Protein-Bound Uremic Toxins Lowering Effect of Sevelamer in Pre-Dialysis Chronic Kidney Disease Patients with Hyperphosphatemia: A Randomized Controlled Trial.

Kearkiat Praditpornsilpa,Paweena Susantitaphong,Jeerath Phannajit,Kullaya Takkavatakarn,Asada Leelahavanichkul,Somchai Eiam-Ong,Warumphon Sukkumme,Pajaree Chariyavilaskul,Pisut Katavetin,Pongpratch Puapatanakul,Patita Sitticharoenchai

doi:10.3390/toxins13100688

Abstract

P-cresyl sulfate and indoxyl sulfate are strongly associated with cardiovascular events and all-cause mortality in chronic kidney disease (CKD). This randomized controlled trial was conducted to compare the effects between sevelamer and calcium carbonate on protein-bound uremic toxins in pre-dialysis CKD patients with hyperphosphatemia. Forty pre-dialysis CKD patients with persistent hyperphosphatemia were randomly assigned to receive either 2400 mg of sevelamer daily or 1500 mg of calcium carbonate daily for 24 weeks. A significant decrease of total serum p-cresyl sulfate was observed in sevelamer therapy compared to calcium carbonate therapy (mean difference between two groups −5.61 mg/L; 95% CI −11.01 to −0.27 mg/L; p = 0.04). There was no significant difference in serum indoxyl sulfate levels (p = 0.36). Sevelamer had effects in terms of lowering fibroblast growth factor 23 (p = 0.01) and low-density lipoprotein cholesterol levels (p = 0.04). Sevelamer showed benefits in terms of retarding CKD progression. Changes in vascular stiffness were not found in this study.

Highlights

Chronic kidney disease (CKD) is one of the most important global health problems, and it significantly increases cardiovascular risk and mortality [1]
Among 250 pre-dialysis CKD patients in the outpatient department, 48 patients were eligible for inclusion in this trial
The higher number of pathogenic microbes and the increased intestinal permeability of CKD patients contribute to the elevation of gut-derived uremic toxins such as p-cresyl sulfate and indoxyl sulfate [15]

Summary

Introduction

Chronic kidney disease (CKD) is one of the most important global health problems, and it significantly increases cardiovascular risk and mortality [1]. Several risk factors for CKD have been proposed, including traditional risk factors, such as diabetes, hypertension, and dyslipidemia, and uremia-related risk factors including anemia, mineral and bone disorders, inflammation, oxidative stress, and uremic toxins [2]. In stage 4–5 CKD, adaptation is no longer adequate, and hyperphosphatemia develops despite high FGF23 levels [3]. Several experimental and epidemiological studies in CKD have illustrated correlations between high FGF23 levels and various deleterious effects, including left ventricular hypertrophy [4], vascular calcification [5], impaired immune system, anemia, and decreased bone mineralization [6]

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Results

Conclusion