Risk factors for Amphotericin B-associated nephrotoxicity.
OBJECTIVE
A case-control study was performed to identify and quantify risk factors for amphotericin B-associated nephrotoxicity.


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).


CONCLUSIONS
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.
Fisher
M A
MA
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia.
Talbot
G H
GH
Maislin
G
G
McKeon
B P
BP
Tynan
K P
KP
Strom
B L
BL
D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000009:adverse effects*; D016022:Case-Control Studies; D003404:Creatinine / Q000097:blood; D004232:Diuretics / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced* / Q000453:epidemiology; D008875:Middle Aged; D010414:Pennsylvania; D012307:Risk Factors
D004232:Diuretics; D000666:Amphotericin B; D003404:Creatinine