Risk factors for Amphotericin B-associated nephrotoxicity

Am J Med. 1989 Nov;87(5):547-52. doi: 10.1016/s0002-9343(89)80612-6.


Purpose: A case-control study was performed to identify and quantify risk factors for amphotericin B-associated nephrotoxicity.

Patients and methods: Thirty-five patients receiving intravenous amphotericin B for treatment of proven or suspected fungal infection who developed nephrotoxicity (greater than 100% increase in baseline serum creatinine to a level above the normal range) were compared with 60 control patients receiving amphotericin B who did not develop nephrotoxicity. Amphotericin B dosing variables and other potential risk factors were analyzed in a logistic regression model.

Results: Cases of nephrotoxicity received a significantly higher average daily dose of amphotericin B (0.49 +/- 0.18 mg/kg/day) than did controls (0.34 +/- 0.17 mg/kg/day). In a multivariate model, the risk of nephrotoxicity increased 3.7-fold for each 50-mg increase in total dose for a fixed duration of therapy and patient weight. Risk decreased by a factor of 0.4 for each extra day of therapy for a fixed total dose and weight. An increase in weight was also protective when the two other dosage variables were held constant. Each 0.10 mg/kg/day dose increment was associated with a 1.8-fold (95% confidence interval, 1.2 to 2.7) increase in the risk of nephrotoxicity. Other significant risk factors included diuretic use during amphotericin B therapy (12.5, 1.7 to 94.7), for which a linear dose-response relationship was demonstrated, and an abnormal baseline serum creatinine level (15.4, 1.4 to 173.2).

Conclusion: Risk factors for amphotericin B-associated nephrotoxicity include higher average daily doses (approximately a doubling for each 0.10 mg/kg/day increment), diuretic use, and abnormal baseline renal function. These data suggest possible protective interventions and will aid clinicians in assessing the risk-benefit ratio of amphotericin B therapy for deep fungal infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amphotericin B / adverse effects*
  • Case-Control Studies
  • Creatinine / blood
  • Diuretics / administration & dosage
  • Dose-Response Relationship, Drug
  • Humans
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / epidemiology
  • Middle Aged
  • Pennsylvania
  • Risk Factors


  • Diuretics
  • Amphotericin B
  • Creatinine