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The purpose of this study is to determine whether oral sevelamer carbonate binds advanced glycation end products (AGEs) in the gastrointestinal (GI) tract of patients with diabetic nephropathy leading to decrease body AGE load and therefore decreases the inflammation and oxidative stress in these patients.
Traditional vascular risk factors alone cannot account for the elevated cardiovascular risk in patients with chronic kidney disease (CKD). In addition to a high prevalence of hypertension and diabetes, patients with CKD have elevated levels of inflammatory markers and OS, which are emerging as important risk factors for cardiovascular disease (CVD). Patients with CKD are also known to have elevated levels of circulating advanced glycation end products (AGE's), which have been shown to induce OS and to play a central role in the development of diabetic microvascular and macrovascular complications. In CKD patients, AGE's accumulate secondary to decreased renal clearance and increased endogenous production in the setting of high levels of OS. Efforts to understand relationships between the multiple vascular risk factors in chronic kidney disease may lead to reduced morbidity and mortality in this population of patients.
Sevelamer Hydrochloride is an anion exchange resin composed of multiple positively charged amine groups indicated for the treatment of hyperphosphatemia in patients with stage V CKD. The positively charged amine groups bind negatively charged dietary phosphate preventing systemic absorption. Sevelamer Hydrochloride has been shown to have the added benefits of lowering LDL levels, lowering highly sensitive C-reactive protein (hsCRP) levels, and improving insulin resistance. Patients treated with Sevelamer Hydrochloride have also been shown to have improved vascular compliance and reduced progression of coronary vascular calcification. Since AGE's are mostly negatively charged compounds, Sevelamer Carbonate by analogy, may have anti-AGE effects which could reduce inflammation and oxidative stress. Sevelamer Carbonate would have a major advantage over Calcium Carbonate-based phosphate binders, based on the fact that it would have the added advantage of reducing the levels of AGEs. The resultant reduction of both OS and inflammation would be expected to have an independent beneficial effect on the rate of progression of CKD and CVD.
We have shown in CKD patients and in animal models that AGE's correlate with levels of OS, LDL, hsCRP, and insulin resistance. Additionally, these factors can be remediated in CKD and non-CKD diabetics by decreasing overall AGE load, particularly in the diet. To date, the effect of Sevelamer Hydrochloride or Sevelamer Carbonate on OS and circulating AGE levels has not been studied. The anti-inflammatory and lipid-lowering effects of Sevelamer Hydrochloride may occur through lowering serum AGE levels and OS. Sevelamer Carbonate is an improved form of Sevelamer Hydrochloride that has been shown to be a safe and effective alternative to calcium carbonate in the treatment of hyperphosphatemia in the earlier sta`ges of CKD without causing metabolic acidosis. The development of Sevelamer Carbonate provides an opportunity to study patients with earlier stages of CKD, and to determine if it prevents or slows the progression of CKD. We propose a study designed to compare the effects of calcium carbonate and of Sevelamer Carbonate on serum AGE levels and OS in patients with stage II-IV diabetic nephropathy.
Sevelamer Carbonate administration in persons with stage II-IV CKD, compared with calcium carbonate administration, will result in at least a:
1. 20% decrease in serum levels of AGE's;
2. 10% decease in inflammatory markers of CRP and VCAM-1, or of OS (AGER1/RAGE) in circulating mononuclear cells.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
Sevelamer Carbonate, Calcium Carbonate
Mount Sinai School of Medicine
Mount Sinai School of Medicine
Published on BioPortfolio: 2014-08-27T03:19:43-0400
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A field of chemistry which pertains to chemical compounds or ions that do not contain the element carbon (with the exception of carbon dioxide and compounds containing a carbonate radical, e.g., calcium carbonate).
Carbonic acid calcium salt (CaCO3). An odorless, tasteless powder or crystal that occurs in nature. It is used therapeutically as a phosphate buffer in hemodialysis patients and as a calcium supplement.
Protein-mineral complexes that comprise substrates needed for the normal calcium-carbonate-phosphate homeostasis. Nanobacteria was the prior name for the particles which were originally thought to be microorganisms.
A plant family of the order Scrophulariales, subclass Asteridae, class Magnoliopsida. It is characterized by simple leaves in opposite pairs, cystoliths (enlarged cells containing crystals of calcium carbonate), and bilaterally symmetrical and bisexual flowers that are usually crowded together. The common name for Ruellia of wild petunia is easily confused with PETUNIA.
A gelatinous membrane overlying the acoustic maculae of SACCULE AND UTRICLE. It contains minute crystalline particles (otoliths) of CALCIUM CARBONATE and protein on its outer surface. In response to head movement, the otoliths shift causing distortion of the vestibular hair cells which transduce nerve signals to the BRAIN for interpretation of equilibrium.
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