A Randomized Crossover Trial Comparing Sevelamer With Calcium Acetate in Children With CKD

Pieper, Anne-Kathrin; Haffner, Dieter; Höppe, Bernd; Dittrich, Katalin; Offner, G.; Bonzel, Klaus-Eugen; John, U; Fründ, Stefan; Klaus, Günter; Stübinger, Amrey; Düker, Gesche; Querfeld, Uwe

doi:10.1053/j.ajkd.2005.12.039

Cited by 77 publications

(56 citation statements)

References 25 publications

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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: Discussionsupporting

confidence: 52%

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

102

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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Section: Discussionsupporting

confidence: 52%

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

102

105

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“…This readily occurs in children and patients with CKD (25). In states of reduced GFR, even a normal input of calcium into the circulation from gut or bone can result in hypercalcemia.…”

Section: Renal Calcium Excretionmentioning

confidence: 99%

“…Absorptive hypercalcemia readily develops in children and patients with chronic kidney disease (CKD) when they receive amounts of dietary calcium that exceed the ability of their kidneys to filter and excrete the calcium load (25).…”

Section: Intestinal Calcium Absorptionmentioning

confidence: 99%

Calcium Metabolism in Health and Disease

Peacock

2010

Clinical Journal of the American Society of Nephrology

677

502

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This brief review focuses on calcium balance and homeostasis and their relationship to dietary calcium intake and calcium supplementation in healthy subjects and patients with chronic kidney disease and mineral bone disorders (CKD-MBD). Calcium balance refers to the state of the calcium body stores, primarily in bone, which are largely a function of dietary intake, intestinal absorption, renal excretion, and bone remodeling. Bone calcium balance can be positive, neutral, or negative, depending on a number of factors, including growth, aging, and acquired or inherited disorders. Calcium homeostasis refers to the hormonal regulation of serum ionized calcium by parathyroid hormone, 1,25-dihydroxyvitamin D, and serum ionized calcium itself, which together regulate calcium transport at the gut, kidney, and bone. Hypercalcemia and hypocalcemia indicate serious disruption of calcium homeostasis but do not reflect calcium balance on their own. Calcium balance studies have determined the dietary and supplemental calcium requirements needed to optimize bone mass in healthy subjects. However, similar studies are needed in CKD-MBD, which disrupts both calcium balance and homeostasis, because these data in healthy subjects may not be generalizable to this patient group. Importantly, increasing evidence suggests that calcium supplementation may enhance soft tissue calcification and cardiovascular disease in CKD-MBD. Further research is needed to elucidate the risks and mechanisms of soft tissue calcification with calcium supplementation in both healthy subjects and CKD-MBD patients.

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“…However, the use of sevelamer HCl has been associated with a dose-dependent metabolic acidosis in both pediatric and adult dialysis patients [9,11]. This side effect is concerning in children, as chronic metabolic acidosis is considered a potential risk factor for poor growth.…”

Section: Introductionmentioning

confidence: 99%

“…Although this process is multifactorial, the use of calcium-based phosphate binders has been associated with the development of vascular calcifications in adult and pediatric patients receiving dialysis [3,6]. Sevelamer hydrochloride (HCl), on the other hand, has been shown to be a safe and effective phosphate binder, providing the same control of skeletal lesions associated with secondary hyperparathyroidism as calcium-based binder therapy [7][8][9]. Furthermore, sevelamer HCl has been associated with decreased progression of vascular calcifications in adult patients undergoing hemodialysis [6,10].…”

Section: Introductionmentioning

confidence: 99%

Sevelamer carbonate increases serum bicarbonate in pediatric dialysis patients

et al. 2010

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Sevelamer hydrochloride (HCl), a calcium-free phosphate binder, is increasingly used due to concerns related to calcium exposure and the development of vascular calcifications. However, a common side effect of sevelamer HCl, metabolic acidosis, is particularly concerning in children, as it can contribute to poor growth. Sevelamer carbonate is now available and has been shown to increase serum bicarbonate in adult patients. We conducted a prospective single-center study of pediatric dialysis patients comparing serum bicarbonate before and 3 months after a switch from sevelamer HCl to sevelamer carbonate. Inclusion criteria were a minimum of 3 months of dialysis therapy and either a serum bicarbonate <20 mmol/L or the need for sodium bicarbonate supplementation. Ten hemodialysis and 14 peritoneal dialysis patients, aged 16± 3 years, were enrolled. Whereas serum calcium and phosphorus remained unchanged, serum bicarbonate increased from 20 (17.2-22.0) to 24.5 (20.75-26) mmol/L (p<0.001) after 3 months of sevelamer carbonate therapy. Sodium bicarbonate supplementation was stopped in all patients (n=10), reducing the mean daily sodium intake by an average of 2.3 g per patient. These results demonstrate that sevelamer carbonate is an effective phosphate binder that improves acid-base status in pediatric dialysis patients.

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A Randomized Crossover Trial Comparing Sevelamer With Calcium Acetate in Children With CKD

Cited by 77 publications

References 25 publications

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

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

Calcium Metabolism in Health and Disease

Sevelamer carbonate increases serum bicarbonate in pediatric dialysis patients

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