High salt exacerbates acute kidney injury by disturbing the activation of CD5L/apoptosis inhibitor of macrophage (AIM) protein

• Published in: PloS one Vol. 16; no. 11; p. e0260449
• Main Authors: Wang, Ching-Ting, Tezuka, Tetsushi, Takeda, Naoki, Araki, Kimi, Arai, Satoko, Miyazaki, Toru
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 29-11-2021; Public Library of Science (PLoS)
• Subjects: Acute Kidney Injury - metabolism; Acute Kidney Injury - pathology; Acute renal failure; Animals; Antibodies; Apoptosis; Apoptosis Regulatory Proteins - metabolism; Biochemistry, Molecular Biology; Biology; Biology and Life Sciences; Biomarkers; Damage; Development and progression; Dissociation; Experiments; Female; Health aspects; Immune system; Immunoglobulin M; Inhibitors; Injection; Injuries; Integrative medicine; Ischemia; Kidney diseases; Kidney Tubules, Proximal - metabolism; Kidney Tubules, Proximal - pathology; Kidneys; Laboratory animals; Life Sciences; Macrophages; Medicine; Medicine and Health Sciences; Mice; Mice, Inbred ICR; Pathogenesis; Physical Sciences; Physiological aspects; Proteins; Reagents; Receptors, Scavenger - metabolism; Repair; Reperfusion; Research and Analysis Methods; Salt; Salts; Sodium Chloride, Dietary - adverse effects; Sodium Chloride, Dietary - metabolism; Sodium in the body; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0260449

The influence of excess salt intake on acute kidney injury (AKI) has not been examined precisely except for some clinical data, unlike in chronic kidney disease. Here, we addressed the influence of high salt (HS) on AKI and its underlying mechanisms in terms of the activity of circulating apoptosis inhibitor of macrophage (AIM, also called CD5L) protein, a facilitator of AKI repair. HS loading in mice subjected to ischemia/reperfusion (IR) resulted in high mortality with advanced renal tubular obstruction and marked exacerbation in biomarkers of proximal renal tubular damage. This AKI exacerbation appeared to be caused mainly by the reduced AIM dissociation from IgM pentamer in serum, as IgM-free AIM is indispensable for the removal of intratubular debris to facilitate AKI repair. Injection of recombinant AIM (rAIM) ameliorated the AKI induced by IR/HS, dramatically improving the tubular damage and mouse survival. The repair of lethal AKI by AIM was dependent on AIM/ kidney injury molecule-1 (KIM-1) axis, as rAIM injection was not effective in KIM-1 deficient mice. Our results demonstrate that the inhibition of AIM dissociation from IgM is an important reason for the exacerbation of AKI by HS, that AIM is a strong therapeutic tool for severe AKI.