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)

Pathogenesis of vascular calcification in chronic kidney disease. Background. Hyperphosphatemia and hypercalcemia are independent risk factors for higher incidence of cardiovascular events in patients with chronic kidney disease. In addition to increased calcium-phosphate product, hyperphosphatemia accelerates the progression of secondary hyperparathyroidism with the concomitant bone loss, possibly linked to vascular calcium-phosphate precipitation. Results. The control of serum phosphate levels reduces vascular calcification not only by decreasing the degree of secondary hyperparathyroidism and calcium-phosphate product, but also by reducing the expression of proteins responsible for active bone mineral deposition in cells of the vasculature. The calcium and aluminum-free phosphate-binders provide a new and effective therapeutic tool in preventing vascular calcifications in chronic kidney disease in animal models and in hemodialysis patients. Conclusion. Additional investigations are necessary to examine the benefits of different phosphate-binders in reducing mortality from cardiovascular disease.
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PMID:Pathogenesis of vascular calcification in chronic kidney disease. 1637 46

Activated vitamin D continues to be the major treatment for suppressing parathyroid hormone (PTH) levels in dialysis patients who have secondary hyperparathyroidism. Active vitamin D compounds are distinguished by their ability to bind with high affinity to vitamin D receptors (VDRs) not only in the parathyroid glands, but in cells throughout the body. Because of recent data showing that pulsatile, intravenous vitamin D treatment (calcitriol or paricalcitol) confers a survival advantage in the dialysis population, there is new interest in understanding the systemic effects of VDR activation, particularly in the predialysis stages of chronic kidney disease (CKD), where high mortality rates from cardiovascular disease have recently been documented. Previous underutilization of calcitriol treatment to control PTH levels in stages 3 and 4 CKD was often due to concerns about its potential for accelerating the progression of CKD as a consequence of hypercalcemia, hypercalciuria, or hyperphosphatemia. Vitamin D analogs with selective VDR activity (such as paricalcitol) have great potential for preventing parathyroid hyperplasia and bone loss in early CKD without adversely affecting kidney function. Whether they also reduce cardiovascular morbidity and mortality in early CKD, as they appear to do in dialysis patients, remains to be determined.
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PMID:Vitamin D treatment in chronic kidney disease. 1607 55

Childhood renal osteodystrophy (ROD) is the consequence of disturbances of the calcium-regulating hormones vitamin D and parathyroid hormone (PTH) as well as of the somatotroph hormone axis associated with local modulation of bone and growth cartilage function. The resulting growth retardation and the potentially rapid onset of ROD in children are different from ROD in adults. The biochemical changes of ROD as well as its prevention and treatment affect calcium and phosphorus homeostasis and are directly associated with the development of cardiovascular disease in pediatric renal patients. The aims of the clinical and biochemical surveillance of pediatric patients with CRF or on dialysis are prevention of hyperphosphatemia, avoidance of hypercalcemia and keeping the calcium phosphorus product below 5 mmol(2)/l(2). The PTH levels should be within the normal range in chronic renal failure (CRF) and up to 2-3 times the upper limit of normal levels in dialysed children. Prevention of ROD is expected to result in improved growth and less vascular calcification.
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PMID:Prevention and treatment of renal osteodystrophy in children on chronic renal failure: European guidelines. 1624 44

Cardiovascular disease and stroke account for 60-70% of all deaths in patients with end-stage renal disease (ESRD), at a risk that is 10-20-fold the age- and sex-matched general population. There is also increased coronary artery calcification and increased cardiovascular mortality in chronic kidney disease (CKD) and dialysis patients compared with the general population. Bone is similarly abnormal in CKD. There is an increased incidence of low bone mass and fractures in dialysis patients compared with the general population. Furthermore, a hip fracture in a dialysis patient is associated with a doubling of the mortality observed in nondialysis patients with a hip fracture. These two problems may be linked, as cross-sectional studies have demonstrated an inverse relationship between osteoporosis and coronary artery calcification in the general population and in ESRD patients. In vitro and ex vivo, there is clear evidence that vascular calcification is an active cell-mediated process, made worse by disorders of mineral metabolism. Many factors known to be associated with cardiovascular disease in CKD patients can directly increase calcification in vitro. In addition, in CKD, there are many mechanisms by which bone may adversely affect vascular calcification including disorders of bone remodelling, altered secretion of parathyroid hormone (PTH), hyperphosphatemia, hypercalcaemia, use of calcium based binders, and excessive vitamin D therapy. The coexistence of vascular risk factors and abnormal bone represent a double threat to the well being of patients with CKD.
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PMID:Vascular calcification and renal osteodystrophy relationship in chronic kidney disease. 1688 98

