at greatest risk include those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly 1
• Postoperative ketorolac therapy should be avoided in patients with conditions that predispose to NSAID nephrotoxicity, particularly when significant third-spacing of fluid and renal hypoperfusion may occur 5
• Elderly patients or patients with underlying renal insufficiency must have dosing interval adjustment, or the medication should be avoided altogether 5

Critical Pitfalls to Avoid

• Do not assume that short-term use is safe in CKD patients—even brief exposure (≤5 days) carries elevated risk in vulnerable populations 3
• Do not use ketorolac in patients on dialysis or with eGFR <30 mL/min/1.73 m², as this represents advanced renal impairment per FDA contraindications 1
• Do not combine ketorolac with other nephrotoxic agents (ACE inhibitors, diuretics, contrast media) without extreme caution and close monitoring 1
• Volume depletion must be corrected before any consideration of ketorolac use, as hypovolemia dramatically increases nephrotoxicity risk 6

Safer Alternatives for Pain Management in CKD

• Acetaminophen remains the first-line analgesic for mild-to-moderate pain in CKD patients, with no dose adjustment needed until eGFR <10 mL/min/1.73 m² 4
• Opioids can be used with appropriate dose adjustments based on renal function, though they require careful monitoring for accumulation of active metabolites 3
• For inflammatory conditions, low-dose colchicine or corticosteroids are preferred over NSAIDs in the CKD population 4