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

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.

• Authors: Haibing Sun, Huiping Jiang, Amity Eliaz, John A Kellum, Zhiyong Peng, Isaac Eliaz
• Journal: Critical care (London, England) (Crit Care) Vol. 25 Issue 1 Pg. 109 (03 18 2021) ISSN: 1466-609X [Electronic] England
• PMID: 33736691 (Publication Type: Journal Article, Observational Study, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Proteins
• Galectin 3
• Galectins
• Il6 protein, rat
• Interleukin-6
• LGALS3 protein, human
• Lgals3 protein, rat
• Creatinine

Topics

• APACHE
• Acute Kidney Injury (blood, etiology)
• Aged
• Animals
• Blood Proteins (analysis)
• Cecum (abnormalities)
• Chi-Square Distribution
• China
• Creatinine (analysis, blood)
• Disease Models, Animal
• Female
• Galectin 3 (analysis, blood)
• Galectins (analysis, blood)
• Humans
• Intensive Care Units (organization & administration, statistics & numerical data)
• Interleukin-6 (analysis, blood)
• Ligation (adverse effects, methods)
• Logistic Models
• Male
• Middle Aged
• Prospective Studies
• Rats
• Rats, Sprague-Dawley (injuries, surgery)
• Sepsis (blood, complications)
• Survival Analysis