Long-term effects of calcium carbonate and 2.5 mEq/liter calcium dialysate on mineral metabolism

Slatopolsky, Eduardo; Weerts, Carol; Norwood, Kathryn; Giles, Karla; Fryer, Patricia; Finch, Jane; Windus, David W.; Delmez, James A.

doi:10.1038/ki.1989.277

Cited by 134 publications

(55 citation statements)

References 23 publications

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“…Calcium carbonate contains a high proportion of elemental calcium (40%), and hypercalcemia can occur when given at escalating doses (33), when administered concomitantly with vitamin D (which increases gastrointestinal [GI] absorption of calcium), or with use of higher dialysate calcium concentrations (31,34). Furthermore, the proportion of calcium absorbed from phosphate-binder intake dramatically increases when there is unsynchronized administration in relation to meals.…”

Section: Calcium Carbonatementioning

confidence: 99%

Control of Hyperphosphatemia among Patients with ESRD

Coladonato¹

2005

Journal of the American Society of Nephrology

102

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Derangements of mineral metabolism occur during the early stages of chronic kidney disease (CKD). Hyperphosphatemia develops in the majority of patients with ESRD and has long been associated with progression of secondary hyperparathyroidism and renal osteodystrophy. More recent observational data have associated hyperphosphatemia with increased cardiovascular mortality among dialysis patients. Adequate control of serum phosphorus remains a cornerstone in the clinical management of patients with CKD not only to attenuate the progression of secondary hyperparathyroidism but also possibly to reduce the risk for vascular calcification and cardiovascular mortality. These measures include dietary phosphorus restriction, dialysis, and oral phosphate binders. Dietary restriction is limited in advanced stages of CKD. Phosphate binders are necessary to limit dietary absorption of phosphorus. Aluminum hydroxide is an efficient binder; however, its use has been nearly eliminated because of concerns of toxicity. Calcium salts are inexpensive and have been used effectively worldwide as an alternative to aluminum. Concerns of calcium overload have led to the investigation of alternatives. Currently, only two Food and Drug Administration-approved noncalcium, nonaluminum binders are available. Sevelamer hydrochloride is an exchange resin and was not as effective as calcium acetate in meeting new guideline recommendations in one double-blind clinical trial. Lanthanum carbonate is a rare earth element and has been studied less extensively. Concerns of long-term administration and toxicity exist. Furthermore, these agents are significantly more expensive than calcium salts, which may contribute to patient noncompliance.

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Section: Calcium Carbonatementioning

confidence: 99%

Control of Hyperphosphatemia among Patients with ESRD

Coladonato¹

2005

Journal of the American Society of Nephrology

102

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“…Each component of this combined treatment strategy addresses abnormalities responsible for the pathogenesis of hyperparathyroidism, but each has limitations due to potential undesirable side effects at doses required to effectively suppress PTH hypersecretion (3)(4)(5)(6). In this regard, treatment with vitamin D sterols is often complicated by hypercalcemia and hyperphosphatemia (7)(8)(9)(10), resulting in elevate calcium ϫ phosphorus levels, predisposition to soft tissue calcification, and increased mortality risk in the ESRD population (11)(12)(13)(14)(15).…”

mentioning

confidence: 99%

The Calcimimetic AMG 073 as a Potential Treatment for Secondary Hyperparathyroidism of End-Stage Renal Disease

Quarles¹,

Sherrard²,

Adler³

et al. 2003

Journal of the American Society of Nephrology

240

185

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Abstract. Current treatment of secondary hyperparathyroidism in chronic kidney failure with calcium and active vitamin D is potentially limited by hypercalcemia and hyperphosphatemia. AMG 073 represents a new class of compounds for the treatment of hyperparathyroidism known as calcimimetics, which reduce parathyroid hormone (PTH) synthesis and secretion by increasing the sensitivity of the parathyroid calcium-sensing receptor (CaR) to extracellular calcium. The current study evaluates the efficacy and safety of AMG 073 when added to conventional treatment of secondary hyperparathyroidism in end-stage renal disease (ESRD). Seventy-one hemodialysis patients with uncontrolled secondary hyperparathyroidism, despite standard therapy with calcium, phosphate binders, and active vitamin D sterols, were treated in this 18-wk, dosetitration study with single daily oral doses of AMG 073/ placebo up to 100 mg. Changes in plasma PTH, serum calcium, serum phosphorus, and calcium ϫ phosphorus levels were compared between AMG 073 and placebo groups. Mean PTH decreased by 33% in the AMG 073 patients compared with an increase of 3% in placebo patients (P ϭ 0.001). A significantly greater proportion of AMG 073 patients (44%) had a mean PTH Յ 250 pg/ml compared with placebo patients (20%; P ϭ 0.029). Also, a significantly greater proportion of AMG 073 patients (53%) had a decrease in PTH Ն30% compared with placebo patients (23%; P ϭ 0.009). Calcium ϫ phosphorus levels decreased by 7.9% in AMG 073 patients compared with an increase of 11.3% in placebo patients (P ϭ 0.013). Adverse event rates were low and mostly mild to moderate in severity; however, the incidence of vomiting was higher in AMG 073 patients. In this study, the calcimimetic AMG 073 at doses up to 100 mg for 18 wk provided a safe and effective means to attain significant reductions in PTH and calcium ϫ phosphorus levels in ESRD patients. AMG 073 represents a novel and promising therapy to improve the management of secondary hyperparathyroidism.The current standard treatment for secondary hyperparathyroidism in ESRD uses calcium supplementation, phosphate binders, and active vitamin D sterols in various combinations to attempt correction of hypocalcemia, hyperphosphatemia, and 1,25 (OH) 2 vitamin D 3 deficiency (1,2). Each component of this combined treatment strategy addresses abnormalities responsible for the pathogenesis of hyperparathyroidism, but each has limitations due to potential undesirable side effects at doses required to effectively suppress PTH hypersecretion (3-6). In this regard, treatment with vitamin D sterols is often complicated by hypercalcemia and hyperphosphatemia (7-10), resulting in elevate calcium ϫ phosphorus levels, predisposition to soft tissue calcification, and increased mortality risk in the ESRD population (11-15). Large doses of orally administered calcium to control hyperphosphatemia also predispose patients to episodes of hypercalcemia, chronic positive calcium balance, and increased soft tissue calcification in dialysis patients (15,...

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“…Essa mudança foi suportada por outros estudos que mostraram que o uso combinado de carbonato de Ca, calcitriol e Ca no dialisato de 2,5 mEq/L era efetivo para tratar o HPS. [9][10][11] Mais recentemente, sobrecarga de Ca, mesmo na ausência de hipercalcemia, foi associada a maior risco de calcificação vascular, doença óssea de baixa remodelação e mortalidade, aumentando a preocupação com o ganho de Ca pelos pacientes em diálise, seja do quelante ou do dialisato. 12,13 Além disso, a associação de maior risco de mortalidade em pacientes com níveis mais elevados de Ca observado em estudo observacional reforçou esta ideia.…”

Section: Racionalunclassified