Circulating Bacterial Fragments as Cardiovascular Risk Factors in CKD

Cardiovascular disease (CVD) is a major cause of mortality and morbidity in patients with CKD. In the past decade, intestinal dysbiosis and altered gut epithelial barrier function are increasingly recognized in CKD. Uremic patients have slow intestinal transit time, impaired protein assimilation, and decreased consumption of dietary fiber. The use of multiple medications also may contribute to the proliferation of dysbiotic bacteria, which affect the barrier function of intestinal epithelium. In addition, fluid overload and uremic toxins per se directly reduce the gut barrier function. The major consequence of these alterations, the translocation of bacterial fragments from bowel lumen to systemic circulation, can lead to diverse biologic effects and probably represents an important nontraditional CVD risk factor in CKD. Among all bacterial fragments, endotoxin is the most well studied. Plasma endotoxin levels are markedly elevated in both patients with CKD and those on dialysis, and are associated with the systemic inflammatory state, accelerated atherosclerosis, and clinical CVD in patients on dialysis. Optimization of BP control and the use of ultrapure dialysate can reduce plasma endotoxin levels, with probable metabolic and cardiovascular benefits. The benefit of synbiotic therapy is not confirmed, although results from animal studies are impressive. The biologic effects and clinical relevance of other bacterial fragments, such as bacterial DNA fragments, are less well defined. Further studies are needed to delineate the pathogenic relation between circulating bacterial fragments and CVD, and to define the role of the plasma bacterial fragment level as a prognostic indicator of CKD.