Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiovascular disease is the primary cause of morbidity and mortality in chronic kidney disease (CKD). Nontraditional uremia-related risk factors as well as traditional risk factors may contribute to the unique features of cardiovascular disease in patients with CKD. Vascular calcification is a prominent feature of arterial disease in CKD and may have an impact on cardiovascular mortality through modulating both arteriosclerosis (arterial stiffening) and atherosclerosis. There are two pathophysiological processes involved in the development of vascular calcification: apoptosis and phenotypic transition to chondrocytes or osteoblasts (chodro/osteogenic differentiation). In CKD, abnormal mineral metabolism, predominantly hyperphosphatemia and hypercalcemia, facilitates progression of vascular calcification in association with functional disturbances of its inhibitory molecules (inhibitors of vascular calcification) such as pyrophosphate, matrix Gla protein, fetuin-A, and osteoprotegerin.
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PMID:Vascular calcification in chronic kidney disease: pathogenesis and clinical implications. 1912 77

Low intake of dietary calcium is related to bone loss and fragility fracture in older adults, especially postmenopausal women. Contradictory findings have been reported from studies that investigated the association between calcium supplementation and hypertension and the risk of stroke and cardiovascular disease. Misinterpretation of findings from studies that are not primarily designed to address these issues might overshadow the benefits of dietary calcium. Until well-designed studies address the current uncertainties, the possible detrimental effect (e.g., hypercalcemia and its complications) of higher-than-recommended calcium intake should be balanced against the likely benefits of calcium on bone, particularly in elderly women.
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PMID:Is calcium supplementation a risk factor for cardiovascular diseases in older women? 1956 3

Management of secondary hyperparathyroidism (SHPT) in chronic kidney disease patients on hemodialysis (HD) can be challenging. Conventional treatments can lead to hypercalcemia and hyperphosphatemia, both of which are associated with vascular and soft tissue calcification and increased risk of cardiovascular disease. We report the effect of treatment with the Type II calcimimetic cinacalcet on vascular calcification in a HD patient with SHPT. A 40-year-old male with a 24-year history of kidney failure secondary to mesangial proliferative glomerulonephritis, commenced HD in October 2004 following chronic graft dysfunction. The patient was admitted to hospital with renal insufficiency and metabolic abnormalities. An anatomopathological study showed calcium (Ca) deposits in the alveolar septa, bronchial wall and pulmonary arterioles. Parathyroid methoxy isobutyl isonitrile (MIBI) scintigraphy revealed multiglandular parathyroid disease and an ectopic gland behind the sternal notch. Serum intact parathyroid hormone (iPTH) was repeatedly found to be > or = 2,500 pg/ml, and was accompanied by significant abnormalities in phosphorus (P) and Ca metabolism which were difficult to control. The patient was initially treated with sevelamer, low dose calcium carbonate, a low P and reduced protein diet and high doses of intravenous erythropoietin. In addition, he received HD with a high efficiency membrane for 4.5 hours, 4-times weekly. Treatment with cinacalcet was initiated at 30 mg/day and adjusted to achieve National Kidney Foundation Kidney Disease Outcomes Quality Initiative targets for iPTH, P, Ca and Ca-P product. One year following cinacalcet treatment, a chest x-ray showed a moderate reduction in Ca deposits, a bone X-ray showed a significant reduction in vascular calcifications, and parathyroid MIBI scintigraphy showed a disappearance of ectopic focus and minimal remains of glands. Significant reductions in calcemia were controlled by concomitant modifications to oral Ca supplementation, Ca concentration in the dialysis liquid, and administration of paricalcitriol. In the second year of treatment, iPTH was maintained within the target range, with moderate rises in P and stabilization of serum Ca. An echocardiogram showed an improvement in left ventricular hypertrophy. Chest and hand X-rays showed a progressive reduction in calcifications. Radiology showed an improvement in bone morphology, with reduced trabeculation and better cortical definition in the phalanx bones. In conclusion, the changes in iPTH, P and Ca associated with cinacalcet treatment were accompanied by reduced vascular and soft tissue calcification in this patient. There were no cardiovascular events and the patient experienced a marked improvement in quality of life.
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PMID:Cinacalcet reduces vascular and soft tissue calcification in secondary hyperparathyroidism (SHPT) in hemodialysis patients. 1920 18

