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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calcimimetics reduce serum levels of parathyroid hormone (PTH) and calcium, with a leftward shift in the set-point for calcium-regulated PTH secretion. The aim of this publication is to review the data available for calcimimetics in primary, secondary and tertiary hyperparathyroidism (HPT). Parathyroidectomy (PTX) is currently the only curative treatment for primary HPT, and recommended for patients with moderate-to-severe disease, as defined by a 2002 National Institute's of Health summary statement. In general, patients with primary HPT not meeting these surgical criteria, as well as those with contraindication or refusal for surgery, are monitored for signs and symptoms of primary HPT. There are currently no non-surgical therapies approved for use in primary HPT, although bisphosphonates are used in some patients, in an effort to control serum calcium levels. Calcimimetics decrease PTH and calcium levels and are a potential alternative for patients contraindicated for PTX, or who have failed previous PTX and have recurrent primary HPT. Secondary HPT develops early in chronic kidney disease and is present virtually in all patients with end-stage renal disease (ESRD). Secondary HPT is a progressive disease and is associated with several systemic complications, including renal osteodystrophy, soft tissue and vascular calcifications, and adverse cardiovascular outcomes. In ESRD patients, calcimimetics were shown to simultaneously reduce PTH, calcium, phosphate and calcium x phosphate product. In addition, observational analyses of use of calcimimetics in the ESRD population have shown a reduction of important clinical outcomes. In renal allograft recipients with tertiary HPT and hypercalcaemia, calcimimetics are a promising treatment option to control the parameters of calcium phosphate metabolism and may be a valid alternative to PTX. Based on its unique mechanism of action, the calcimimetic cinacalcet may play a role in the medical treatment of primary and tertiary forms of HPT, in addition to the registered indication for the treatment of secondary HPT.
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PMID:The role of calcimimetics in the treatment of hyperparathyroidism. 1803 25

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

Renal transplantation is the treatment of choice for patients with end-stage renal disease. It corrects most of the metabolic abnormalities that cause renal osteodystrophy. Nevertheless, renal osteodystrophy persists in many transplant recipients. The aim of this study was to investigate frequency and histomorphometric pattern of bone disease after renal transplantation. Bone biopsy specimens were taken from the iliac crest of 57 patients, including 28 women (26-70 years old) and 29 men (27-67 years old). Indications for biopsy were hypercalcemia, elevation of parathyroid hormone, and, in 19 cases, without suspected bone abnormalities based on laboratory parameters. The mean time of dialysis prior to renal transplantation was 43 months (range, 6-91 months in women and 10-111 months in men) and the mean interval between transplantation and bone biopsy was 53.5 months (range, 4-191 months in women and 5-90 months in men). Fourteen patients were treated with either 25-hydroxyvitamin D3 and/or 1-alpha hydroxyvitamin D3 or 1,25 dihydroxyvitamin D3, 3 with phosphate-binding agents. The immunosuppression consisted of cyclosporine, azathioprine, and prednisolone. The cumulative dosage of corticosteroids was 5569+/-5305 mg. For static and dynamic histomorphometry, we used American Society of Bone and Mineral Research nomenclature. Mild osteitis fibrosa and osteitis fibrosa, the most frequent forms of renal osteodystrophy, were observed in 13. (22.8%) and 14 patients (24.6%), respectively. Mixed uremic osteodystrophy was found in 7 patients (12.3%), adynamic renal bone disease in 3 patients (5.3%), and osteomalacia in 2 patients (3.5%). In 13 patients (22.8%), reduced bone mass and structural damage without typical signs of renal osteodystrophy, such as endosteal fibrosis or osteoclasia, were detected, and 5 patients (8.7%) showed normal histomorphometric parameters. We concluded that renal osteodystrophy, especially forms with high bone turnover, persisted in many patients after successful renal transplantation. This finding may be due to preexisting conditions, such as duration of dialysis and degree of hyperparathyroidism. Bone disease is increased by corticosteroid and immunosuppressive therapy after renal transplantation and requires close monitoring.
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PMID:Renal osteodystrophy after successful renal transplantation: a histomorphometric analysis in 57 patients. 1808 42

