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Risk factors for Amphotericin B-associated nephrotoxicity
M A Fisher1, G H Talbot, G Maislin
1Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia.
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.
Insights
Higher average daily doses of amphotericin B, diuretic use, and abnormal baseline renal function significantly increase nephrotoxicity risk. These findings help clinicians assess amphotericin B therapy risks for fungal infections.
Area of Science:
- Pharmacology
- Nephrology
- Infectious Diseases
Background:
- Amphotericin B is a critical antifungal agent.
- Nephrotoxicity is a significant adverse effect of amphotericin B therapy.
- Identifying risk factors is crucial for patient safety.
Purpose of the Study:
- To identify and quantify risk factors associated with amphotericin B-induced nephrotoxicity.
- To analyze the relationship between dosing variables and nephrotoxicity.
- To evaluate other potential risk factors for kidney damage.
Main Methods:
- A case-control study comparing 35 patients with amphotericin B nephrotoxicity to 60 controls.
- Analysis of amphotericin B dosing variables and other risk factors using logistic regression.
- Quantification of risk associated with dose increments, duration, weight, diuretic use, and baseline creatinine.
Main Results:
- Higher average daily doses of amphotericin B were significantly associated with increased nephrotoxicity risk.
- Diuretic use and abnormal baseline serum creatinine were identified as significant risk factors.
- Increased patient weight showed a protective effect against nephrotoxicity.
Conclusions:
- Higher average daily doses, diuretic use, and abnormal baseline renal function are key risk factors for amphotericin B nephrotoxicity.
- These findings support the development of protective interventions.
- Clinicians can use this data to better assess the risk-benefit ratio of amphotericin B treatment.