Evaluation of Potential Gastrointestinal Biomarker on the Outcome of Peritoneal Dialysis Patients

The human gut harbors ＞ 100 trillion microbial cells, which influence the nutrition, metabolism, physiology, and immune function of the host. Recent studies have highlighted the close relationship between the kidney and the gastrointestinal tract frequently referred to as the kidney-gut axis-in patients with chronic kidney disease (CKD). Uremia increases intestinal permeability, both in uremic rats and in patients with CKD. The disruption of colonic epithelial tight junction could subsequently lead to translocation of bacteria and endotoxin across the intestinal wall. Gut microbiome dysbiosis is associated with bacterial translocation, thereby contributing to microinflammation in patients with end stage renal disease. Endotoxin circulates in the plasma of healthy humans at low concentrations (up to 200 pg/ml). Recent evidence indicates that subclinical endotoxemia is a potential cause for inflammation in patients with CKD. Calprotectin is a 24 kilodalton calcium and zinc-binding protein, released by leukocytes at the site of inflammation. It can be detected in the feces where it remains stable for up to seven days. Increased fecal calprotectin levels are found in different inflammatory conditions, mainly the inflammatory bowel diseases. The relationship between fecal calprotectin and clinical outcome in peritoneal dialysis (PD) patient has not been explored. Protein fermentation by gut microbiota results in the generation of different metabolites, including phenols and indoles. Concentrations of indoxyl sulfate and p-cresyl sulfate in the serum are negatively correlated with the level of kidney function. An elevated level of indoxyl sulfate is associated with vascular stiffness, aortic calcification, and higher cardiovascular mortality. Free serum levels of p-cresol is associated with mortality in hemodialysis patients. Gut-derived uremic toxins contribute to progression of CKD as well as cardiovascular disease. Although the kidney-gut axis has been highlighted in patients with chronic kidney disease and end stage renal disease, little is known in the contribution of gastrointestinal biomarkers to systemic inflammation and clinical outcome of PD patients. The relationship among gastrointestinal biomarkers, intestinal microbiota and clinical outcome in PD patient has not been explored. This study seeks to provide insight into the following key questions: (1) To exam if the subclinical endotoxemia is a potential cause for inflammation in PD patients and to explore the role of peritoneal endotoxin on patient outcome (2) To explore if fecal calprotectin/cytokine could be a marker of intestinal inflammation in PD patients. (3) To explore a potential immunoregulatory role of the intestinal microbiota in PD patients.

Project ID:PC10703-0219
External Project ID:MOST106-2314-B182-032