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. 2025 May 20:26:100226.
doi: 10.1016/j.toxcx.2025.100226. eCollection 2025 Jun.

Pathophysiological role of endothelial biomarkers in Bothrops sp. venom-induced renal dysfunction and the therapeutic effect of antivenom

Nicole Coelho Lopes  1 , Gdayllon Cavalcante Meneses  2 , Ranieri Sales de Souza Santos  1 , Leticia Machado de Araújo  2 , Bruna Viana Barroso Martins  2 , Katarina Maria Dos Reis Araújo  2 , Valéria Holanda Nogueira de Aquino  2 , Igor Moreira de Almeida  1 , Sandra Mara Brasileiro Mota  3 , Geraldo Bezerra da Silva Junior  4 , Camila Eleuterio Rodrigues  5   6 , Elizabeth De Francesco Daher  7 , Polianna Lemos Moura Moreira Albuquerque  8 , Alice Maria Costa Martins  1   2
Affiliations

Pathophysiological role of endothelial biomarkers in Bothrops sp. venom-induced renal dysfunction and the therapeutic effect of antivenom

Nicole Coelho Lopes et al. Toxicon X. .

Abstract

Snakebite antivenom (SAV) is the standard treatment option to neutralize the toxic effects of snake venom, but their consequences on kidney function need to be better understood. This study aims to evaluate the effects of antivenom on kidney and endothelial biomarkers due to Bothrops venom in two subgroups of patients distinguished by the presence of hemorrhagic syndrome at admission. This prospective study included 34 snakebite patients admitted to a tertiary hospital in Northeast Brazil between August 2019 and November 2020, 50 % of whom experienced spontaneous bleeding. Endothelial and kidney damage biomarkers were analyzed at three time points: before antivenom infusion and after 10 h and 20 h of antivenom infusion. Bleeding patients exhibited higher urine Neutrophil Gelatinase-Associated Lipocalin (uNGAL) and Kidney Injury Molecule-1 (KIM-1) levels, indicating incomplete renal recovery until 20h after antivenom. This group showed higher serum angiopoietin-2 (Ang-2) levels and vascular cell adhesion molecule-1 (VCAM-1). VCAM-1 levels positively correlated with kidney biomarker levels at each time point, especially after SAV. uNGAL was variant across VCAM-1, Ang-1, and Ang-2 levels before antivenom. Elevated levels of uNGAL and KIM-1, observed 10 h after SAV administration, may indicate incomplete renal protection and a potential risk for the development of chronic kidney injury, requiring future follow-up.

Keywords: Angiopoietins; Antivenom; KIM-1; Kidney injury; Snakebite; Vascular cell adhesion molecule-1.

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Conflict of interest statement

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Nicole Coelho Lopes reports financial support was provided by Foundation for Scientific and Technological Development and Support of Ceará. Ranieri Sales de Souza Santos reports financial support was provided by 10.13039/501100003593National Council for Scientific and Technological Development. Geraldo Bezerra da Silva reports a relationship with 10.13039/501100003593National Council for Scientific and Technological Development that includes: funding grants. Elizabeth De Francesco Daher reports a relationship with 10.13039/501100003593National Council for Scientific and Technological Development that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
Study flowchart.
Fig. 2
Fig. 2
Trajectories of kidney functional and damage biomarkers over the three-time points assessed by spontaneous bleeding status at hospital admission. (a) Serum creatinine; (b) uKIM-1/uCr; (c) uNGAL/uCr; (d) serum NGAL; (e) uMCP-1/uCr. Graphs depict least squares means and confidence limits, and variables were log-transformed when residuals were not normally distributed in each model.
Fig. 3
Fig. 3
Trajectories of endothelial biomarkers were assessed over the three time points by spontaneous bleeding status at hospital admission. (a) VCAM-1; (b) Ang-2; (c) Ang-1; (d) Ang-2/Ang-1 ratio; (e) Syndecan-1. Graphs depict least squares means and confidence limits, and variables were log-transformed when residuals were not normally distributed in each model.
Fig. 4
Fig. 4
Correlation between VCAM-1 and kidney damage biomarkers at each time point. (a) VCAM-1 vs. uNGAL/uCr before antivenom treatment; (b) VCAM-1 vs. uNGAL/uCr 10h after antivenom treatment; (c) VCAM-1 vs uNGAL/uCr 20h after antivenom treatment; (d) VCAM-1 vs uKIM-1/uCr before antivenom treatment; (e) VCAM-1 vs uKIM-1/uCr 10h after antivenom treatment; F. VCAM-1 vs uKIM-1/uCr 20h after antivenom treatment.
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