Phosphate Binders and Nonphosphate Effects in the Gastrointestinal Tract

Abstract

Phosphate binders are commonly prescribed in patients with end-stage kidney disease (ESKD) to prevent and treat hyperphosphatemia. These binders are usually associated with gastrointestinal distress, may bind molecules other than phosphate, and may alter the gut microbiota, altogether having systemic effects unrelated to phosphate control. Sevelamer is the most studied of the available binders for non-phosphate-related effects including binding to bile acids, endotoxins, gut microbiota-derived metabolites, and advanced glycation end-products. Other binders (calciumand non-calcium-based binders) may bind vitamins, such as vitamin K and folic acid. Moreover, the relatively new iron-based phosphate binders may alter the gut microbiota as some of the iron or organic ligands may be utilized by the gastrointestinal bacteria. The objective of this narrative review is to provide the current evidence for the non-phosphate effects of phosphate binders on gastrointestinal function, nutrient and molecule binding, and the gut microbiome.

Comparative Gut Microbiome Differences between Ferric Citrate and Calcium Carbonate Phosphate Binders in Patients with End-Stage Kidney Disease

“…Iron-based phosphate binders had been proposed to alter the gut microbiota [ 24 ]. Limited evidence demonstrated calcium-based phosphate binders’ effect on the gut microbiota in the literature [ 24 ]. In our study, Bacteroidaceae , a typical and large family of gastrointestinal Gram-negative bacteria, was enriched in ferric citrate users.…”

“…The precision of dietary intake can benefit from having more objective dietary records. Third, other phosphate binders (e.g., lanthanum carbonate, sevelamer hydrochloride/carbonate, or sucroferric oxyhydroxide) that potentially affect gut microbiota were not evaluated in this study [ 24 , 53 , 54 ]. Fourth, the study was performed on Asian HD patients whose diet may be different from other populations.…”

Efficacy and Safety of a Novel Nicotinamide Modified-Release Formulation in the Treatment of Refractory Hyperphosphatemia in Patients Receiving Hemodialysis—A Randomized Clinical Trial

“…These effects include e.g. accumulation of metals in different organs, disturbances of the gut microbiome, and binding of important nutrients such as vitamin K and may adversely affect clinical outcomes [16].…”

“…These effects include, for example, accumulation of metals in different organs, disturbances of the gut microbiome, and binding of important nutrients such as vitamin K and may adversely affect clinical outcomes. 16 Therefore, therapy approaches that combine different modes of action may represent a reasonable alternative to improve phosphate control.…”

Phosphate, Microbiota and CKD

“…Sevelamer, the first non-metal-containing phosphate binder, launched in 2001, is a large cross-linked cationic polymer and non-absorbable anion exchange binder available as sevelamer carbonate or hydrochloride [ 25 ]. In addition to phosphate, sevelamer may bind endotoxins, gut microbiota-derived metabolites, advanced glycation end products and bile salts, consequently decreasing serum low-density lipoprotein (LDL) cholesterol and inflammatory markers in dialysis patients [ 25 , 35 , 36 , 37 , 38 ]. Of these, the most prominent effect is the reduction in LDL-cholesterol, to the point that this is used by clinicians to assess compliance.…”