# Endothelin-2 and Its Association with Uric Acid Levels and Systemic Inflammation: Relevance to Chronic Kidney Disease Progression

**Authors:** Alexander Bozhidarov Blazhev, Krasimir Kostov, Borislav Ivanov Ignatov, Tsvetelina Eftimova, Tatyana Nedkova Simeonova, Svetla Ognyanova Blazheva

PMC · DOI: 10.3390/ijms27010540 · International Journal of Molecular Sciences · 2026-01-05

## TL;DR

This study explores how endothelin-2 (ET-2) relates to inflammation and uric acid in chronic kidney disease (CKD) patients.

## Contribution

The study identifies ET-2 as a potential biomarker for CKD severity and metabolic inflammation.

## Key findings

- ET-2 levels were significantly higher in advanced CKD patients compared to healthy controls.
- ET-2 positively correlated with uric acid and inflammatory markers like hsCRP and IL-6.
- ET-1 and ET-3 levels did not show significant differences across CKD stages.

## Abstract

Chronic kidney disease (CKD) is associated with chronic inflammation and metabolic dysregulation. While endothelin-1 (ET-1) has been extensively studied, the role of endothelin-2 (ET-2) in CKD remains poorly understood. This cross-sectional study included 76 participants, 12 healthy controls and 64 CKD patients, stratified into three groups based on estimated glomerular filtration rate (eGFR): Group 1 (eGFR ≥ 90 mL/min/1.73 m2), Group 2 (eGFR 45–89 mL/min/1.73 m2), and Group 3 (eGFR 15–44 mL/min/1.73 m2). Serum concentrations of ET-1, ET-2, ET-3, uric acid (UA), and inflammatory markers (hsCRP and IL-6) were measured. ET-2 levels were significantly higher in the advanced CKD group (median 24.49 pg/mL) compared to controls (median 19.32 pg/mL; p = 0.030). No significant differences were observed for ET-1 or ET-3 across groups. ET-2 levels positively correlated with UA (rho = 0.243, p = 0.036), hsCRP (rho = 0.241, p = 0.039), and IL-6 (rho = 0.244, p = 0.038). These findings suggest that ET-2 may represent a potential biomarker reflecting metabolic and inflammatory dysregulation in CKD and highlight its possible relevance in disease severity assessment.

## Linked entities

- **Proteins:** EDN2 (endothelin 2), IL6 (interleukin 6)
- **Chemicals:** uric acid (PubChem CID 1175)
- **Diseases:** chronic kidney disease (MONDO:0005300)

## Full-text entities

- **Genes:** IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, EDN1 (endothelin 1) [NCBI Gene 1906] {aka ARCND3, ET1, HDLCQ7, PPET1, QME}, EDN3 (endothelin 3) [NCBI Gene 1908] {aka ET-3, ET3, HSCR4, PPET3, WS4B}, EDN2 (endothelin 2) [NCBI Gene 1907] {aka ET-2, ET2, PPET2}
- **Diseases:** CKD (MESH:D051436), chronic (MESH:D002908), Inflammation (MESH:D007249), metabolic dysregulation (MESH:D021081)
- **Chemicals:** UA (MESH:D014527)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12787035/full.md

## References

57 references — full list in the complete paper: https://tomesphere.com/paper/PMC12787035/full.md

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Source: https://tomesphere.com/paper/PMC12787035