Antifungal agents and the kidney: pharmacokinetics, clinical nephrotoxicity, and interactions

Introduction Invasive fungal infections continue to be important causes of morbidity and mortality in severely ill and immunocompromised patient populations. The past three decades have seen a considerable expansion in antifungal drug research, resulting in the clinical development of different classes of antifungal agents with different pharmacologic properties. Among drug-specific characteristics of antifungal agents, renal disposition and nephrotoxicity are important clinical considerations as many patients requiring antifungal therapy have compromised organ functions or are receiving other potentially nephrotoxic medications. Areas covered The present article reviews incidence, severity and mechanisms of nephrotoxicity associated with antifungal agents used for prevention and treatment of invasive fungal diseases by discussing distribution, metabolism, elimination and drug-related adverse events in the context of safety data from phase II and III clinical studies. Expert opinion Based on the available data amphotericin B deoxycholate has the highest relative potential for nephrotoxicity, followed by the lipid formulations of amphotericin B, and, to a much lesser extent and by indirect mechanisms, the antifungal triazoles.

Automated summary

Invasive fungal infections remain a significant concern for severely ill and immunocompromised patients, leading to an increase in research on antifungal drugs. Nephrotoxicity is an important consideration in the use of antifungal agents, particularly for patients with compromised organ functions or receiving other potentially nephrotoxic medications. Amphotericin B deoxycholate is identified as having the highest potential for nephrotoxicity, followed by lipid formulations of amphotericin B and the antifungal triazoles to a much lesser extent.