Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients

Chertow, Glenn M.; Burke, Steven K.; Raggi, Paolo; Group, for the Treat to Goal Working

doi:10.1046/j.1523-1755.2002.00434.x

Cited by 1,344 publications

(1,218 citation statements)

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“…The use of CART also identified the relationship between serum calcium concentrations and defective mineralization. Indeed, low serum calcium levels and high serum PTH values were the strongest predictors of mineralization defect in patients with bone turnover within the normal range, a finding that should be taken into consideration in view of the availability of therapeutic agents, such as calcium-free phosphate binders (10,27) and calcimimetic agents (28), which maintain serum calcium levels within the lower normal range. None of the patients included in this analysis received any of these agents before bone biopsy.…”

Section: Discussionmentioning

confidence: 99%

Value of the New Bone Classification System in Pediatric Renal Osteodystrophy

Bakkaloğlu

Wesseling‐Perry²,

Pereira³

et al. 2010

Clinical Journal of the American Society of Nephrology

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Background and objectives: Although lesions of renal osteodystrophy have traditionally been defined by bone turnover, alterations in skeletal mineralization and volume are also prevalent and may contribute to significant morbidity in patients with chronic kidney disease (CKD). The study presented here was undertaken to compare the traditional spectrum of renal osteodystrophy defined by bone turnover to a new classification system that includes T (turnover), M (mineralization), and V (volume) and to determine the value of biochemical parameters as predictors of specific TMV lesions.Design, setting, participants, & measurements: Pediatric patients (n ‫؍‬ 161) treated with peritoneal dialysis were enrolled into the study.Results: Increased bone turnover and abnormal mineralization were prevalent (57% and 48%, respectively); bone volume was normal or increased in all subjects. Predictive algorithms for different skeletal diagnoses were established by Classification and regression tree analysis. Serum parathyroid hormone (PTH) less than 400 pg/ml in combination with alkaline phosphatase values less than 400 IU/L provided the highest correct prediction rate for patients with both normal bone turnover and normal mineralization. Levels of PTH were higher and serum calcium levels were lower in patients with defective mineralization, irrespective of bone turnover.Conclusions: Although no single biochemical marker is able to provide a complete assessment of renal osteodystrophy, a combination of serum calcium, alkaline phosphatase, and PTH levels may lead to a more precise noninvasive assessment of turnover and mineralization abnormalities in this population.

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Section: Discussionmentioning

confidence: 99%

Value of the New Bone Classification System in Pediatric Renal Osteodystrophy

Bakkaloğlu

Wesseling‐Perry²,

Pereira³

et al. 2010

Clinical Journal of the American Society of Nephrology

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“…Moreover, adverse CVD events in CKD are often due to heart failure, which may be related to higher serum phosphorus, at least in part because of its effect to promote cardiac valvular and muscle calcification (7,15,23,24). Clinical trials of phosphate reduction have been limited by selection of only participants with ESRD and insufficient clinical outcomes data to draw firm conclusions (25,26). Observational human data combined with experimental studies make a case for testing effects of treatments that reduce phosphate on CVD outcomes in patients who are in earlier stages of CKD or perhaps even in those who do not have CKD but have CAC.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal Relationships among Coronary Artery Calcification, Serum Phosphorus, and Kidney Function

Tuttle

Short

2009

Clinical Journal of the American Society of Nephrology

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Background and objectives: Coronary artery calcification (CAC) is common in advanced chronic kidney disease (CKD), yet its onset and time course are uncertain. The study objective was to assess longitudinal relationships among CAC, kidney function, and traditional and putative cardiovascular disease (CVD) risk factors.Design, setting, participants, & measurements: This is a prospective cohort analysis from the Spokane Heart Study, a long-term observational study of community-dwelling adults who were assessed every 2 yr for CAC (electron-beam computed tomography), CVD risk factors, and laboratory testing. Estimated GFR (eGFR) was determined by the reexpressed Modification of Diet in Renal Disease equation.Results: CAC was present in 28% (245 of 883) at baseline. After 6 yr, new-onset CAC developed in 33% (122 of 371); severity increased from a median CAC score of 38 to 152 in those with baseline CAC. Neither eGFR (101 ؎ 34 versus 104 ؎ 31 ml/min per 1.73 m 2 , respectively) nor serum phosphorus (3.25 ؎ 0.49 versus 3.29 ؎ 0.48 mg/dl, respectively) differed by CAC presence or absence at baseline; however, multivariate models (generalized estimating equations for incidence and prevalence) revealed that independent predictors of CAC over time were greater baseline CAC scores, higher serum phosphorus levels, lower eGFR levels, and traditional CVD risk factors. Each 1-mg/dl increase in phosphorus imparted odds ratios for CAC of 1.61 (incidence) and 1.54 (prevalence), risks comparable to traditional CVD risk factors.Conclusions: CAC becomes more frequent and severe over time. Higher levels of serum phosphorus and reduced kidney function independently predicted CAC.