Decline in renal function is related directly to cardiovascular mortality. However, traditional risk factors do not fully account for the high mortality in these patients. Activated vitamin D, a hormone produced by the proximal convoluted tubule of the kidney, appears to have beneficial effects beyond suppressing parathyroid hormone (PTH). However, activated vitamin D also can cause hypercalcemia and hyperphosphatemia in chronic kidney disease. Newer agents such as vitamin D receptor activators (eg, paricalcitol) suppress PTH with reduced risk of hypercalcemia and hyperphosphatemia. Recent evidence from animal and preliminary human studies supports an association between vitamin D receptor activators and reduced risk of cardiovascular disease deaths, irrespective of PTH levels. New pathways of vitamin D regulation also have been discovered, involving fibroblast growth factor-23 and klotho. Although considerable work has been performed to advance our understanding of the effects of vitamin D in health and chronic kidney disease, more investigations and randomized trials need to be performed to elucidate the mechanistic underpinnings of these effects.
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PMID:Role of vitamin D in chronic kidney disease. 1937 2

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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PMID:Calcium metabolism in health and disease. 2008 99

Calcimimetics, which activate the extracellular calcium (Ca(o)(2+))-sensing receptor in the parathyroid and other tissues participating in Ca(o)(2+) homeostasis, were the first described allosteric activators of a G-protein-coupled receptor. Cinacalcet, the only calcimimetic currently approved for human use, is used clinically for treating secondary hyperparathyroidism (e.g., overactivity of parathyroid glands) in patients being dialyzed for chronic kidney disease. By sensitizing the parathyroids to Ca(o)(2+), cinacalcet lowers the circulating parathyroid hormone (PTH) level. It also reduces serum calcium and phosphate, changes increasing the percentage of patients achieving the guidelines recommended by the National Kidney Foundation (NKF) for these minerals. Studies are underway addressing whether better adherence to these guidelines in patients receiving cinacalcet reduces cardiovascular disease and related mortality, which are both common is the dialysis population. The second approved use of cinacalcet is for treating hypercalcemia in patients with inoperable parathyroid carcinoma. In this setting, it provides the first medical therapy chronically lowering serum calcium concentration in this condition, albeit not to normal in most patients. Its effect on the long-term prognosis of these patients, if any, is presently unclear. "Off-label" administration of cinacalcet [i.e., not yet approved by the US Food and Drug Administration (FDA)] effectively lowers serum calcium and/or PTH in various other forms of hyperparathyroidism and increases serum phosphate in renal phosphate-wasting syndromes by reducing PTH-induced phosphaturia. In the future, the drug could conceivably be utilized to modulate the activity of the CaSR in other tissues (i.e., kidney, colon) in therapeutically desirable ways.
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PMID:Clinical utility of calcimimetics targeting the extracellular calcium-sensing receptor (CaSR). 2038 29

A large and rapidly expanding body of scientific literature exists on the roles of vitamin D in maintaining optimal health and reducing the risk of chronic and infectious diseases. Serum 25-hydroxyvitamin D [25(OH)D] levels for optimal health are in the range of 100-150 nmol/L; mean population values in The Netherlands are around 50-63 nmol/L. Health problems for which there exists good observational evidence and some randomized controlled trial evidence that vitamin D reduces risk include many types of cancer, cardiovascular disease, diabetes mellitus, bacterial and viral infections, autoimmune diseases, osteoporosis, falls and fractures, dementia, congestive heart failure, and adverse pregnancy outcomes. Reductions in incidence and mortality rates for various diseases and all-cause mortality rates can be determined from ecological, observational and cross-sectional studies and randomized controlled trials. For The Netherlands, raising mean serum 25(OH)D levels to 105 nmol/L is estimated to reduce specific disease rates by 10-50% and all-cause mortality rates by 18%. To raise serum 25(OH)D levels by this amount, inhabitants in The Netherlands would have to increase vitamin D production or oral intake by 2500-4000 IU/day. Doing so would pose only minimal increased risks of melanoma or skin cancer or hypercalcemia.
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PMID:Health benefits of higher serum 25-hydroxyvitamin D levels in The Netherlands. 2039 63

