Efficacy and tolerability of sevelamer carbonate in hyperphosphatemic patients who have chronic kidney disease and are not on dialysis.
ABSTRACT Sevelamer carbonate is an improved, buffered form of sevelamer hydrochloride developed for the treatment of hyperphosphatemia in patients with chronic kidney disease. This study investigated the ability of sevelamer carbonate to control serum phosphorous in hyperphosphatemic patients who had chronic kidney disease and were not on dialysis.
This was an open-label, dosage-titration study. Patients with serum phosphorus > or =5.5 mg/dl were enrolled (n = 46). Sevelamer carbonate was administered for 8 wk. Patients were supplemented with native vitamin D (400 IU). The primary efficacy parameter was the change from baseline in serum phosphorous. Secondary measures included the percentage of serum phosphorus responders; changes in serum lipids, calcium-phosphorus product, and bicarbonate; and safety and tolerability.
Sevelamer carbonate treatment resulted in a statistically significant decrease in mean serum phosphorous levels from baseline to end of treatment. A total of 75% of patients with stage 4 and 70% of patients with stage 5 chronic kidney disease achieved the target serum phosphorous at the end of treatment. There were statistically significant decreases in serum calcium-phosphorus product and total and low-density lipoprotein cholesterol at the end of treatment and a statistically significant increase in mean serum bicarbonate levels (from 16.6 to 18.2 mEq/L). Sevelamer carbonate was well tolerated.
Sevelamer carbonate is an effective and well-tolerated therapy for the control of phosphorous levels in hyperphosphatemic patients who have chronic kidney disease and are not on dialysis.
SourceAvailable from: Sandeep K Mallipattu[Show abstract] [Hide abstract]
ABSTRACT: Purpose of review The critical role of advanced glycation end products (AGEs) in the progression of chronic diseases and their complications has recently become more apparent. This review summarizes the recent contributions to the field of AGEs in chronic kidney disease (CKD). Recent findings Over the past 3 decades, AGEs have been implicated in the progression of CKD, and specifically diabetic nephropathy. Although numerous in-vitro and in-vivo studies highlight the detrimental role of AGEs accumulation in tissue injury, few prospective human studies or clinical trials show that inhibiting this process ameliorates disease. Nonetheless, recent studies have focused on the novel mechanisms that contribute to end-organ injury as a result of AGEs accumulation, as well as novel targets of therapy in kidney disease. Summary As the prevalence and the incidence of CKD rises in the United States, it is essential to identify therapeutic strategies that either delay the progression of CKD or improve mortality in this population. The focus of this review is on highlighting the recent studies that advance our current understanding of the mechanisms mediating AGEs-induced CKD progression, as well as novel treatment strategies that have the potential to abrogate this disease process.Current Opinion in Nephrology and Hypertension 08/2014; 23(6). DOI:10.1097/MNH.0000000000000062 · 4.24 Impact Factor
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ABSTRACT: Hyperphosphatemia is one of the main risk factors contributing to morbidity and mortality in patients with end stage renal disease. The demand for a new phosphate binder is continuously increasing since the number of patients suffering under hyperphosphatemia is growing. However, side effects and high pill burden of currently available phosphate binders are the main reasons for low compliance and uncontrolled serum phosphate levels. Therefore, the aim of this study was to develop a novel phosphate binder with a high phosphate binding capacity over the entire gastrointestinal (GI) pH range. This novel phosphate binder C-PAM-10 is based on d-mannose coated nanocrystalline maghemite and belongs to the new class of phosphate binders, called the "iron based agents". It was possible to obtain a phosphate binding product that showed very high phosphate binding capacities with the characteristic of being pH independent at relevant pH ranges. The simulation of a GI passage ranging from pH 1.2 to pH 7.5 showed a 2.5 times higher phosphate binding capacity compared to the commonly used phosphate binder sevelamer carbonate. The simulation of a pH sensitive coating that releases the iron based phosphate binder at pH values ≥4.5 still showed a very high phosphate binding capacity combined with very low iron release which might decrease iron related side effects in vivo. Therefore, C-PAM-10 and its variations may be very promising candidates as a superior phosphate binder. Copyright © 2014 Elsevier B.V. All rights reserved.International Journal of Pharmaceutics 11/2014; 482(1-2). DOI:10.1016/j.ijpharm.2014.11.007 · 3.79 Impact Factor
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ABSTRACT: The primary goals were to re-examine whether sevelamer carbonate (SC) reduces advanced glycation end products (AGEs) (methylglyoxal and carboxymethyllysine [CML]), increases antioxidant defenses, reduces pro-oxidants, and improves hemoglobin A1c (HbA1c) in patients with type 2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD). Secondary goals examined albuminuria, age, race, sex, and metformin prescription. This two-center, randomized, intention-to-treat, open-label study evaluated 117 patients with T2DM (HbA1c >6.5%) and stages 2-4 DKD (urinary albumin/creatinine ratio ≥200 mg/g) treated with SC (1600 mg) or calcium carbonate (1200 mg), three times a day, without changing medications or diet. Statistical analyses used linear mixed models adjusted for randomization levels. Preselected subgroup analyses of sex, race, age, and metformin were conducted. SC lowered serum methylglyoxal (95% confidence interval [CI], -0.72 to -0.29; P<0.001), serum CML (95% CI, -5.08 to -1.35; P≤0.001), and intracellular CML (95% CI, -1.63 to -0.28; P=0.01). SC increased anti-inflammatory defenses, including nuclear factor like-2 (95% CI, 0.58 to 1.29; P=0.001), AGE receptor 1 (95% CI, 0.23 to 0.96; P=0.001), NAD-dependent deacetylase sirtuin-1 (95% CI, 0.20 to 0.86; P=0.002), and estrogen receptor α (95% CI, 1.38 to 2.73; P ≤0.001). SC also decreased proinflammatory factors such as TNF receptor 1 (95% CI, -1.56 to -0.72; P≤0.001) and the receptor for AGEs (95% CI, -0.58 to 1.53; P≤0.001). There were no differences in HbA1c, GFR, or albuminuria in the overall group. Subanalyses showed that SC lowered HbA1c in women (95% CI, -1.71 to -0.27; P=0.01, interaction P=0.002), and reduced albuminuria in those aged <65 years (95% CI, -1.15 to -0.07; P=0.03, interaction P=0.02) and non-Caucasians (95% CI, -1.11 to -0.22; P=0.003, interaction P≤0.001), whereas albuminuria increased after SC and calcium carbonate in Caucasians. SC reduced circulating and cellular AGEs, increased antioxidants, and decreased pro-oxidants, but did not change HbA1c or the albumin/creatinine ratio overall in patients with T2DM and DKD. Because subanalyses revealed that SC may reduce HbA1c and albuminuria in some patients with T2DM with DKD, further studies may be warranted. Copyright © 2015 by the American Society of Nephrology.Clinical Journal of the American Society of Nephrology 02/2015; 10(5). DOI:10.2215/CJN.07750814 · 5.25 Impact Factor