Secondary hyperparathyroidism (SHPT) leads not only to bone disorders, but also to cardiovascular complications in long-term dialysis patients. Conventional treatment with calcium (Ca) supplement, phosphate (P) binders and active vitamin D analogs lead in part to amelioration of SHPT, but are simultaneously associated with unacceptable side-effects, including hypercalcemia, hyperphosphatemia, and increased Ca x P products, which are the risk factors for cardiovascular disease in dialysis patients. Conventional treatment has been unable to facilitate the attainment of optimal management of SHPT proposed in the K/DOQI guidelines. Cinacalcet HCl (cinacalcet), a novel calcimimetic compound, restores the sensitivity of the Ca-sensing receptor in parathyroid cells, and decreases serum parathyroid hormone (PTH) without introducing hypercalcemia or hyperphosphatemia. Cinacalcet treatment enables a significant number of patients to achieve the K/DOQI guideline. Based on experimental data, calcimimetics could ameliorate cardiovascular calcification and remodeling in uremic rats with SHPT. Clinical trials have shown that cinacalcet significantly reduced the risks of parathyroidectomy, fracture and cardiovascular hospitalization among long-term dialysis patients with SHPT. Parathyroid intervention therapy (parathyroidectomy and percutaneous direct injection) is also a useful alternative. In the present article, we review novel therapeutic strategies for SHPT.
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PMID:Therapeutic strategies for secondary hyperparathyroidism in dialysis patients. 1691 Nov 89

The dialysate calcium (Ca) concentration for hemodialysis (HD) patients can be adjusted to manage more optimally the body's Ca and phosphate balance, and thus improve bone metabolism as well as reduce accelerated arteriosclerosis and cardiovascular mortality. The appropriate dialysate Ca concentration allowing this balance should be prescribed to each individual patient depending on a multitude of variable factors relating to Ca load. A lower dialysate Ca concentration of 1.25 to 1.3 mmol/L will permit the use of vitamin D supplements and Ca-based phosphate binders in clinical practice, with much less risk of Ca loading and resultant hypercalcemia and calcification. Low Ca baths are useful in the setting of adynamic bone disease where an increase in bone turnover is required. However, low Ca levels in the dialysate may also predispose to cardiac arrhythmias and hemodynamically unstable dialysis sessions with intradialytic hypotension. Higher Ca dialysate is useful to sustain normal serum Ca levels where patients are not taking Ca-based binders or if Ca supplements are not able to normalize serum levels. Suppression of hyperparathyroidism is also effective with dialysate Ca of 1.75 mmol/L, but hypercalcemia, metastatic calcification, and oversuppression of parathyroid hormone are risks. Dialysate Ca of 1.5 mmol/L may be a compromise between bone protection and reduction in cardiovascular risk for conventional HD and is a common concentration used throughout the world. The increase in longer, more frequent dialysis such as short-daily and nocturnal HD, however, provides another challenge with regard to optimal dialysate Ca levels and higher levels of 1.75 mmol/L are probably indicated in this setting. Difficulties in determining the ideal dialysate Ca occur because of the complex pathophysiology of bone and mineral metabolism in HD patients and there needs to be a balance between dialysis prescription and other treatment modalities. To optimize management of the abnormal Ca balance, other aspects of this disorder need to be more fully clarified and, with evolving medications for phosphate control and treatment of secondary hyperparathyroidism, as well as the emergence of a multitude of different HD regimes, further studies are required to make definitive recommendations. At present, we need to maintain flexibility with HD treatments and so dialysate Ca needs to be individualized to meet the specific requirements of patients by optimizing management of renal bone disease and simultaneously reducing metastatic calcification and cardiovascular disease.
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PMID:Review of dialysate calcium concentration in hemodialysis. 1701 7

