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Endotoxin Binding by Sevelamer: Potential Impact on Nutritional Status

DOI: 10.1155/2013/954956

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Abstract:

Patients on hemodialysis (HD) have a high burden of chronic inflammation induced associated with multiple comorbidities including poor nutritional status. Endotoxin (ET) is a Gram-negative bacterial cell wall component and a potent stimulus for innate immune system activation leading to the transcription of proinflammatory cytokines (e.g., IL-1, IL-6, and TNFα) that adversely affect protein metabolism and nutrition. Several cross-sectional observational studies have found that elevated serum ET concentrations in hemodialysis patients are associated with lower serum albumin, higher proinflammatory cytokine, and C-reactive protein concentrations. Possible sources of ET in the systemic circulation are bacterial translocation from the gastrointestinal tract and iron supplementation, potentially leading to intestinal bacterial overgrowth. Sevelamer is a nonabsorbable hydrogel approved for use as a phosphate binder in HD patients. Reductions in serum ET concentrations in hemodialysis patients have been observed with sevelamer therapy in observational studies and the few published interventional studies. Reduction of ET concentrations was associated with concomitant reductions in TNFα, IL-6, and CRP and improvement in serum albumin in the majority of these small studies. Additional studies are needed to evaluate the potential effects of sevelamer treatment on nutritional status in chronic kidney disease (CKD) patients with elevated ET. 1. Introduction Proinflammatory cytokines such as IL-1, IL-6, and TNF- and the anti-inflammatory cytokine IL-10 are elevated in hemodialysis (HD) patients [1]. Several factors are linked with the Proinflammatory state in end-stage renal disease (ESRD) patients on dialysis including nutritional status, diabetes, hypertension, sepsis, and biocompatibility with dialysis membranes [1]. Poor nutritional status is a vexing clinical problem that occurs in up to 50% of ESRD patients on hemodialysis and is associated with increased mortality [2]. Documented appetite loss in ESRD patients is associated with higher mortality rates [3]. Albumin is a negative acute phase reactant, and low serum albumin concentrations are associated with elevated markers of inflammation including IL-6, CRP, and TNF- [4–6]. ESRD patients on HD exhibit increased protein catabolism profiles and greater skeletal muscle breakdown that is correlated with reduced serum albumin concentrations [5, 7, 8]. This loss of lean body mass in concert with chronic inflammation has been identified as a major risk factor for cardiac heart failure in ESRD patients [9, 10].

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