Does Linezolid Increase Creatinine?
Linezolid does not directly increase serum creatinine through nephrotoxicity in the vast majority of patients, as the pharmacokinetics of the parent drug are not altered by renal function and no dose adjustment is required for renal insufficiency. 1, 2
Mechanism and Renal Safety Profile
- The FDA-approved labeling explicitly states that "the pharmacokinetics of the parent drug, linezolid, are not altered in patients with any degree of renal insufficiency" 1
- Total apparent oral clearance of linezolid remains stable across all levels of renal function, ranging from 92.5 to 109.6 ml/min in subjects not requiring dialysis 2
- No dose adjustment is recommended for patients with renal insufficiency based on pharmacokinetic data 1, 2
Rare Cases of Acute Kidney Injury
While linezolid is not considered nephrotoxic, isolated case reports document acute interstitial nephritis:
- A kidney transplant patient developed acute renal failure 8 days after starting linezolid, with serum creatinine rising from 136 to 221 µmol/L, confirmed by biopsy showing interstitial nephritis 3
- An 88-year-old woman developed acute interstitial nephritis on day 7 of linezolid therapy as part of DRESS syndrome (drug rash with eosinophilia and systemic symptoms), with marked creatinine elevation 4
- Both cases resolved after linezolid discontinuation and corticosteroid therapy 3, 4
Important Metabolite Accumulation
- While the parent drug clearance is unchanged, the two primary metabolites of linezolid accumulate in patients with renal insufficiency, with accumulation increasing proportionally to severity of renal dysfunction 1
- In severe renal impairment (creatinine clearance 10-30 mL/min), metabolite A AUC increased to 56.5 µg·h/mL (compared to 7.6 in healthy subjects) and metabolite B to 203 µg·h/mL (compared to 30.5) 1
- The clinical significance of metabolite accumulation remains unknown 1
Monitoring Recommendations
- Monitor complete blood counts at least twice weekly in patients with renal insufficiency receiving linezolid for >2 weeks, as thrombocytopenia occurs significantly more frequently (64.7% vs 35.6%) in this population 5
- Watch for signs of DRESS syndrome (rash, eosinophilia, facial edema) which may herald acute interstitial nephritis 4
- Consider therapeutic drug monitoring in septic patients with renal dysfunction, as trough levels may be elevated despite unchanged clearance of parent drug 6
Clinical Context from Guidelines
- The American Thoracic Society guidelines for drug-resistant tuberculosis note that linezolid's toxicity is primarily hematologic and mitochondrial (inhibition of protein synthesis), not renal 7
- Linezolid's mechanism of toxicity involves binding to human mitochondria, which explains peripheral neuropathy and bone marrow suppression rather than nephrotoxicity 7
Key Pitfalls to Avoid
- Do not empirically reduce linezolid dose in renal insufficiency - this is not supported by pharmacokinetic data and may lead to treatment failure 1, 2
- Do not confuse metabolite accumulation (which occurs) with parent drug accumulation (which does not occur) 1
- Recognize that acute interstitial nephritis from linezolid is exceedingly rare but possible, particularly in the context of hypersensitivity reactions 3, 4
- Approximately 30% of a linezolid dose is removed by a 3-hour hemodialysis session, so administer linezolid after hemodialysis 1