Drug-Induced Nephrotoxicity Caused by Amphotericin B Lipid Complex and Liposomal Amphotericin B

Abstract

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.

Ventajas y desventajas de los distintos tipos de anfotericina en pediatría: revisión de la bibliografía

“…5,15 Sin embargo, esos resultados no son concluyentes. 9,11,[15][16][17] Tres aspectos a tener en cuenta son: la definición de nefrotoxicidad según los diferentes autores; 20 que la creatininemia puede subestimar el filtrado glomerular 25 y que no hay estudios a largo plazo sobre la evolución del compromiso renal.…”

Renal Handling of Amphotericin B and Amphotericin B-Deoxycholate and Potential Renal Drug-Drug Interactions with Selected Antivirals

“…Although the new lipid formulations of AmB have a lower frequency of nephrotoxicity in comparison with AmB-DOC, they all exhibit this adverse effect in a considerable number of patients (10,11,12). AmB most likely produces renal injury by a variety of mechanisms; however, the exact nephrotoxic mechanism remains an open question (2,13).…”

Subclinical tumor lysis-like syndrome during treatment of visceral leishmaniasis with low-dose intermittent liposomal amphotericin B

“…Despite the improved safety features, patients receiving L-AmB may still experience infusion reactions such as fever, chills and rigors and renal toxicity. A recent meta-analysis demonstrated that the probability of experiencing nephrotoxicity during treatment with daily L-AmB (doses 3-10 mg/kg) for invasive fungal infections (IFIs) in patients with hematological malignancies ranged from 2.8 to 32% [9].…”