Endotoxin-binding affinity of sevelamer: a potential novel anti-inflammatory mechanism

Chronic inflammation is highly prevalent in patients with chronic kidney disease (CKD), and is associated with increased cardiovascular morbidity and mortality. There are numerous causes of inflammation in CKD, including the potential exposure to bacterial lipopolysaccharide (LPS) in the bloodstream from the intestinal tract as a result of uremia-related increases in intestinal permeability. Sevelamer, a commonly prescribed non-calcium, non-metal-based phosphate binder in CKD, also possesses putative anti-inflammatory properties, as its use has been associated with a reduction in systemic markers of inflammation. Emerging studies have provided direct evidence that sevelamer shows in vitro LPS-binding properties. Indirect clinical evidence suggests that sevelamer might also limit translocation of LPS from the intestinal lumen into the bloodstream. This review focuses on bacterial LPS as a source of chronic inflammation in CKD, and proposes that sevelamer might possess novel anti-inflammatory properties as a result of LPS binding in the intestinal tract. The proposed hypothesis that intestinal LPS-binding by sevelamer may lower circulating LPS, and in turn systemic inflammation, requires further evaluation in a clinical trial.