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)

Secondary hyperparathyroidism (SHPT) remains a treatment dilemma in pediatric dialysis patients. Recent experience with paricalcitol (P), a vitamin D analogue, in adults with SHPT has shown equal efficacy and improved survival compared to traditional treatment with calcitriol (C). We present our experience with (C) compared to (P) treatment in our pediatric dialysis patients with SHPT. Twenty-one patients (mean age 11.5+/-5 years) with SHPT (intact parathyroid hormone (iPTH) averaging 1,228+/-496 pg/ml) were studied. Seventeen received (C) followed by (P); while an additional four were treated with either (C=1) or (P=3) alone. After 26+/-8 weeks, average percent (%) decrease in iPTH was similar with (C) and (P) (-60.4+/-34% versus -65.4+/-28%, respectively; p=0.6). In the (P) group, the effective dose in children was greater than in adult trials based on kilogram weight. Episodes of hypercalcemia between the treatment groups were not different. However, episodes of elevated calcium x phosphorus product (CaxP)> or =70 mg(2)/dl(2) occurred more frequently in the (C) group (odds ratio=1.5; p=0.01). Paricalcitol appears to be safe and effective in pediatric patients. Data suggest that dosing should be gauged according to degree of SHPT. This should serve as impetus for future pharmacokinetic studies in pediatric dialysis patients.
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PMID:Paricalcitol versus calcitriol treatment for hyperparathyroidism in pediatric hemodialysis patients. 1690 Mar 83

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

Although approximately half of patients undergoing hemodialysis receive activated forms of Vitamin D, the primary reason to initiate this therapy has rested solely on the management of secondary hyperparathyroidism. Secondary hyperparathyroidism is likely one of several consequences of Vitamin D deficiency, and only now have other consequences of Vitamin D deficiency emerged. Although previously viewed as a contributor to hypercalcemia and hyperphosphatemia, recent studies suggest Vitamin D may improve cardiovascular structure and function, improve vascular compliance, and reduce pro-inflammatory cytokines, all of which may contribute to the improved survival observed in retrospective studies examining the outcome of patients treated with activated Vitamin D compared to those who were not. The current review examines two recent large-scale studies of hemodialysis patients: one that demonstrated a survival advantage of paricalcitol over calcitriol, and a second that demonstrated a significant survival advantage of any intravenous Vitamin D formulation versus none. In both studies, the findings were independent of mineral and parathyroid hormone levels, suggesting "non-traditional" actions of Vitamin D contributed to the observed survival advantage. Potential steps moving forward in light of these observational studies are subsequently discussed.
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PMID:Vitamin D in patients with renal failure: a summary of observational mortality studies and steps moving forward. 1719 69

Secondary hyperparathyroidism commonly develops in patients with chronic kidney disease (CKD) in response to high phosphate, low calcium and low 1alpha,25-dihydroxyvitamin D(3) (calcitriol) levels. High levels of parathyroid hormone (PTH) accelerate bone turnover, with efflux of calcium and phosphate that can lead to vascular calcification. Treatment of secondary hyperparathyroidism with calcitriol and calcium-based phosphate binders can produce hypercalcemia and oversuppression of PTH, which results in adynamic bone that cannot buffer calcium and phosphate levels, and increased risk of vascular calcification. PTH levels must, therefore, be reduced to within a range that supports normal bone turnover and minimizes ectopic calcification. Vitamin D analogs that inhibit PTH gene transcription and parathyroid hyperplasia (and have reduced calcemic activity) are a safer treatment for secondary hyperparathyroidism than calcitriol; these agents enhance the survival of patients with CKD. Several such analogs are now in use, and analogs with even greater selectivity than those currently used are in development. Parathyroid glands express both 25-hydroxylase and 1alpha-hydroxylase, which suggests that these enzymes might suppress parathyroid function by an autocrine mechanism. The risk of hypercalcemia with vitamin D analog therapy is reduced by the introduction of non-calcium-based phosphate binders and cinacalcet; furthermore, recent trials indicate that early intervention with vitamin D analogs in stage 3 and 4 CKD can correct PTH levels, and could prevent renal bone disease and prolong patient survival.
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PMID:Drug insight: vitamin D analogs in the treatment of secondary hyperparathyroidism in patients with chronic kidney disease. 1723 40

Secondary hyperparathyroidism (2 degrees HPT) commonly develops in patients with chronic kidney disease (CKD) in response to high phosphate, low calcium and low 1,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)]. High PTH levels increase the rate of bone turnover, with a net efflux of calcium and phosphate leading to vascular calcification and coronary artery disease. Treatment of 2 degrees HPT with 1alpha,25(OH)(2)D(3) and calcium-based phosphate binders often produces hypercalcemia and over-suppression of PTH, resulting in adynamic bone that cannot buffer excess calcium and phosphate, which increases the risk of vascular calcification. It is essential, then, to reduce PTH levels to a range that supports normal bone turnover and minimizes ectopic calcification. Vitamin D analogs that inhibit PTH gene transcription and parathyroid hyperplasia, and that have less calcemic activity than 1alpha,25(OH)(2)D(3,) have provided a greater safety margin for the treatment of 2 degrees HPT, as well as enhancing the survival of CKD patients. Although several analogs with less calcemic activity are now used in patients (paricalcitol and doxercalciferol in the USA, and OCT and falecalcitriol in Japan), efforts to develop even more selective analogs continue. Parathyroid glands express both 25-hydroxylase and 1alpha-hydroxylase and may be capable of activating prohormones or prodrugs to suppress PTH and parathyroid growth by an autocrine mechanism. Moreover, the introduction of non-calcium-based phosphate binders (sevelamer and lanthanum carbonate) and cinacalcet (an allosteric activator of the calcium receptor that reduces PTH and the serum calciumxphosphate product) may reduce the risk of hypercalcemia with vitamin D therapy. Combining these agents with higher doses of vitamin D compounds may achieve greater suppression of PTH and possibly enhance survival in patients with chronic kidney disease.
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PMID:Vitamin D analogs for secondary hyperparathyroidism: what does the future hold? 1736 85

