Does the Administration of Sevelamer or Nicotinamide Modify Uremic Toxins or Endotoxemia in Chronic Hemodialysis Patients?

Background Hyperphosphatemia control is a major issue in hemodialysis patients. Both sevelamer and nicotinamide are prescribed for this purpose. In addition, they exert pleiotropic effects such as an improvement of inflammatory status and potentially enhanced clearance of uremic toxins. In the present secondary analysis of the NICOREN trial, we investigated the impact of sevelamer and nicotinamide on uremic toxins, toxin precursors, and endotoxemia in chronic hemodialysis patients. Methods Circulating uremic toxins (including phenylacetylglutamine, trimethylamine-N-oxide, p-cresyl sulfate, indoxyl sulfate, kynurenine, hippuric acid, indole-3-acetic acid, 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid, kynurenic acid, and p-cresyl glucuronide) and precursors were measured by ultra-performance liquid chromatography-tandem mass spectrometry, and urea, uric acid, phosphate, C-reactive protein, and intact parathyroid hormone by routine biochemistry methods. Serum endotoxin (evaluated by lipopolysaccharide levels) and C-terminal fibroblast growth factor-23 levels were measured using enzyme-linked immunosorbent assay kits. Results One hundred hemodialysis patients were randomized to receive either nicotinamide or sevelamer treatment. Among them, 63% were male, mean (± standard deviation) age was 65 ± 14 years, 47% had diabetes mellitus, and 51% had a history of cardiovascular disease. In the sevelamer group, but not the nicotinamide group, serum levels of urea, uric acid, and fibroblast growth factor-23 were significantly reduced after 6 months of treatment. The other circulating uremic toxins and toxin precursors remained unchanged in response to either phosphate-lowering agent. Sevelamer treatment led to a marked decrease in serum lipopolysaccharide ( p