Article

Efficacy and Tolerability of Sevelamer Carbonate in Hyperphosphatemic Patients Who Have Chronic Kidney Disease and Are Not on Dialysis

Nephrologische Klinik, Klinikum Coburg gGmbH, Ketschendorfer Strasse 33, 96450 Coburg, Germany.
Clinical Journal of the American Society of Nephrology (Impact Factor: 5.25). 07/2008; 3(4):1125-30. DOI: 10.2215/CJN.05161107
Source: PubMed

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.

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    • "Such studies are furthers hampered by the fact that phosphate-lowering effects are not clearly visible, because a decline in phosphaturia may blunt the changes in circulating phosphate levels. The efficacy of sevelamer carbonate in predialysis CKD patients was recently examined in 19 nephrology centers across Northern Europe and Australia in a single-arm study approach with a poststudy washout period [27]. "
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    ABSTRACT: When compared to the available information for patients on dialysis (CKD stage 5D), data on the epidemiology and appropriate treatment of calcium and phosphate metabolism in the predialysis stages of chronic kidney disease (CKD) are quite limited. Perceptible derangements of calcium and phosphate levels start to become apparent when GFR falls below 30 mL/min in some, but not all, patients. However, hyperphosphatemia may be a significant morbidity and mortality risk predictor in predialysis CKD stages. The RIND study, evaluating progression of coronary artery calcification in incident hemodialysis patients, indirectly demonstrated that vascular calcification processes start to manifest in CKD patients prior to the dialysis stage, which may be closely linked to early and invisible derangements in calcium and phosphate homeostasis. Novel insights into the pathophysiology of calcium and phosphate handling such as the discovery of FGF23 and other phosphatonins suggest that a more complex assessment of phosphate balance is warranted, possibly including measurements of fractional phosphate excretion and phosphatonin levels in order to appropriately evaluate disordered metabolism in earlier stages of kidney disease. As a consequence, early and preventive treatment approaches may have to be developed for patients in CKD stages 3-5 to halt progression of CKD-MBD.
    05/2011; 2011:970245. DOI:10.4061/2011/970245
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    • "In a recent open label, single arm study, Ketteler et al (2008) administered sevelamer carbonate at a mean actual daily dosage of 5.5 g (6–7 sevelamer carbonate 800 mg tablets per day) to CKD patients with mean serum P Ն 6.2 ± 0.8 mg/dL and not under replacement therapy. A signifi cant 1.4 mg/dL decrease in serum P was observed over an 8-week treatment, after a 2-week washout for patients previously on other phosphate binders, mainly calcium-based phosphate binders. "
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    ABSTRACT: Sevelamer carbonate is an anion exchange pharmaceutical, developed to improve on the performance of the non-absorbable, non-calcium, and metal-free phosphate binder sevelamer hydrochloride. Sevelamer carbonate is expected not to worsen metabolic acidosis, as previously reported during long-term treatment with sevelamer hydrochloride in hemodialysis (HD) patients. Carbonate is the alternate counterion to chloride on the sevelamer polymeric backbone, but the active poly(allylamine) responsible for phosphate (PO₄) binding remains unaltered. Therefore, sevelamer carbonate is expected to reduce elevated serum phosphorus level, similarly to sevelamer hydrochloride. Sevelamers are prescribed in uremic HD patients to control hyperphosphatemia, but the carbonate has also been proposed for the treatment of chronic kidney disease (CKD) non-dialysis patients. Although hyperphosphatemia is regarded as a main contributor to increased mortality in the HD population because of cardiovascular calcification, metabolic acidosis has also been advocated as a major player in the increased mortality in this population, by engendering malnutrition, negative nitrogen balance, and inflammation. This paper reviews the evidence showing that sevelamer carbonate is as good as sevelamer hydrochloride in terms of hyperphosphatemia control in CKD, but with a better outcome in serum bicarbonate balance.
    Therapeutics and Clinical Risk Management 09/2008; 4(4):821-6. · 1.47 Impact Factor
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    ABSTRACT: Vom Gesamtkörperphosphat (etwa 600–700g) finden sich 80–85% im Knochen, 15% sind in Weichteilen, Blut, ECV und ICV in Form verschiedenster anorganischer und insbesondere organischer Phosphatverbindungen enthalten. Da etwa die Hälfte des im Darm resorbierten Phosphates passiv, also nicht kontrolliert resorbiert wird, kommt beim Nierengesunden der renalen Phosphatausscheidung eine entscheidende Bedeutung für die Phosphathomöostase im Organismus zu. Der Ausfall der renalen Regulation bei Dialysepatienten führt zu dem Risiko der Phosphatanhäufung im Organismus, was entscheidend zu der extraossären Kalzifikation einschließlich kardiovaskulärer Komplikationen und Mortalitätssteigerung beiträgt. Da bei der Dialyse nicht genug Phosphat eliminiert werden kann, muss die intestinale Phosphatresorption durch Phosphatbinder reduziert werden. Diskutiert wird die Anwendung verschiedener Phosphatbinder wie kalzium-, aluminium-, eisen- und lanthanhaltige wie auch kalzium- und metallfreie Phosphatbinder einschließlich Nikotinsäure und Chitosankaugummi. The total body phosphate of approximately 600–700g is distributed to 80–85% in bones and 15% in soft tissues, blood, ECV and ICV in the form of various inorganic and organic phosphate bonds. As approximately 50% of the phosphate uptake from the intestines is passive and uptake is therefore uncontrolled, in normal healthy kidneys the renal excretion of phosphate is of great significance for phosphate homeostasis within the organism. Loss of this renal regulation in dialysis patients leads to the risk of phosphate accumulation in the body and plays a decisive role in extra-osseal calcification including cardiovascular complications and increased mortality. Because insufficient phosphate can be eliminated by dialysis, intestinal phosphate uptake must be reduced by phosphate binders. The application of various phosphate binders, such as calcium-containing phosphate binders or those containing aluminum, iron and lanthanum as well as calcium and metal-free binders including nicotinic acid and chitosan chewing gum will be discussed.
    Der Nephrologe 09/2009; 4(5):401-410. DOI:10.1007/s11560-009-0292-x
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