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Research
Isaac Eliaz
Amitabha Medical Clinic and Healing Center
Corresponding Author
ORCiD: https://orcid.org/0000-0002-7935-2038
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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 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).
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 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).
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
Galectin-3, sepsis, acute kidney injury
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CURRENT STATUS: Published
View the published article at Critical Care.
Version 1
Posted 07 Jan, 2021
No community comments so far
Editorial decision: Major revision
On 18 Jan, 2021
Review #2 received
Received 12 Jan, 2021
Review #1 received
Received 10 Jan, 2021
Reviewer #2 agreed
On 01 Jan, 2021
Reviewer #1 agreed
On 01 Jan, 2021
Editor invited
On 29 Dec, 2020
Editor assigned
On 29 Dec, 2020
Reviewers invited
Invitations sent on 29 Dec, 2020
Submission checks complete
On 29 Dec, 2020
First submitted
On 27 Dec, 2020
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Subject Areas
Critical Care & Emergency Medicine
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A new preprint design is coming!
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See the published version of this preprint at Critical Care.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Isaac Eliaz
Amitabha Medical Clinic and Healing Center
Corresponding Author
ORCiD: https://orcid.org/0000-0002-7935-2038
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Critical Care.
Version 1
Posted 07 Jan, 2021
No community comments so far
Editorial decision: Major revision
On 18 Jan, 2021
Review #2 received
Received 12 Jan, 2021
Review #1 received
Received 10 Jan, 2021
Reviewer #2 agreed
On 01 Jan, 2021
Reviewer #1 agreed
On 01 Jan, 2021
Editor invited
On 29 Dec, 2020
Editor assigned
On 29 Dec, 2020
Reviewers invited
Invitations sent on 29 Dec, 2020
Submission checks complete
On 29 Dec, 2020
First submitted
On 27 Dec, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Critical Care & Emergency Medicine
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Critical Care.
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 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).
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 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).
Conclusions
This translational study demonstrates the importance of Gal-3 in the pathogenesis of S-AKI, and its potential utility as a therapeutic target.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
This is a list of supplementary files associated with this preprint. Click to download.
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