Related Experiment Videos
Risk factors for amphotericin B-induced nephrotoxicity
1University of California, San Francisco, Department of Clinical Pharmacy/School of Pharmacy, 521 Parnassus Avenue, Room C-152, San Francisco, CA 94143-0622, USA.
Abstract:
The association of amphotericin B with nephrotoxicity is well known, but risk factors for this complication are not well characterized. One hundred and seventy-eight patients who received > 3 days of intravenous amphotericin B and a minimal total cumulative dose > 100 mg were reviewed retrospectively. The mean age, average cumulative dose of amphotericin B and duration of therapy were 46 +/- 22 years, 536 +/- 547 mg and 16.6 +/- 8.2 days, respectively. Eighty-six percent of patients received amphotericin B for empirical therapy of febrile neutropenia. Various definitions of nephrotoxicity were used; these were as follows (the incidence of nephrotoxicity as determined by the given definition is given in parentheses): definition 1, a change in creatinine of > 46 mumol/L over baseline (50%); definition 2, a doubling of creatinine over baseline (49%); definition 3, a change in creatinine of > 92 mumol/L (29%); definition 4, a doubling and/or a change in creatinine of > 92 mumol/L (49%); definition 5, an increase in creatinine to > 230 mumol/L (8%). Multivariate analysis showed that nephrotoxicity was associated with a greater cumulative dose of amphotericin B and receipt of concomitant nephrotoxic drugs for all definitions (P < 0.05). In those patients who experienced severe nephrotoxicity (creatinine increased to > 230 mumol/L), cyclosporin therapy was the most significant risk factor (odds ratio 18.8, P = 0.022). Haemodialysis was necessary in one patient, but multiple concomitant risk factors for renal dysfunction were present. No patient experienced irreversible nephrotoxicity. These findings allow for stratification of patients at risk for amphotericin B-induced nephrotoxicity and rational use of alternative agents.
Insights
Amphotericin B can cause kidney damage, with higher doses and other medications increasing risk. Cyclosporine is a key factor in severe cases, but no patients had permanent kidney damage in this study.
Area of Science:
- Nephrology
- Infectious Diseases
- Clinical Pharmacology
Background:
- Amphotericin B is a critical antifungal agent.
- Nephrotoxicity is a known complication of amphotericin B therapy.
- Risk factors for amphotericin B-induced nephrotoxicity require further characterization.
Purpose of the Study:
- To identify risk factors associated with amphotericin B-induced nephrotoxicity.
- To evaluate the incidence of nephrotoxicity using various definitions.
- To inform clinical practice regarding the safe use of amphotericin B.
Main Methods:
- Retrospective review of 178 patients receiving intravenous amphotericin B for >3 days and >100 mg cumulative dose.
- Assessment of nephrotoxicity using five distinct definitions based on serum creatinine changes.
- Multivariate analysis to determine independent risk factors for nephrotoxicity.
Main Results:
- Nephrotoxicity incidence varied by definition, ranging from 8% to 50%.
- Increased cumulative amphotericin B dose and concurrent nephrotoxic drug use were significant risk factors across all definitions.
- Cyclosporine therapy emerged as a strong predictor of severe nephrotoxicity (OR 18.8, P=0.022).
Conclusions:
- Higher cumulative doses of amphotericin B and concomitant nephrotoxic medications increase the risk of kidney injury.
- Cyclosporine use is a significant risk factor for severe amphotericin B-induced nephrotoxicity.
- While amphotericin B can cause transient renal dysfunction, irreversible damage was not observed in this cohort, suggesting careful patient selection and monitoring are key.