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Published in: Critical Care 1/2021

Open Access 01-12-2021 | Acute Kidney Injury | Research

Galectin-3 in septic acute kidney injury: a translational study

Authors: Haibing Sun, Huiping Jiang, Amity Eliaz, John A. Kellum, Zhiyong Peng, Isaac Eliaz

Published in: Critical Care | Issue 1/2021

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Abstract

Background

Galectin-3 (Gal-3) is a pleiotropic glycan-binding protein shown to be involved in sepsis and acute kidney injury (AKI). However, its role has never been elucidated in sepsis-associated AKI (S-AKI). We aimed to explore Gal-3’s role and its potential utility as a therapeutic target in S-AKI.

Methods

In 57 patients admitted to the intensive care unit (ICU) with sepsis, serum Gal-3 was examined as a predictor of ICU mortality and development of AKI. In a rat model of S-AKI induced by cecal ligation and puncture (CLP), 7-day mortality and serum Gal-3, Interleukin-6 (IL-6), and creatinine were examined at 2, 8, and 24 hours (h) post-CLP. Two experimental groups received the Gal-3 inhibitor modified citrus pectin (P-MCP) at 400 mg/kg/day and 1200 mg/kg/day, while the control group received water only (n = 18 in each group).

Results

Among 57 patients, 27 developed AKI and 8 died in the ICU. Serum Gal-3 was an independent predictor of AKI (OR = 1.2 [95% CI 1.1–1.4], p = 0.01) and ICU mortality (OR = 1.4 [95% CI 1.1–2.2], p = 0.04) before and after controlling for age, AKI, and acute physiology and chronic health evaluation (APACHE II) score. In the CLP rat experiment, serum Gal-3 peaked earlier than IL-6. Serum Gal-3 was significantly lower in both P-MCP groups compared to control at 2 h post-CLP (400 mg: p = 0.003; 1200 mg: p = 0.002), and IL-6 was significantly lower in both P-MCP groups at all time points with a maximum difference at 24 h post-CLP (400 mg: p = 0.015; 1200 mg: p = 0.02). In the Gal-3 inhibitor groups, 7-day mortality was significantly reduced from 61% in the control group to 28% (400 mg P-MCP: p = 0.03) and 22% (1200 mg P-MCP: p = 0.001). Rates of AKI per RIFLE criteria were significantly reduced from 89% in the control group to 44% in both P-MCP groups (400 mg: p = 0.007; 1200 mg: p = 0.007).

Conclusions

This translational study demonstrates the importance of Gal-3 in the pathogenesis of S-AKI, and its potential utility as a therapeutic target.

Graphic abstract

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Metadata
Title
Galectin-3 in septic acute kidney injury: a translational study
Authors
Haibing Sun
Huiping Jiang
Amity Eliaz
John A. Kellum
Zhiyong Peng
Isaac Eliaz
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2021
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-021-03538-0

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