Secondary hyperparathyroidism (SHPT) is a common and serious consequence of chronic kidney disease (CKD). SHPT is a complex condition characterised by a decline in 1,25-dihydroxyvitamin D and consequent vitamin D receptor (VDR) activation, abnormalities in serum calcium and phosphorus levels, parathyroid gland hyperplasia, elevated parathyroid hormone (PTH) secretion, and systemic mineral and bone abnormalities. There are three classes of drugs used for treatment of SHPT: (i) nonselective VDR activators or agonists (VDRAs); (ii) selective VDRAs; and (iii) calcimimetics. The VDRAs act on the VDR, whereas the calcimimetics act on the calcium-sensing receptor. Calcimimetics are commonly used in conjunction with VDRA therapy. By virtue of the differences in their chemical structure, the nonselective and selective VDRAs differ in their effects on gene expression, and ultimately parathyroid gland, bone and intestine function. Medications in all three classes are effective in suppression of PTH; however, clinical studies show that calcimimetics are associated with an unfavourable tolerability profile and hypocalcaemia, whereas nonselective VDRAs, and to a lesser extent selective VDRAs, are associated with dose-limiting hypercalcaemia and hyperphosphataemia. Selective VDRAs also have minimal undesirable effects on calcium absorption in the intestine, and calcium and phosphorus mobilisation in the bone compared with nonselective VDRAs. Calcium load in patients with CKD can lead to vascular calcification, accelerated progression of cardiovascular disease and increased mortality. High serum phosphorus levels are also associated with adverse effects on cardiorenal function and survival. Recent evidence suggests that VDRAs are associated with a survival benefit in CKD patients, with a more favourable effect with selective VDRAs than nonselective VDRAs. Paricalcitol, a selective VDRA, is reported to exert specific effects on gene expression in various cell types that are involved in vascular calcification and the development of coronary artery disease. This article examines the molecular mechanisms that determine selectivity of VDRAs, and reviews the evidence for clinical efficacy, safety and survival associated with the three drug classes used for treatment of SHPT in CKD patients.
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PMID:Vitamin D receptor activator selectivity in the treatment of secondary hyperparathyroidism: understanding the differences among therapies. 1788 83

Abnormal bone in chronic kidney disease (CKD) may adversely affect vascular calcification via disordered calcium and phosphate metabolism. In this context, bone health should be viewed as a prerequisite for the successful prevention/treatment of vascular calcification (VC) along with controlled parathyroid hormone (PTH) secretion, the use of calcium-based phosphate binders and vitamin D therapy. In CKD patients, VC occurs more frequently and progresses more rapidly than in the general population, and is associated with increased cardiovascular disease (CVD) morbidity and mortality. A number of therapies aimed at reducing PTH concentration are associated with an increase of calcaemia and Ca x P product, e.g. calcium-containing phosphate binders or active vitamin D. The introduction of calcium-free phosphate binders has reduced calcium load, attenuating VC and improving trabecular bone content. In addition, a major breakthrough has been achieved through the use of calcimimetics, as first agents which lower PTH without increasing the concentrations of serum calcium and phosphate. Nowadays, it is becoming evident that even early stage CKD is recognised as an independent CVD risk factor. Moreover, the excess of CVD among dialysis patients cannot be explained entirely on the basis of abnormal mineral and bone metabolism. Hence, much controversy has surrounded the cost-effectiveness of treatment with the new phosphate-binding drugs as well as new vitamin D analogs and calcimimetics. Thus, it seems prudent and reasonable that maintaining bone health and mineral homeostasis should rely on some modifications of standard phosphate binding and calcitriol therapy. Hypophosphataemia and hypercalcaemia in adynamic bone disease (ABD) might be treated by reducing the number of calcium carbonate/acetate tablets in order to increase serum phosphate and decrease serum calcium, which, in turn, might positively stimulate PTH secretion. The same rationale is assumed for the use of a low calcium dialysate. On the other hand, secondary hyperparathyroidism with hyperphosphataemia and hypocalcaemia should be treated with a substantial number of calcium carbonate/acetate tablets in combination with calcitriol and low calcium dialysate in order to decrease serum phosphate and maintain the Ca x P product within K/DOQI guidelines (<4.4 mmol l(-1)). Finally, it becomes apparent that prevention, with judicious use of calcium-based binders, vitamin D and a low calcium dialysate without adverse effects on Ca x P or oversuppression of PTH, provides the best management of VC and mineral and bone disorder in CKD patients.
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PMID:Bone health and vascular calcification relationships in chronic kidney disease. 1789 31

