The Hidden Cost of Amphotericin: Kidney Injury in Patients with Invasive Fungal Sinusitis

Introduction: Invasive fungal sinusitis (IFS) is a life-threatening condition requiring urgent surgical management and empiric amphotericin B therapy, often initiated before fungal speciation is available. Despite its widespread use and known nephrotoxicity, renal outcomes associated with amphotericin in contemporary IFS populations have not yet been described.

Methods: We performed a single-center retrospective study of adults with IFS from 2018-2025. Creatinine from days 1 to 31 of hospitalization, fungus category, and death or dialysis due to amphotericin within 3 months were evaluated.

Results: 36 patients with IFS were identified from a single center. Among 31 patients who received amphotericin, 20 (64.5%) experienced a mean increase in creatinine after starting amphotericin. Overall, patients experienced a 1.12-fold increase in creatinine after starting amphotericin, and 14 patients experienced a maximum increase of 50% or more. Of the patients whose creatinine rose by 50% or more, 4 (28.6%) had aspergillus. Kidney failure due to amphotericin contributed to death in 2 patients (6.45%), one of whom had aspergillus, and need for dialysis in 1 patient (3.23%). In a multivariable model, chronic kidney disease (CKD) emerged as the only variable independently associated with greater creatinine rise, corresponding to an additional 1.25 mg/dL increase in creatinine (95% CI 0.49–2.01; p=0.0023), after adjustment for fungus type, baseline creatinine, and total amphotericin exposure. The overall model was significant (p=0.034, R2=0.33, Adj. R2=0.21).

Conclusions: Amphotericin therapy for IFS is frequently associated with clinically meaningful kidney injury. While severe outcomes such as dialysis or death are uncommon, they represent significant morbidity. Patients with underlying CKD are at highest risk and warrant heightened monitoring and risk-mitigation strategies when treated with amphotericin. While amphotericin remains a life-saving therapy for many patients with IFS, those with aspergillus infection may benefit from rapid fungal identification and early transition to newer, less nephrotoxic agents.