#3448 Von Willebrand factor as a predictor of acute kidney injury and hemodialysis requirement in severe leptospirosis: a prospective cohort study

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Abstract Background and Aims Leptospirosis is a zoonotic disease caused by spirochetes of the Leptospira genus. It is globally distributed, with a higher incidence in the Americas, Southeast Asia, Oceania and East Sub-Saharan Africa. The disease exhibits a broad clinical spectrum, ranging from a nonspecific febrile illness to a biphasic course characterized by an initial febrile phase followed by a severe stage with jaundice, acute kidney injury (AKI), conjunctival suffusion, haemorrhagic manifestations, and mortality. AKI is a critical complication, with approximately 30% of affected patients requiring renal replacement therapy. The underlying mechanisms of kidney injury in leptospirosis remain incompletely understood. The literature describes multiple pathogenic pathways, including interstitial nephritis due to direct spirochete invasion, acute tubular necrosis and rhabdomyolysis. Recent studies have identified endothelial biomarkers such as Syndecan-1 and Angiopoietin-2 as potential predictors of AKI and the need for hemodialysis, offering new insights into the pathophysiology of renal involvement in severe leptospirosis. This study aims to evaluate the association between von Willebrand Factor (vWF) and AKI in patients with severe leptospirosis. Method This prospective observational study was conducted in Fortaleza, Brazil, including hospitalized patients diagnosed with severe leptospirosis. Blood and urine samples were collected at hospital admission to measure von Willebrand Factor A2, Angiopoetin-2 and VCAM-1 levels. Patients were stratified into two groups based on the presence of AKI at admission and followed until discharge or death to assess AKI progression and hemodialysis requirements. Results Forty-five patients were included in the study, with a mean age of 39 ± 13 years, of whom 86.7% were male. Acute kidney injury (AKI), as defined by KDIGO criteria, was present at admission in 73.3% of cases, and among these, 69.7% required hemodialysis during hospitalization. Patients with AKI at admission exhibited higher serum levels of Ang-2 (2.9 [1.3, 8.3] vs. 0.7 [0.5, 3.1] ng/ml, p = 0.034), while no significant difference was observed in serum levels of von Willebrand factor (25.3 [3.1, 44.2] vs. 25.2 [3.5, 34.5] ng/ml, p >0.9). In multivariate analysis, serum level of von Willebrand factor (vWF) was independently associated with the need for hemodialysis during hospitalization (OR = 1.01, 95% CI: 1.00 – 1.02, p = 0.003). Conclusion Elevated serum von Willebrand Factor levels were independently associated with the requirement for hemodialysis in patients with severe leptospirosis. These findings suggest that vWF may serve as a potential biomarker for early risk stratification and prognosis in leptospirosis-associated AKI and may contribute to the understanding of AKI pathophysiology in these patients.

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