Drug-Induced Nephrotoxicity Caused by Amphotericin B Lipid Complex and Liposomal Amphotericin B: A Review and Meta-Analysis

Immunology Research Program, Department of Infectious Diseases, Infection Control and Employee Health, The Anderson Cancer Center, Houston, Texas 77030, USA.
Medicine (Impact Factor: 5.72). 07/2010; 89(4):236-44. DOI: 10.1097/MD.0b013e3181e9441b
Source: PubMed


Lipid preparations of amphotericin B, commonly used to treat fungal infections, have been demonstrated to have reduced nephrotoxicity compared to conventional amphotericin B. However, to our knowledge, a comprehensive comparison of nephrotoxicity induced by different lipid preparations of amphotericin B has not been performed. We conducted a meta-analysis to evaluate nephrotoxicity associated with amphotericin B lipid complex (ABLC) and liposomal amphotericin B (L-AmB). We searched the PubMed MEDLINE database and abstracts presented at key scientific meetings, and identified 11 studies reported between 1995 and 2008 that compared nephrotoxicity resulting from the use of these agents. Eight of the 11 studies were included in the meta-analysis. The Cochran-Mantel-Haenszel test was used to determine odds ratio (OR) and relative risk (RR), and the Breslow-Day test was used to analyze homogeneity of ORs across different studies. Analysis of all 8 studies (n = 1160) included in the meta-analysis showed an increased probability of nephrotoxicity in patients treated with ABLC versus L-AmB (OR, 1.75; RR, 1.55), but there was a significant lack of homogeneity across these studies (p < 0.001). After excluding the study by Wingard et al, the probability of experiencing nephrotoxicity was more similar between the 2 AmB lipid preparations (OR, 1.31; RR, 1.24; n = 916), particularly when the analysis included only the salvage patient population reported by Hachem et al (OR, 1.12; RR, 1.09; n = 839); the 7 remaining studies were more homogenous by Breslow-Day test (p = 0.054). Our results suggest that nephrotoxicity is generally similar for ABLC and L-AmB in patients receiving antifungal therapy and prophylaxis.


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    • "Due to the probability that the pattern of nephrotoxicity of AmB lipid-based formulations is transitory , the time point of assessing nephrotoxicity (for example, 1 vs. 6 weeks) is a critical factor in determining the rate of nephrotoxicity. In conclusion, these authors suggest that ABLC or L-AmB can be given to immunocompromised patients for the treatment or prophylaxis of invasive fungal infections with comparable efficacy and safety [83]. Martino believed that the differences identified in the Wingard et al. trial can be attributed to the different pharmacokinetic and pharmacodynamic profiles of ABLC and L-AmB [81] . "
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