Hemodialysis (HD) patients are commonly affected by secondary hyperparathyroidism (SHPT), in which 3 well-known factors are usually involved: hypocalcemia, hyperphosphatemia and calcitriol deficiency. Classically, high parathyroid hormone (PTH) levels cause bone-associated diseases, such as osteitis fibrosa and renal osteodystrophy, but more recently it has been demonstrated the link between SHPT and a systemic toxicity, with a major role in determining cardio-vascular disease, including arterial calcification, endocrine disturbances, compromised immune system, neurobehavioral changes, and altered erythropoiesis. Treatment with calcitriol (CT), the active form of vitamin D, reduces parathyroid hormone (PTH) levels, but may result in elevations in serum calcium (Ca) and phosphorus (P), increasing the risk of cardio-vascular calcification in the HD population. Several new vitamin D analogs have been developed and investigated with the rationale to treat SHPT with a reduced risk of hypercalcemia and hyperphosphatemia in HD patients. Paricalcitol (1,25-dihydroxy-19-nor-vitamin D(2), 19-Nor-D(2)) is a vitamin D analog that suppresses PTH secretion with minimal increases on serum calcium and phosphate levels. It was demonstrated that paricalcitol prevents vascular calcification in experimental models of renal failure, compared with calcitriol. Furthermore, 19-Nor-D(2) is the first analog approved for use in HD patients and is available for i.v. and oral administration, commonly 3 times weekly after HD. The purpose of the present review is to analyze the pathogenesis and treatment of SHPT in HD patients, and the role of paricalcitol in the prevention of arterial calcification.
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PMID:Pathogenesis and treatment of secondary hyperparathyroidism in dialysis patients: the role of paricalcitol. 1839 17

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

Renal osteodystrophy is characterized by abnormalities in bone turnover, mineralization, and bone volume. The effects of treatment modalities for renal osteodystrophy on bone should be analyzed with respect to these abnormalities. The major treatment modalities for renal osteodystrophy include phosphate binders, vitamin D compounds, and calcimimetics. Aluminum-containing phosphate binders have been shown to be toxic to bone secondary to their effects on bone turnover, mineralization, and bone volume. The use of calcium-based phosphate binders has been associated with the development of adynamic bone disease (low bone turnover), bone loss, and worsening of vascular calcifications. New nonaluminum, noncalcium phosphate binders have been developed (sevelamer hydrochloride and lanthanum carbonate). These agents show a potential for improvement in bone turnover and bone volume. Patients with renal osteodystrophy are deficient in calcitriol and often in calcidiol. Calcidiol deficiency has been underappreciated and deserves to be addressed in the treatment of patients with renal osteodystrophy. Calcitriol replacement therapy by daily oral administration is associated with frequent episodes of hypercalcemia and suppression of bone turnover in patients with stages 3 to 5 chronic kidney disease. Pulse oral or intravenous calcitriol administration induces frequent episodes of hypercalcemia or hyperphosphatemia, respectively, and achieves the same degree of correction of bone abnormalities. There are no data on the effects of paricalcitol or doxercalciferol on human bone. Experimental data, however, show that these two analogues and maxacalcitol may control serum parathyroid hormone levels without suppressing bone turnover. Calcimimetics lower parathyroid hormone levels and bone turnover.
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PMID:Effects of treatment of renal osteodystrophy on bone histology. 1898 1

Over the past almost 50 years several calcium concentrations in the dialysate (CaD) have been used to balance calcium in hemodialysis (HD) patients but a consensus as to which is most appropriate has not been established. Moreover, since the late 1980s, further confusion has been caused following the use of calcium salts as intestinal phosphate binders. This paper reports results of 387 chronic HD patients with respect to secondary hyperparathyroidism (sHPT) and renal osteodystrophy (ROD) of a single center over 20 years. The most important therapeutic measures applied were use of only 2 CaD, 1.5 and 1.75 mmol/l, with very few exceptions, administration of either calcium-containing or calcium-magnesium-containing and/or calcium-free phosphate binders, no dietary restrictions and continuous compensation of uremic acidosis via dialysate and oral supplements of bicarbonate. Using one of the two CaD and selective administration of different phosphate binders for fine adjustment of serum calcium through this combination, we were able to maintain in the long term almost physiological conditions. With exception of the phosphate metabolism, most physiological functions with regard to sHPT and ROD returned close to normal. As a result, the incidence of hypercalcemia, hypocalcemia, extraosseous, extravascular calcification, bone pain and spontaneous bone fractures was extremely low. We conclude that the clinical advantages of the therapeutic measures, above all precise balance of calcium homeostasis, in our investigation were demonstrated by high survival rates (92% after the first year on HD, 82% after 2, and 55% after 5 years), low incidence of cardiovascular fatalities (about 25%), and very low incidence of sHPT (mostly normal parathyroid hormone levels, 1 parathyrdoidectomy within 20 years).
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PMID:Use of two calcium concentrations in hemodialysis--report of a 20-year clinical experience. 1928 40

