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. MethodsIn 57 patients admitted to the intensive care unit (ICU) with sepsis, serum Gal-3 was examined as a predictor of ICU mortality and AKI. In a rat model of S-AKI induced by cecal ligation and puncture (CLP), 7-day mortality and serum Gal-3, IL-6, and creatinine were examined at baseline, 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). ResultsAmong 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 Interleukin-6 (IL-6). Serum Gal-3 was significantly lower in both P-MCP-treated 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-treated 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-treated groups (400mg: p = 0.007; 1200mg: p = 0.007). ConclusionsThis translational study demonstrates the importance of Gal-3 in the pathogenesis of S-AKI, and its potential utility as a therapeutic target.

The Role of Serum Galectin-3 Levels in Patients with Sarcoidosis

“…In vitro studies investigating galectin-3 have demonstrated that the absence of galectin-3 may improve fibrotic response in the kidneys, liver, and lungs [15,16]. Previous studies have also reported increased levels of galectin-3 in diseases progressing with fibrosis, such as cirrhosis and idiopathic pulmonary fibrosis [13][14][15][16][17]. A previous study reported that galectin-3 levels were elevated in sarcoidosis patients with cardiac involvement when compared to the controls [18].…”

“…Extracellular galectin-3 mediates inflammation and leukocyte adhesion and plays roles in the retrieval and activation of neutrophils (NEUs) [11] and also has a crucial role in the stimulation of inflammation in a wide range of acute and chronic events, particularly neurologic degeneration, autoimmune disorders, atherosclerosis and heart failure, and response to infections or diseases of the lungs, kidney, and liver [12]. A recent study by Sun et al [13] showed a relationship between galectin-3 level and prognosis of acute kidney injury. These observations suggest that galectin-3 may result in fibrosis in several systems.…”