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bioRxiv · 10.1101/2025.08.01.668075

Renal and endothelial biomarkers in Chagas disease in the Brazilian Amazon region: early indicators of kidney injury and disease progression

Brandao, A. R. J.·Guerra, J. A. d. O.·Ortiz, J. V.·Sousa, D. R. T. d.·Alencar, G. M.·Derze, N. K. M.·Queiroz, J. V. C. d.·Brandao, J. B. S.·Silva, L. I. O. d.·Araujo, C. C. d. O.·Justiniano, S. C. B.·Silva, L. P. R. d.·Moctezuma-Guevara, E. I.·Smith-Doria, S.·Petruccelli, K. C. S.·Silva, P. R. L. d.·Silva, M. R. H. d. S. e.·Couceiro, K. d. N.·Meneses, G. C.·Araujo, L. M. d.·Daher, E. d. F.·Martins, A. M. C.·Ferreira, J. M. B. B.·Silva Junior, G. B. d.·Guerra, M. d. G. V. B.
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Abstract

Chagas disease (CD) is a significant public health problem in the Amazon, where the acute phase and oral transmission--often via contaminated acai--are predominant. These peculiarities influence clinical severity and immunological responses, highlighting the need to investigate non-traditional biomarkers for early detection of renal and endothelial dysfunctions, since conventional methods show limitations in identifying subclinical renal injury. To investigate the expression and clinical relevance of non-traditional biomarkers of renal injury and endothelial activation in acute and chronic CD in the Brazilian Amazon. A cross-sectional study was conducted between July 2021 and July 2023 at the Fundacao de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD), Manaus, Amazonas. Seventy-eight native Amazonian patients diagnosed with CD were evaluated and grouped by disease clinical phase: G1a (acute pre-treatment), G1b (acute post-treatment), G2a (chronic indeterminate), and G2b (chronic cardiac). Blood and urine levels of SYN-1, ANG-2, MCP-1, and NGAL were quantified using ELISA and correlated with traditional markers; including creatinine, urea, proteinuria, and glomerular filtration rate (GFR). Biomarkers were elevated across CD phases, despite traditional renal function parameters remaining within normal ranges. Urinary MCP-1 was significantly increased in the acute pre-treatment phase, reflecting early renal inflammation. SYN-1 was elevated in the acute and chronic indeterminate phases, indicating early endothelial activation. NGAL was increased in the chronic indeterminate group and ANG-2 in the chronic phase, suggesting progressive endothelial dysfunction. Traditional markers did not correlate with the biomarkers, suggesting their sensitivity in detecting early subclinical injury. This study highlights the importance of using these biomarkers for early diagnosis and monitoring of CD in the Amazon region. The elevated levels of SYN-1, ANG-2, MCP-1, and NGAL reveal early renal and endothelial dysfunction in CD patients undetectable by conventional tests. Incorporating these biomarkers into routine monitoring could support earlier therapeutic interventions and reduce associated renal and cardiovascular complications. AUTHOR SUMMARYChagas disease (CD) is a serious problem in Amazon, where many people get infected by eating contaminated food. If untreated, the disease can silently damage the kidneys and blood vessels. Standard medical tests often miss early signs of the damage, making it hard to intervene before the complications develop. This study aimed to investigate special markers in blood and urine that can indicate early kidney and blood vessel damage in patients at different stages of the disease in the Brazilian Amazon. We discovered that even though standard tests appeared normal, these proposed markers showed signs of damage. MCP-1 was high in early infection, suggesting kidney inflammation; SYN-1 and NGAL were elevated in later stages, suggesting ongoing damage and ANG-2 (linked to blood vessel problems) increased in chronic cases, that could indicate disease progression. In remote areas like the Amazon, where healthcare access is limited, early detection is crucial. The markers described in this study could help doctors detect early, treat and prevent complications like severe kidney and heart damage.

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Brandao, A. R. J., Guerra, J. A. d. O., Ortiz, J. V., Sousa, D. R. T. d., Alencar, G. M., Derze, N. K. M., Queiroz, J. V. C. d., Brandao, J. B. S., Silva, L. I. O. d., Araujo, C. C. d. O., Justiniano, S. C. B., Silva, L. P. R. d., Moctezuma-Guevara, E. I., Smith-Doria, S., Petruccelli, K. C. S., Silva, P. R. L. d., Silva, M. R. H. d. S. e., Couceiro, K. d. N., Meneses, G. C., Araujo, L. M. d., Daher, E. d. F., Martins, A. M. C., Ferreira, J. M. B. B., Silva Junior, G. B. d., Guerra, M. d. G. V. B.. 2025-08-04. Renal and endothelial biomarkers in Chagas disease in the Brazilian Amazon region: early indicators of kidney injury and disease progression. https://doi.org/10.1101/2025.08.01.668075

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