Childhood and adolescence are crucial times for the development of a healthy skeletal and cardiovascular system. Disordered mineral and bone metabolism accompany chronic kidney disease (CKD) and present significant obstacles to optimal bone strength, final adult height, and cardiovascular health. Decreased activity of renal 1 alpha hydroxylase results in decreased intestinal calcium absorption, increased serum parathyroid hormone levels, and high-turnover renal osteodystrophy, with subsequent growth failure. Simultaneously, phosphorus retention exacerbates secondary hyperparathyroidism, and elevated levels contribute to cardiovascular disease. Treatment of hyperphosphatemia and secondary hyperparathyroidism improves growth and high-turnover bone disease. However, target ranges for serum calcium, phosphorus, and parathyroid hormone (PTH) levels vary according to stage of CKD. Since over-treatment may result in adynamic bone disease, growth failure, hypercalcemia, and progression of cardiovascular calcifications, therapy must be carefully adjusted to maintain optimal serum biochemical parameters according to stage of CKD. Newer therapeutic agents, including calcium-free phosphate binding agents and new vitamin D analogues, effectively suppress serum PTH levels while limiting intestinal calcium absorption and may provide future therapeutic alternatives for children with CKD.
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PMID:Chronic kidney disease mineral and bone disorder in children. 1804 81

Dietary reference intakes (DRIs) for Vitamin D (VitD) have been traditionally established based on plasma 25-OHD concentration sufficient to prevent rickets and osteomalacia. While nutritional rickets is still prevalent in developing countries, hypovitaminosis D is becoming widespread around the world regardless the latitude. Emerging evidence has unravelled the physiological roles of VitD beyond calcium homeostasis. Hypovitaminosis D has been linked to cancers, diabetes, CVD, periodontal diseases and influenza. Hypovitaminosis D is multifactorial and is related to VitD scarcity in foods, latitude, solar-irradiation, atmospheric-pollution, skin-pigmentation, clothing, sunscreen-use and indoor activities, etc. Plasma 25-OHD concentration range from 25-138 nmol/L. A higher plasma 25-OHD concentration is linked to higher bone-mass in adolescents, pre- and post-menopausal women. Plasma 25-OHD > or =75 nmol/L has been shown to enhance calcium absorption, suppress PTH elevation, reduce the risks of bone loss and fractures, and certain extra-skeletal diseases. VitD supplementation with 10 microg/d is insufficient to lower fracture risks. Combined VitD and calcium supplementation in higher doses has been found superior to VitD alone to increase bone-mass in adolescents and to reduce non-vertebral fractures in postmenopausal women. In future, DRIs for VitD are likely to be established beyond its skeletal roles to include multiple health outcomes. However, the desirable level of VitD has yet to be defined. Furthermore, redefining the upper-tolerable-level of VitD intake is necessary to prevent hypercalcemia and toxicity. There is also a urgent need to harmonize laboratory methods in VitD assay in different laboratories.
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PMID:The resurgence of the importance of vitamin D in bone health. 1829 22


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