Unexplained inflammation in end-stage kidney disease: Is the combination of enhanced gastrointestinal permeability and reticuloendothelial dysfunction its cause?

Unexplained chronic inflammation is prevalent in end-stage kidney disease, and contributes toward accelerated cardiovascular disease, and premature death. The source of inflammation is unclear, although increased gastrointestinal permeability is a likely contributory factor. Whether a "leaky" gut leads to penetration of the systemic circulation by gut-derived pathogens is at least partly dependent on Kupffer cell function. These resident liver macrophages are an important part of the reticuloendothelial system (RES), and there is evidence for Kupffer cell and reticuloendothelial dysfunction in chronic kidney disease. These observations are compatible with the inflammatory milieu of chronic kidney disease being of gut origin. Measuring gut permeability in chronic kidney disease is challenging. Use of fecal biomarkers and other novel serum biomarkers represent potential alternative tools. One such marker is (1-3)-Beta-D-glucan, a polysaccharide constituent of many fungal, bacterial, and plant cell walls; levels of (1-3)-Beta-D-glucan are elevated in hemodialysis patients. Gastrointestinal permeability and impaired removal by the RES may contribute to these high levels, suggesting potential importance as a biomarker. High levels of (1-3)-Beta-D-glucan also falsely elevate endotoxin measurements. Measuring the contribution of gastrointestinal permeability and RES dysfunction to systemic inflammation may be an important step in designing therapies to reduce systemic inflammation in chronic kidney disease.