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Can we decrease amphotericin nephrotoxicity?
1Grupo de Controle de Infecção Hospitalar, Departamento de Doenças Infecciosas e Parasitárias, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo.
Abstract:
Amphotericin B (AmB) is considered the drug of choice for the treatment of systemic fungal infections. Nephrotoxicity is a major complication associated with its use, and appears to be related to higher cumulative doses, diuretic use, abnormal serum creatinine at baseline, and the use of concomitant nephrotoxic drugs. The two major hypotheses for the pathogenesis of AmB-related nephrotoxicity are direct effects of the drug on epithelial cell membranes and vasoconstriction. During the last few years, some randomized trials have tested different strategies to reduce AmB-induced renal toxicity. These strategies include sodium supplementation, low-dose dopamine, slower infusion rates, the administration of AmB in lipid emulsions, and in lipid formulations. The results of these trials showed that the lipid formulations of AmB significantly reduce nephrotoxicity. Unfortunately, these agents are costly, restricting their use to patients with a high risk of developing renal failure.
Insights
Amphotericin B treats fungal infections but can harm kidneys. Lipid formulations of Amphotericin B significantly reduce this nephrotoxicity, offering a safer treatment option for at-risk patients.
Area of Science:
- Pharmacology
- Nephrology
- Mycology
Background:
- Amphotericin B (AmB) is a primary antifungal agent for systemic infections.
- Nephrotoxicity is a significant adverse effect of AmB, linked to dose, diuretics, baseline creatinine, and co-administered drugs.
- Pathogenesis theories include direct epithelial cell membrane effects and vasoconstriction.
Purpose of the Study:
- To review strategies aimed at mitigating AmB-induced nephrotoxicity.
- To evaluate the efficacy of different AmB administration methods in preventing renal damage.
Main Methods:
- Review of randomized trials testing various AmB nephrotoxicity reduction strategies.
- Comparison of conventional AmB with lipid emulsions and lipid formulations.
Main Results:
- Lipid formulations of Amphotericin B demonstrated a significant reduction in nephrotoxicity compared to conventional AmB.
- Other strategies like sodium supplementation and dopamine showed varied results.
Conclusions:
- Lipid formulations represent a safer alternative for Amphotericin B administration, minimizing renal toxicity.
- High cost of lipid formulations limits their widespread use, reserving them for high-risk individuals.
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