A comparative review of the efficacy and safety of established phosphate binders: calcium, sevelamer, and lanthanum carbonate. As a result, oral phosphate binders are used in over 90% of patients with kidney failure, at an annual cost of approximately $750 million (in U.S. dollars) worldwide.1 Historically, treatment with oral phosphate binders was intended to prevent symp - tomatic secondary hyperparathyroidism. Are propensity scores really superior to standard multivariable analysis? [23] found that relatively high serum phosphate concentrations (>3.9 mg/dL) among young men and women (mean age 25 years) were associated with a greater prevalence of coronary artery calcification 15 years later [23]. Studies of serum phosphate concentrations with disease in non-dialysis-requiring CKD populations have yielded mixed results [11–16]. Sinha MD, Turner C, Booth CJ, Waller S, Rasmussen P, Goldsmith DJ, Simpson JM. The Chronic Renal Impairment in Birmingham Phosphate study randomized 109 stage III CKD patients to sevelamer 1600 mg three times per day versus placebo [40]. Therefore, phosphate management is thought to play a pivotal role in health and longevity of CKD patients. The recently approved iron-based products may have a … Chiu YW, Teitelbaum I, Misra M et al. . Yoshida T, Yoshida N, Monkawa T et al. In CKD affected animals, serum phosphate tends to increase and may become more refractory to control using dietary phosphate restriction. In this review, the role of phosphate as a uraemic toxin and the advantages and disadvantages of the currently available phosphate binders are discussed. Reynolds JL, Joannides AJ, Skepper JN et al. 2007 Dec;23(12):3167-75. doi: 10.1185/030079907X242719. containing phosphate binders versus calcium-free phosphate binders: study characteristics Table S20. To achieve this objective, such studies must first account for potential differences in characteristics between treated and untreated individuals. 20. . Animal models provide further evidence linking phosphate overload with medial arterial calcification in kidney failure. 2009 Feb;20(2):397-404 . Goodman WG, Goldin J, Kuizon BD et al. Associations of serum phosphate concentrations with disease, experimental evidence for the calcifying effects of phosphate and the hypothesized central role of phosphate retention in the development of CKD-MBD collectively motivate clinical trials of phosphate binders using clinically relevant outcomes. Epub 2009 Aug 18. If you have stage 5 CKD (and are on dialysis) For adults, your healthcare professional should offer a phosphate binder called calcium acetate first. Am J Kidney Dis. . Block GA, Hulbert-Shearon TE, Levin NW et al. Kovesdy CP, Anderson JE, Kalantar-Zadeh K. Eddington H, Hoefield R, Sinha S et al. Calcium-based phosphate binders are often used for CKD stages 3 to 5; they are inexpensive, but have a potential to cause hypercalcemia. Key characteristics of pragmatic trial designs include the selection of broadly inclusive study populations with minimal exclusion criteria, a focus on clinically relevant outcomes and avoidance of frequent, intense laboratory monitoring and subclinical disease measurements that may discourage retention. Wang S, Alfieri T, Ramakrishnan K et al. . 2009 Oct;54(4):619-37. doi: 10.1053/j.ajkd.2009.06.004. Seifert ME, de las Fuentes L, Rothstein M et al. Which phosphate binder in which CKD patient? For example, Isakova et al. Your comment will be reviewed and published at the journal's discretion. People with chronic kidney disease (CKD) have a reduction in their capacity to remove phosphate from the body via the kidneys, so that phosphate levels in the blood and in body tissues increase as kidney function decreases. These processes collectively result in calcification of the medial blood vessel wall (Mönckeberg's arteriosclerosis) with resultant loss of normal vessel compliance. Published by Oxford University Press on behalf of ERA-EDTA. Many clinical trials in medicine, including nephrology, have found no benefit, or even harm, from treatments that target a single metabolite or metabolic pathway based on biomarker association studies and suspected biological significance to a disease process. Phosphate binders are prescribed to chronic kidney disease (CKD) patients based on associations of serum phosphate concentrations with mortality and calcification, experimental evidence for direct calcifying effects of phosphate on vascular smooth muscle tissue and the central importance of phosphate retention in CKD-mineral and bone disorder (CKD-MBD). [ 6, 7] With … Because of the improved removal of phosphate from the Moderator's view: Phosphate binders in chronic kidney disease patients: a clear ‘No’ at the moment, but stay tuned. Giral H, Caldas Y, Sutherland E et al. These studies utilized non-standard methodologies, obscuring the interpretation of results. Such recommendations necessarily imply some intervention (phosphate binders, dietary modification) for patients whose serum phosphate concentrations fall outside the recommended range, yet clinical evidence for such interventions is absent. For full access to this pdf, sign in to an existing account, or purchase an annual subscription. . J Am Soc Nephrol. (See related article by Bellasi. Complementary studies of chronic dialysis patients observed associations of higher serum phosphate concentrations with coronary artery calcification [8–10], suggesting a potential mechanism for associations with clinical outcomes. Biondi-Zoccai G, Romagnoli E, Agostoni P et al. Thank you for submitting a comment on this article. This problem may be attenuated by newer phosphate binders such as sevelamer hydrochloride and lanthanum carbonate. This medicine will help control the amount of phosphorus your body absorbs from the foods you eat. Moreover, guidelines for ‘recommended’ values are a recognized strategy of the pharmaceutical industry used to promote more frequent laboratory testing, thereby increasing the number of ‘abnormal’ values to be considered for treatment. Observational studies of medication use should further utilize complementary methods to those employed in clinical trials, specifically, commencing follow-up when patients first initiate therapy (incident users) and performing primary analyses according to initial treatment assignment (intention-to-treat). Null findings from these studies should not discourage subsequent trials using clinical endpoints. . Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients, Effects of sevelamer and calcium on coronary artery calcification in patients new to hemodialysis, The progression of coronary artery calcification in predialysis patients on calcium carbonate or sevelamer, A 1-year randomized trial of calcium acetate versus sevelamer on progression of coronary artery calcification in hemodialysis patients with comparable lipid control: the Calcium Acetate Renagel Evaluation-2 (CARE-2) study, Practical clinical trials: increasing the value of clinical research for decision making in clinical and health policy, Pill burden, adherence, hyperphosphatemia, and quality of life in maintenance dialysis patients, Serum phosphorus levels and pill burden are inversely associated with adherence in patients on hemodialysis, Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis, Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease: a randomized controlled trial, A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. Clin Kidney J. 2012 Feb;5(Suppl 1):i62-i70. Therefore, at present, the prolonged use of aluminium-containing phosphate binders in patients with CKD is strongly discouraged, in accordance with recent clinical practice guidelines. Preclinical data have shown that the combination of intestinal phosphate binders with inhibitors of active intestinal phosphate transport may enhance the phosphorus-lowering. This study was supported by a grant from the National Institutes of Health R01 DK094891. . Menon V, Greene T, Pereira AA et al. Epub 2013 Oct 9. CLINCAL INFORMATION See Phosphate Binders Prescribing Information Sheet AREAS OF RESPONSIBILITY Specialist’s Roles and Responsibilities 1. First, the initiation of calcification in cell culture models typically requires substantially high concentrations of phosphate (3.0 mmol = 9.3 mg/dL) under stringent conditions. COVID-19 is an emerging, rapidly evolving situation. Finally, Seifert et al. For adults with stage 4 or 5 CKD who are not on dialysis, the UK Renal Association guidelines recommend that serum phosphate be maintained at between 0.9 and 1.5 mmol/l. B.K. The demise of calcium-based phosphate binders-is this appropriate for children? Intestinal phosphate binders that do not contain calcium are associated with a reduction of mortality in the order of 22%, compared with those that do contain calcium. . Several studies have also demonstrated associations of higher serum phosphate concentrations and with coronary artery calcification, cardiac valve calcification and rapid progression to dialysis in CKD populations [17, 18]. Such trials typically avoid hypervigilant procedures for ensuring compliance with treatment, which are clinically unrealistic, may utilize a no-treatment group in place of a formal placebo and can be completed at relatively lower costs. . The addition of exogenous phosphate to cultured vascular smooth muscle cells and isolated aortic rings causes loss of the smooth muscle phenotype, expression of bone-specific markers and mineralization of the extracellular matrix [30–32]. Plasma phosphate levels are important in the evolution of hyperparathyroidism and ectopic calcification in chronic kidney disease (CKD). Young EW, Albert JM, Satayathum S et al. -, J Am Soc Nephrol. Epub 2020 May 8. However, certain aspects of experimental models temper direct application to human calcification. Melamed ML, Eustace JA, Plantinga L et al. Lanthanum carbonate, a noncalcium phosphate binder, does not appear to improve outcomes in CKD patients who are not yet on dialysis; trial is … The dietary management of calcium and phosphate in children with CKD stages 2-5 and on dialysis-clinical practice recommendation from the Pediatric Renal Nutrition Taskforce. Current evidence is limited to short-term clinical trials using biochemical and subclinical endpoints, pharmacoepidemiologic studies and head-to-head studies that compare different classes of phosphate binders. A central goal of pharmacoepidemiologic studies is to estimate results that would be found in randomized clinical trials of similar individuals [52]. . Advanced coronary and carotid arteriopathy in young adults with childhood-onset chronic renal failure, Serum phosphate levels and mortality risk among people with chronic kidney disease, Relationship of phosphorus and calcium–phosphorus product with mortality in CKD, Outcomes associated with serum phosphorus level in males with non-dialysis dependent chronic kidney disease, Serum phosphate and mortality in patients with chronic kidney disease, Outcomes predicted by phosphorous in chronic kidney disease: a retrospective CKD-inception cohort study, No independent association of serum phosphorus with risk for death or progression to end-stage renal disease in a large screen for chronic kidney disease, High plasma phosphate as a risk factor for decline in renal function and mortality in pre-dialysis patients, Association of serum phosphate with vascular and valvular calcification in moderate CKD, Dietary intake of phosphorus modulates the circadian rhythm in serum concentration of phosphorus. 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