Secondary hyperparathyroidism (SHPT) is one of mineral bone disorders in chronic kidney disease (CKD) , when stage of SHPT become advance, not only responsiveness for drug will be decreased, but also serum parathyroid hormone (PTH), calcium (Ca) , and Pi level become also aggravate. Such a clinical condition is called resistance to medical treatment, and if intact PTH level is over than 500 pg/mL or there is at least one parathyroid grand more than 0.5 cm(3) in size, it is strongly suspected that SHPT becomes advance with resistance to medical treatment. Moreover, hypercalcemia and hyperphosphataemia have also been associated with reduced life expectancy, parathyroid intervention is the treatment choice for SHPT in behalf of medical therapy. Parathyroid intervention has better be chosen when there is resistant to medical treatment, even though intact PTH level is less than 500 pg/mL. Parathyroidectomy is desirable from the long term effect if more than two numbers of glands are detected by ultrasonography. Parathyroid intervention is chosen depending on the degree of SHPT and presence of some complications, and it should be perform in the appropriate period.
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PMID:[Indication of parathyroid intervention]. 1747 Oct 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

Secondary hyperparathyroidism has a significant impact on morbidity and mortality due to skeletal and extraskeletal manifestations. Cinacalcet, a newly developed calcimimetic, is reported to decrease parathyroidism, as well as serum levels of phosphorus (P) and calcium (Ca) and therefore Ca x P product. Available evidence has shown that cinacalcet decreases the rate of parathyroidectomy and bone fracture in hemodialysis patients, but the death rate remains the same. Although, it is not yet available in Japan, cinacalcet is expected to be available as a possible drug for patients undergoing hemodialysis due to secondary hyperparathyroidism associated with refractory hyperphosphatemia and hypercalcemia. Except for the high cost, cinacalcet will be a welcome therapeutic option for end-stage renal disease and probably also for pre-end-stage renal disease patients. Dietary phosphate restriction and adequate hemodialysis, however, are still the main strategy for the control of hyperphosphatemia and secondary hyperparathyroidism.
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PMID:Pharmacological control of secondary hyperparathyroidism in chronic hemodialysis patients: cinacalcet is coming to Japan. 1831 61

Secondary hyperparathyroidism (sHPT) is a frequent complication in patients with chronic kidney disease (CKD) and a known contributor to the development of vascular calcification and renal osteodystrophy (CKD-BMD). Secondary hyperparathyroidism is also related to increased cardiovascular mortality in CKD patients. With the discovery that molecules can modulate the calcium-sensing receptor (CaR) of the parathyroid gland, new treatment options are now available to control sHPT. Calcimimetics activate the CaR and-by increasing its sensitivity to calcium-can effectively decrease parathyroid hormone (PTH) secretion. Calcimimetic treatment with cinacalcet has resulted in an effective lowering of PTH levels in both animal and clinical studies. Most clinical studies have been performed in dialysis patients, and only a few studies have been carried out in patients with CKD stage 3 & 4 and renal transplant patients. In haemodialysis patients with sHPT, cinacalcet treatment could increase the number of patients achieving National Kidney Foundation Kidney Disease Outcomes Quality Initiative targets (PTH, calcium, phosphate) compared to standard therapy. In stage 3 and 4 CKD patients, cinacalcet has been reported to reduce PTH levels, however, at the expense of increasing phosphate serum levels. Several small studies have reported that calcimimetics reduced PTH levels and hypercalcaemia after renal transplantation. In addition, two studies on paediatric dialysis patients with sHPT reported effective PTH lowering. This review summarizes recent clinical studies with cinacalcet treatment in CKD patients.
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PMID:Calcimimetics in CKD-results from recent clinical studies. 1859 67

Secondary hyperparathyroidism and the associated metabolic abnormalities are common complications of chronic kidney disease. When these disorders cannot be managed by conventional measures, including phosphate restriction, phosphate binders, vitamin D therapy, and calcimimetics, tertiary hyperparathyroidism and the associated metabolic abnormalities may develop. In such cases parathyroidectomy is required. We report a case in which a patient with tertiary hyperparathyroidism and refractory hypercalcemia who was not a surgical candidate was managed with the bisphosphonate pamidronate. This patient had failed conventional measures to manage hypercalcemia and presented with mental status changes. Pamidronate therapy was associated with a sustained decrease in serum calcium concentration and improvement in clinical symptoms. This is the first case, to our knowledge, in which pamidronate was used in a patient refractory to all other reasonable medical management, including calcimimetics.
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PMID:Hypercalcemia associated with tertiary hyperparathyroidism managed conservatively with pamidronate in a hemodialysis patient. 1936 80


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