The death rate from cardiovascular disease for dialysis patients is much higher than the general population, regardless of age. Observational data indicate that there is a close inter-relationship between progressive renal dysfunction in patients with chronic kidney disease cardiovascular disease and mortality. Continuously evidence indicates that deficiencies in vitamin D receptor activation represents one of key players in adversely affecting cardiovascular health, as well as inducing to secondary hyperparathyroidism in chromic kidney disease patients. Vitamin D receptors are widely expressed throughout the body and modulations of vitamin D levels results in correlative regulatory effects on mineral metabolism homeostasis, cardiovascular disease, and vascular calcification. The management of SHPT has developed enormously in recent years and different drug classes are available to treat this disease. Potentially, selective VDR activators not only reduce serum parathyroid hormone levels minimizing the risk of hypercalcemia and hyperphosphatemia, but also may improve patient health, reducing the risk of cardiovascular disease.
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PMID:The role of vitamin D receptor activation in chronic kidney disease. 2041 Oct 52

Clinical trials of vitamin D supplementation published from 2000 to 2009 are reviewed, with an emphasis on changes in serum calcium levels. In these trials, vitamin D supplementation often resulted in modest increases in serum calcium levels, but rarely caused hypercalcemia. Although hypercalcemia is considered to be the only toxicity of vitamin D, many prospective studies have demonstrated associations between high normocalcemia (serum calcium levels that are high but fall within the normal reference range) and premature mortality, predominantly from cardiovascular disease. These findings suggest that high normocalcemia may represent a more sensitive index of the long-term toxicity associated with vitamin D supplementation than hypercalcemia. Therefore, efforts to chemoprevent diseases with vitamin D must consider the potential health risks associated with high normocalcemia.
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PMID:Recent clinical trials of vitamin D3 supplementation and serum calcium levels in humans: Implications for vitamin D-based chemoprevention. 2049 63

Left uncontrolled, persistent post-kidney transplant hyperparathyroidism (HPT) may lead to or exacerbate pre-existing bone and cardiovascular disease. Parathyroidectomy has long been the primary treatment option for long-term uncontrolled HPT in post-kidney transplant patients. However, patients with contraindications for surgery and parathyroidectomy-associated complications, including graft loss, highlight the need for other approaches. Conventional medical therapies have limited impact on serum calcium (Ca) and parathyroid hormone (PTH) levels. Bisphosphonates and calcitonin, used to spare bone loss, and phosphorus supplementation, to correct hypophosphatemia, do not directly regulate PTH or Ca. Although vitamin D supplementation can reduce PTH, it is often contraindicated because of hypercalcemia. Studies of the calcimimetic cinacalcet in patients with post-kidney transplant HPT suggest that it can rapidly reduce serum PTH and Ca concentrations while increasing serum phosphorus concentrations toward the normal range. Although the clearest application for cinacalcet is the non-surgical treatment of hypercalcemic patients with persistent HPT, current indications for other transplant patients are as yet uncertain. Further studies are needed to determine the utility of cinacalcet in patients with spontaneous resolution of HPT or low bone turnover. This review discusses the pathophysiology of post-kidney transplant HPT, associated complications, and current options for clinical management.
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PMID:Therapeutic management of post-kidney transplant hyperparathyroidism. 2057 35


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