Graft and patient survival in renal transplantation has increased with better immune suppression treatment, leading to the appearance of new complications such as posttransplant bone disease. After renal transplantation and the recovery of renal function, mineral metabolism disorders secondary to renal failure could be expected to normalize. However, both immediately after transplantation and later, and even with good renal graft function, we see bone disorders associated to renal osteodystrophy, a high incidence of osteopenia, persistent hyperparathyroidism, hypercalcemia, hypophosphoremia, and less commonly, aseptic bone necrosis. The causes potentially responsible for these disorders have basically been identified as different degrees of renal insufficiency in the graft, persistent posttransplant secondary hyperparathyroidism, and negative impact of immunosuppression treatment, particularly corticosteroids. The most important factor in the evolution of metabolic and bone disorders after renal transplantation, however, is pretransplant bone status. Special attention should be paid to other osteoarticular complications such as loss of bone mass and fractures, leading to significant morbidity. In the therapeutic approach to these patients, as well as encouraging physical exercise and advice about diet or other habits, the use of drugs such as calcium and vitamin D supplements, bisphosphonates, and more recently, calcimimetics have made significant improvements in the prevention and treatment of bone-mineral metabolism. It has been shown that calcimimetic agents can control the parathyroid hormone, reduce episodes of hypercalcemia, and improve hypophosphatemia. Their properties have to be assessed in broader studies to establish the basis for their widespread use among renal transplant recipients.
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PMID:Treatment with calcimimetics in kidney transplantation. 2030 56

Abnormal mineral metabolism and altered bone structure and composition occur early in the course of chronic kidney disease. We present difficulties in renal osteodystrophy treatment in patient undergoing renal replacement therapy for twenty two years (dialysis, transplant, dialysis), which is not in the waiting list for kidney transplant (patient disagreement). Due to failure of conventional therapy of hyperparathyroidism (calcium, phosphate binders, vitamin D) he was needed parathyroidectomy twice. Now he presents a very low PTH level but hyperphosphatemia, hypercalcemia and calcium/phosphate product over upper limit. This disturbances led to extra skeletal calcification (skin, vessels, eyes - "red eyes syndrome", central nervous system). Even now having new phosphate binders we cannot keep plasma phosphate, calcium in normal range, probably due to inadequate diet and non-compliance. Effective therapy is still difficult in this patient.
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PMID:[Difficulties in renal osteodystrophy treatment in patient undergoing long-term renal replacement therapy--a case study]. 2036 25

Renal transplantation is the definitive treatment for many metabolic abnormalities of uremic patients, although it is only partially effective for renal osteodystrophy, which may interact with posttransplant renal osteopathy. Osteopenic-osteoporotic syndrome represents, together with fractures secondary to osteoporosis and osteonecrosis, the bone complication most related to renal transplantation. Several factors contribute to the pathogenesis of posttransplantation osteoporosis, particularly immunosuppressive treatment. In this study, we evaluated the prevalence of factors related to posttransplant renal osteopathy and the clinical impact of immunosuppressive protocols. We studied 24 renal transplant recipients with hypercalcemia. Glomerular filtration rate was >50 mL/min. Mean age, time on dialysis, and time from transplantation were 49.6, 5.4, and 6.9 years, respectively. We evaluated serum and urine calcium and phosphorus, calcitonin, parathormone, bone-specific alkaline phosphatase, osteocalcin, urine deoxypyridinoline, telopeptide of type 1 procollagen, 1,25-(OH)(2) and 25-OH vitamin D, parathyroid ultrasound, and computerized bone mineralometry. The combination of sirolimus and steroids resulted in the most disadvantageous outcomes regarding alkaline phosphatase and mineralometry. Calcineurin inhibitors did not significantly influence bone metabolism markers; mycophenolate mofetil evidenced no effect on bone. According to the literature, steroids account for the abnormalities found in our patients and in severe osteopenia. Several factors may contribute to the development of osteoporosis and fractures in transplantation patients, although they are overcome by the prominent effect of steroids. In patients at high risk of osteoporosis, steroid-free therapy should be considered. Everolimus is indicated for diseases with bone loss. Combined therapy with everolimus and mycophenolic acid without cyclosporine and steroids, seemed to be particularly indicated. Prophylactic treatments should be commenced early. No single marker was useful to diagnose posttransplant renal osteopathy. The definitive diagnosis should be made by bone biopsy during transplantation, and noninvasive procedures, such as densitometry and evaluation of biologic markers, may be useful during follow-up.
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PMID:Immunosuppressive agents and bone disease in renal transplant patients with hypercalcemia. 2053 47


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