Novos biomarcadores endoteliais, inflamatórios e renais em pacientes com HIV/AIDS e Histoplasmose disseminada progressiva

Abstract

Progressive disseminated histoplasmosis (PDH) is a high-mortality opportunistic infection in people living with HIV/AIDS (PLWHA), associated with acute kidney injury (AKI) and hemophagocytic lymphohistiocytosis (HLH). This study investigated the role of novel biomarkers — vascular cell adhesion protein-1 (VCAM-1), syndecan-1, angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), neutrophil gelatinase-associated lipocalin (NGAL), and nephrin — in PLWHA with PDH, and evaluated mortality as well as the incidence of AKI and HLH. A mixed-cohort study was conducted at the São José Hospital of Infectious Diseases in Fortaleza, Ceará, including PLWHA hospitalized with PDH between March 2023 and May 2024. A case–control study was conducted to compare biomarker levels among PLWHA with PDH, PLWHA without PDH, and healthy controls. Data were analyzed using appropriate statistical tests: Chi-square, Fisher’s exact test, Welch’s t-test, Mann–Whitney, analysis of variance (ANOVA), Kruskal– Wallis, Tukey, Dunn, multivariate logistic regression, and Cox regression. The cohort included 61 PLWHA with PDH (78.7% male; 41.0 ± 11.4 years), while the case–control study comprised 34 PLWHA with PDH (76.5% male; 37.4 ± 9.0 years), 13 PLWHA without PDH (76.9% male; 38.5 ± 14.4 years), and 20 healthy controls (70.0% male; 31.7 ± 10.6 years). The incidences of AKI and HLH were 89.7% and 26.2%, respectively. Thrombocytopenia (p = 0.028) and elevated levels of aspartate aminotransferase (AST) (p = 0.009), direct bilirubin (DB) (p = 0.002), lactate dehydrogenase (LDH) (p = 0.006), and Ang-2 (p = 0.011) were associated with AKI. Lower CD8+ T-cell counts (p = 0.016), and total calcium (t-Ca) levels (p = 0.044) were

associated with HLH. Overall mortality was 24.6%, associated with higher levels of C- reactive protein (CRP) (p = 0.001), AST (p = 0.005), DB (p = 0.017), and LDH (p =

0.011), as well as lower t-Ca levels (p = 0.003). Significant differences were observed among PLWHA with PDH, PLWHA without PDH, and healthy controls regarding nephrin, VCAM-1, syndecan-1, and Ang-1 (all p < 0.001), as well as Ang-2 (p = 0.002). This study highlights the potential of AST, DB, CRP, LDH, and Ang-2 as biomarkers for PDH evaluation.