Analysis of the exacerbation mechanism of chronic kidney disease (CKD) cardiomyopathy through abnormal intestinal IgA secretion via vitamin A accumulation

<p>Introduction: Chronic kidney disease (CKD) poses a significant risk to cardiovascular health and life expectancy. Uremic substances such as indoxyl sulfate (IS) are implicated in this complication, being elevated in CKD patients due to intestinal dysbiosis and resistant to hemodialysis¹. Previous research has highlighted the role of vitamin A (VA) accumulation in increased uremic substance production, yet the precise mechanism remains elusive. This study aims to explore role of VA in immune maturation and investigate the mechanism behind enhanced production of intestinal bacteria-derived uremic substances.</p><p>Method: CKD mice (5/6 Nephrectomy: 5/6Nx) were established by removing 5/6ths of the kidneys from ICR mice and raised for 8 weeks. A sham group served as a control for comparison.</p><p>Results: VA-free feeding prevented abnormal immunoglobulin A (IgA) secretion and accumulation of uremic substances, including IS, in 5/6Nx mice, indicating VA accumulation disrupts intestinal immunity. Analysis of intestinal IgA-producing cells revealed increased retinoic acid secretion by dendritic cells in Peyer's patches of 5/6Nx mice, promoting germinal center reactions and IgA-producing cell differentiation. Inhibitors targeting this pathway reduced IgA secretion in the intestinal tract and accumulation of IS and other substances in 5/6Nx mice. This study unveils a novel mechanism of the kidney-gut axis mediated by VA and IgA, with implications for the development of therapeutic interventions.</p><p>Reference: 1. Fukuoka K, et al., Biochem Biophys Res Commun. 2023.</p>