Is Tylenol (Acetaminophen) Nephrotoxic?
Acetaminophen is primarily hepatotoxic rather than nephrotoxic at therapeutic doses, but it can cause acute kidney injury through acute tubular necrosis in overdose situations (>2,000 mg/kg) or in vulnerable populations, and does NOT cause chronic analgesic nephropathy when used alone. 1, 2
Nephrotoxicity Profile
At Therapeutic Doses (≤4,000 mg/day)
Acetaminophen is NOT considered nephrotoxic in healthy individuals at recommended doses (maximum 4,000-6,000 mg daily). 1
The primary toxicity concern is hepatotoxicity, not nephrotoxicity, which is why guidelines list "hepatotoxicity" as the main caution rather than renal toxicity. 1
Acetaminophen does NOT cause classic analgesic nephropathy when taken alone, unlike NSAIDs which carry significant renal toxicity warnings. 3, 2
High-Risk Populations at Therapeutic Doses
Acetaminophen CAN cause acute kidney injury at therapeutic doses in glutathione-depleted patients:
- Chronic alcohol users (glutathione depletion) 4
- Malnourished or fasting patients (glutathione depletion) 4
- Patients taking P-450 enzyme inducers (anticonvulsants) 4
- Patients with pre-existing kidney disease (chronic glomerulonephritis, Balkan endemic nephropathy) 5, 6
In Overdose Situations
Acute renal failure occurs in <2% of all acetaminophen poisonings and 10% of severely poisoned patients through acute tubular necrosis (ATN). 4
Overdose threshold: >2,000 mg/kg produces highly reactive quinone metabolites that cause both hepatic and renal toxicity. 2
ATN can occur alone or combined with hepatic necrosis, and azotemia is typically reversible though may worsen over 7-10 days before recovery. 4
Comparison to NSAIDs
This contrasts sharply with NSAIDs, which are explicitly labeled as having "GI and renal toxicity":
Ibuprofen, ketoprofen, diclofenac, mefenamic acid, and naproxen all carry warnings for both GI and renal toxicity at therapeutic doses. 1
NSAIDs cause renal dysfunction through hemodynamic mechanisms (afferent arteriole constriction) even at recommended doses. 1
Clinical Implications
When to Avoid or Use Cautiously
Avoid in patients with chronic alcohol use, malnutrition, or fasting states unless absolutely necessary. 4
Use caution when combining with other nephrotoxic agents (contrast media, antibiotics) in vulnerable patients, as this may worsen renal dysfunction. 5
Monitor renal function in patients with pre-existing kidney disease who require acetaminophen, as they show increased urinary β2-microglobulin excretion (marker of tubular injury) even at therapeutic doses. 6
Acetaminophen Does NOT Require Routine Renal Monitoring
- Unlike aminoglycosides, NSAIDs, and other truly nephrotoxic agents that require baseline and ongoing renal function monitoring, acetaminophen does not require routine kidney function surveillance at therapeutic doses in healthy individuals. 1
Key Pitfall to Avoid
Do not confuse acetaminophen's overdose nephrotoxicity with the chronic analgesic nephropathy caused by combination analgesics (aspirin + acetaminophen) or phenacetin-containing products. Epidemiologic studies have failed to demonstrate chronic renal disease development with acetaminophen alone. 3, 2