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“…Chertow et al (23) and Asmus et al (24) demonstrated that sevelamer hydrochloride treatment compared with calcium carbonate resulted in a decreased rate of increase in vascular calcium in dialysis patients. Sevelamer therapy in humans often is associated with a reduction in serum cholesterol (23,25) as observed in the studies reported here. Phan et al (26) demonstrated that sevelamer hydrochloride decreased the calcification of atherosclerotic plaques during an 8-wk prevention trial in apolipoprotein E-deficient mice that were made uremic by the procedure used in our study.…”

Section: Discussionmentioning

confidence: 99%

Reversal of the Adynamic Bone Disorder and Decreased Vascular Calcification in Chronic Kidney Disease by Sevelamer Carbonate Therapy

Mathew

Lund

Strebeck

et al. 2007

Journal of the American Society of Nephrology

103

105

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A model of chronic kidney disease (CKD)-induced vascular calcification (VC) that complicates the metabolic syndrome was produced. In this model, the metabolic syndrome is characterized by severe atherosclerotic plaque formation, hypertension, type 2 diabetes, obesity, and hypercholesterolemia, and CKD stimulates calcification of the neointima and tunica media of the aorta. The CKD in this model is associated the adynamic bone disorder form of renal osteodystrophy. The VC of the model is associated with hyperphosphatemia, and control of the serum phosphorus both in this animal model and in humans has been preventive in the development of VC. This article reports studies that demonstrate reduction of established VC by the addition of sevelamer carbonate to the diets of this murine metabolic syndrome model with CKD. Sevelamer, besides normalizing the serum phosphorus, surprisingly, reversed the CKD-induced trabecular osteopenia. Sevelamer therapy increased osteoblast surfaces in the metaphyseal trabeculae of the tibia and femur. It also increased osteoid surfaces and, importantly, bone formation rates. In addition, sevelamer was found to be effective in decreasing serum cholesterol levels. These results suggest that sevelamer may have important actions in decreasing diabetic and uremic vasculopathy and that sevelamer carbonate may be capable of increasing bone formation rates that are suppressed by diabetic nephropathy. 18: 122-130, 200718: 122-130, . doi: 10.1681 P rogression of diabetic nephropathy (DN) generally is considered in terms of progressive loss of kidney function until end-stage kidney failure occurs and renal replacement therapy begins. However, DN is a systemic disease, and it also is fatal. Indeed, more patients with DN die before reaching the need for dialysis than accrue to modalities of renal replacement therapy (1-3). Cardiovascular mortality in patients with chronic kidney disease (CKD) is extremely high (1,4). Conventional risk factors that are characteristic of the metabolic syndrome (5), such as hypertension, dyslipidemia, insulin resistance, and overt diabetes, are highly prevalent in CKD, but other risk factors with additive affects that are more specific to the uremic milieu also have been identified (6 -8). J Am Soc NephrolOne is the presence of vascular calcification (VC) (9), a form of heterotopic mineralization that is predictive of cardiovascular mortality (10,11) and is both common and severe in CKD (12). The VC of the tunica media that is seen in CKD is similar to that observed in type 2 diabetes without DN, and when CKD is added to diabetes through DN, the cardiovascular risk is at least additive of that of CKD plus diabetes; in other words, extreme. We have developed an animal model of VC that is worsened by CKD (13). The model is partial renal ablation in the LDL receptor-deficient (LDLRϪ/Ϫ) mouse that is fed high-fat/ cholesterol diets. This model resembles the clinical situation of CKD's complicating the metabolic syndrome, because the mice have obesity, hypertension, insulin...

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Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients

Abstract: Compared with calcium-based phosphate binders, sevelamer is less likely to cause hypercalcemia, low levels of PTH, and progressive coronary and aortic calcification in hemodialysis patients.

Cited by 1,344 publications

References 33 publications

Value of the New Bone Classification System in Pediatric Renal Osteodystrophy

Value of the New Bone Classification System in Pediatric Renal Osteodystrophy

Longitudinal Relationships among Coronary Artery Calcification, Serum Phosphorus, and Kidney Function

Reversal of the Adynamic Bone Disorder and Decreased Vascular Calcification in Chronic Kidney Disease by Sevelamer Carbonate Therapy

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