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

Crit Care. 2021 Mar 18;25(1):109. doi: 10.1186/s13054-021-03538-0.

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.

Keywords: Acute kidney injury; Galectin-3; Sepsis.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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