# A Comprehensive Analysis of Renal and Endothelium Dysfunction Markers Fourteen Years after Hemorrhagic Fever with Renal Syndrome Contraction

**Authors:** Dragan Ledina, Ivo Ivić, Ante Tadin, Kristian Bodulić, James W. LeDuc, Alemka Markotić

PMC · DOI: 10.3390/life14050575 · 2024-04-30

## TL;DR

This study finds that people who had HFRS 14 years ago still show signs of kidney and blood vessel issues compared to healthy people.

## Contribution

The study is the first to investigate long-term renal and endothelial dysfunction in HFRS survivors.

## Key findings

- Convalescent HFRS patients had higher levels of inflammation and kidney damage markers compared to healthy individuals.
- 24-hour urine analysis showed lower sodium and potassium levels and higher proteinuria in HFRS patients.
- Only serum sVCAM-1 and urine VEGF showed a weak association with HFRS contraction.

## Abstract

While the pathology of acute hemorrhagic fever with renal syndrome (HFRS) has been widely researched, details on the chronic HFRS sequelae remain mainly unexplored. In this study, we analyzed the clinical and laboratory characteristics of 30 convalescent HFRS patients 14 years after the disease contraction, mainly emphasizing several endothelial dysfunction parameters. Convalescent HFRS patients exhibited significantly higher serum levels of erythrocyte sedimentation rate, von Willebrand factor, uric acid, C-reactive protein and immunoglobulin A when compared to healthy individuals. Furthermore, 24 h urine analyses revealed significantly lower sodium and potassium urine levels, as well as significantly higher proteinuria, microalbumin levels and β2-microglobulin levels when compared to healthy individuals. First morning urine analysis revealed significantly higher levels of hematuria in convalescent HFRS patients. None of the additional analyzed endothelium dysfunction markers were significantly different in post-HFRS patients and healthy individuals, including serum and urine P-selectin, E-selectin, soluble intercellular adhesion molecule 1, vascular intercellular adhesion molecule 1 (sVCAM-1) and vascular endothelial growth factor (VEGF). However, binary logistic regression revealed a weak association of serum sVCAM-1 and urine VEGF levels with HFRS contraction. Generally, our findings suggest mild chronic inflammation and renal dysfunction levels in convalescent HFRS patients 14 years after the disease contraction.

## Linked entities

- **Proteins:** SELP (selectin P), Sele (selectin, endothelial cell)
- **Chemicals:** uric acid (PubChem CID 1175), sodium (PubChem CID 5360545), potassium (PubChem CID 813)

## Full-text entities

- **Genes:** VWF (von Willebrand factor) [NCBI Gene 7450] {aka F8VWF, VWD}, SELE (selectin E) [NCBI Gene 6401] {aka CD62E, ELAM, ELAM1, ESEL, LECAM2, selectin-e}, HLA-G (major histocompatibility complex, class I, G) [NCBI Gene 3135] {aka MHC-G}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, SELP (selectin P) [NCBI Gene 6403] {aka CD62, CD62P, GMP140, GRMP, LECAM3, PADGEM}
- **Diseases:** chronic inflammation (MESH:D007249), proteinuria (MESH:D011507), HFRS (MESH:D006480), endothelial dysfunction (MESH:D014652), endothelium dysfunction (MESH:D006331), Renal and Endothelium Dysfunction (MESH:D007674), hematuria (MESH:D006417)
- **Chemicals:** uric acid (MESH:D014527), potassium (MESH:D011188), sodium (MESH:D012964)
- **Species:** Homo sapiens (human, species) [taxon 9606]

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Source: https://tomesphere.com/paper/PMC11122023