Effects of Sevelamer and Calcium-Based Phosphate Binders on Lipid and Inflammatory Markers in Hemodialysis Patients

Abstract

Introduction: Cardiovascular disease accounts for almost half of all deaths in individuals with chronic kidney disease stage 5 despite advances in both dialysis treatment and cardiology. A combination of lipid-lowering and anti-inflammatory effects along with avoidance of hypercalcemia should be taken into account when choosing phosphorus binders for maintenance hemodialysis (MHD) patients. Methods: We examined the association of sevelamer versus calcium-based phosphorus binders with lipid profile, inflammatory markers including C-reactive protein (CRP), and mineral metabolism in MHD patients who participated in the Nutritional and Inflammatory Evaluation of Dialysis Patients (NIED) study from October 2001 to July 2005. Results: Of the 787 MHD patients in the NIED study, 697 were on either sevelamer, a calcium-based binder, or both and eligible for this study. We compared the groups based on taking sevelamer monotherapy (n = 283) or calcium binder monotherapy (n = 266) for serum phosphate control. There were no differences between the groups on dialysis vintage. There were significant differences in age, serum calcium and phosphorus levels, as well as intact parathyroid hormone levels. Using a logistic regression models, the sevelamer group had a higher odds of serum CRP <10 mg/l [odds ratio (OR): 1.06, 95% CI: 1.02–1.11] and LDL cholesterol <70 mg/dl (OR: 1.33, 95% CI: 1.19–1.47) when compared to the calcium binder group independent of age, vintage, body mass index, statin use or other variables. Conclusion: The improvements in multiple surrogate markers of inflammation and lipids in the NIED study make sevelamer a promising therapy for treatment in MHD patients with high risk of cardiovascular disease and mortality.

Uremic Toxicity of Advanced Glycation End Products in CKD

“…Moreover, sevelamer decreases CML levels, oxidative stress, and inflammation and increases AGER1 expression. [150][151][152][153] The results of a randomized trial in patients on HD showed that sevelamer slows calcification and suppresses pentosidine accumulation. 154 Although longterm clinical studies in patients with CKD have not yet been performed, a short-term comparison of sevelamer with calcium carbonate showed that it lowered serum AGEs in patients on HD.…”

Association of Serum Alkaline Phosphatase with Coronary Artery Calcification in Maintenance Hemodialysis Patients

“…We studied a randomly selected group of MHD patients who participated in the substudy of the Nutritional and Inflammatory Evaluation in Dialysis (NIED) Study (see the NIED Study website at http:// www.NIEDStudy.org for more details, as well as previous publications [12][13][14][15]). The original patient cohort was derived from a pool of more than 3000 MHD outpatients during 5 yr in eight DaVita long-term dialysis facilities in the South Bay Los Angeles area.…”

Correlation Between Intestinal Colony Numbers and Inflammation Markers (TNF-Alpha, IL-6, High-Sensitive CRP) Following the Use of Sevelamer in Rats with Kidney Failure

“…18,19 In hemodialysis patients, it was determined that, with the use of sevelamer, CRP, LDL and total cholesterol levels further decreased in comparison to calcium-containing phosphorus binders. 20 In cases with ESKD with a very high cardiovascular mortality due to dyslipidemia and inflammation, the use of sevelamer has been a promising treatment method for improving hyperlipidemia and inflammation. 20 Similarly in our study, in rats with renal failure, inflammation markers increased (TNF-alpha, CRP, IL-10), but the use of sevelamer decreased these markers.…”

“…20 In cases with ESKD with a very high cardiovascular mortality due to dyslipidemia and inflammation, the use of sevelamer has been a promising treatment method for improving hyperlipidemia and inflammation. 20 Similarly in our study, in rats with renal failure, inflammation markers increased (TNF-alpha, CRP, IL-10), but the use of sevelamer decreased these markers.…”