Is Toradol (Ketorolac) Nephrotoxic?
Yes, ketorolac is nephrotoxic and can cause acute renal failure, particularly in patients with risk factors such as pre-existing renal impairment, volume depletion, heart failure, advanced age, or concurrent use of other nephrotoxic medications. 1
Mechanism of Nephrotoxicity
Ketorolac causes renal toxicity through inhibition of prostaglandin synthesis, which is critical for maintaining renal perfusion in certain clinical states. 1, 2
Prostaglandin-dependent renal perfusion: In patients with compromised renal blood flow, prostaglandins play a compensatory vasodilatory role. Ketorolac blocks this protective mechanism, leading to dose-dependent reduction in renal blood flow and potential acute renal decompensation. 1
Direct renal injury: Long-term NSAID administration, including ketorolac, has resulted in renal papillary necrosis and other structural renal injury. 1
Reported complications: Acute renal failure, interstitial nephritis, and nephrotic syndrome have all been documented with ketorolac use. 1
FDA Contraindications and Warnings
The FDA label explicitly contraindicates ketorolac in specific renal scenarios: 1
Absolute contraindication: Advanced renal impairment (elevated serum creatinine indicating advanced disease) 1
Absolute contraindication: Patients at risk for renal failure due to volume depletion 1
Use with extreme caution: Patients with impaired renal function or history of kidney disease, as ketorolac is a potent prostaglandin synthesis inhibitor 1
High-Risk Patient Populations
The following patients are at greatest risk for ketorolac-induced nephrotoxicity: 1
- Impaired baseline renal function
- Heart failure
- Liver dysfunction
- Elderly patients
- Those taking diuretics and ACE inhibitors concurrently
- Volume-depleted states (postoperative third-spacing, dehydration)
Clinical Evidence of Nephrotoxicity
Case series consistently demonstrate reversible acute renal failure with ketorolac:
Three patients developed acute renal failure and/or hyperkalemia after ketorolac administration, with reversibility in two cases after drug discontinuation. All had pre-existing conditions rendering them susceptible to NSAID-related renal complications. 2
Six patients (mean age 58 years, five with cardiovascular disease) developed renal insufficiency with serum creatinine rising from mean 106 μmol/L (1.2 mg/dL) to peak 256 μmol/L (2.9 mg/dL). Recovery occurred after mean 2.3 days following discontinuation. 3
Three additional cases showed acute renal failure and hyperkalemia after moderate ketorolac doses for postsurgical pain, with transient dysfunction improving after drug cessation. 4
Critical Clinical Pitfalls
Postoperative use is particularly hazardous: Nearly 90% of reported ketorolac nephrotoxicity cases occurred in postoperative patients, where third-spacing of fluids causes renal hypoperfusion. 5
The analgesic potency may obscure the NSAID risk: Because ketorolac is primarily marketed as an analgesic, its potent prostaglandin synthesis inhibition may not be adequately recognized, leading to inappropriate use in high-risk patients. 2
Dosing adjustments are mandatory in renal impairment: Since ketorolac and its metabolites are eliminated primarily by the kidneys, reduced creatinine clearance results in diminished drug clearance, necessitating dose adjustment or avoidance. 1
Monitoring Requirements
When ketorolac must be used despite renal concerns: 1
- Close monitoring of urine output and renal function parameters is essential 5
- Patients with underlying renal insufficiency require careful risk-benefit assessment before administration 1
- Elderly patients or those with baseline renal dysfunction need dosing interval adjustments or complete avoidance 5
Duration and Dosage Limitations
The FDA mandates strict duration limits: Treatment should not exceed 5 days, as risk of serious adverse events (including nephrotoxicity) increases markedly with prolonged use, especially at high doses and in elderly patients. 6
Comparison to Other Analgesics
Unlike ketorolac, acetaminophen is preferred for non-inflammatory pain in patients with kidney dysfunction, as it lacks the prostaglandin-mediated renal effects. 7