Severe Acute Kidney Injury in HIV-Associated Disseminated Histoplasmosis: Clinical Predictors and the Emerging Role of Angiopoietin-2

Acute kidney injury (AKI) is a frequent, life-threatening complication in people living with HIV (PLWH), particularly those with disseminated histoplasmosis (DH), yet the determinants of severe AKI and the role of endothelial dysfunction remain poorly understood. We assessed the incidence, predictors, and biomarker profile of stage 3 AKI in PLWH hospitalized with DH. In this prospective cohort study at a tertiary infectious diseases center in Northeastern Brazil, adults with probable or proven DH were enrolled, and AKI was defined by Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Kidney injury, inflammatory, and endothelial biomarkers, including angiopoietin-2 (Ang-2), were measured early in hospitalization, and predictors were identified using least absolute shrinkage and selection operator (LASSO)-based multivariable logistic regression. Of 58 patients, 24 (41.4%) developed stage 3 AKI, which was associated with intensive care admission, mechanical ventilation, vasoactive drugs, and in-hospital mortality (54.2% vs. 2.9%, p < 0.001) and with lower body mass index (BMI), hepatomegaly, circulating Histoplasma capsulatum-like yeasts, higher inflammatory and liver injury markers, and higher Ang-2. Only BMI remained independently associated: each 1 kg/m2 increase was associated with lower odds of stage 3 AKI (odds ratio 0.77; 95% confidence interval 0.60–0.95; p = 0.024). The Ang-2 association suggests that endothelial dysfunction may contribute to severe AKI and warrants further study for early risk stratification.