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 (2HPT) is characterized by an abnormal threshold for suppression of parathyroid hormone (PTH) secretion by serum ionized Ca (ICa). It is therefore critical to examine the threshold of PTH secretion in chronic renal failure patients in relation to the physiopathological conditions and the severity of 2HPT. The effect of 1,25-dihidroxy-22-oxavitamin D(3) (22-oxacalcitriol, OCT) on parathyroid gland function was investigated in six haemodialysis patients with 2HPT. OCT was administered three times a week for 26 consecutive weeks. The maximum serum PTH (PTHmax), the minimum serum PTH (PTHmin), and ICa concentration required to inhibit 50% of PTHmax were estimated based on the model formula of the sigmoid curve describing the relationship between ICa and intact-PTH levels. The sigmoid ICa-PTH curves displayed a downward shift at 12 and 26 weeks of OCT treatment. Parathyroid gland function, as reflected by both PTHmax and PTHmin, decreased over time. A steep slope was found at 12 and 26 weeks, compared with that at the start of OCT treatment. There were no marked changes in the set point of calcium. Hypercalcaemia and elevated creatine phosphokinase, probably due to OCT therapy, were observed during the study period. In view of the findings that the sigmoid ICa-PTH curve displayed a downward shift, that both PTHmax and PTHmin decreased, and that functional mass of the parathyroid gland was reduced, OCT appears to be useful in ameliorating parathyroid gland function, contributing to the management of 2HPT.
Nephrol Dial Transplant 2002
PMID:Effects of 1,25-dihydroxy-22-oxavitamin D(3) on parathyroid gland function in haemodialysis patients with secondary hyperparathyroidism. 1238 65

A trial on the long-term administration of 1,25-dihydroxy-22-oxavitamin D(3) (22-oxacalcitoriol, OCT) was conducted among 124 patients with chronic renal failure on maintenance haemodialysis (HD) complicated with secondary hyperparathyroidism (2HPT). In the trial, OCT was administered three times weekly for 26 weeks subsequent to a 26-week pre-trial. As a result, intact-parathyroid hormone (PTH) levels fell significantly after the start of administration and, at the end of the trial, PTH was decreased by over 30% in 51.6% (64/124) of the patients, and the levels of bone metabolism markers such as alkaline phosphatase (ALP), bone ALP, and tartrate-resistant acid phosphatase (TRACP) were significantly decreased compared with those at the start of administration, suggesting a correction of high-turnover bone disease. Serum calcium (Ca) levels rose significantly following OCT administration, but were successfully maintained within a physiological level. Hypercalcaemia, which was diagnosed in 33.1% of patients, was found to resolve or ameliorate immediately after the withdrawal or dose reduction of OCT. OCT can be administered for as long as 1 year without any major problems other than hypercalcaemia. The final doses ranged from 2.5 to 20.0 microg/HD, and the optimal dose varied among patients depending on the intact-PTH and adjusted serum Ca levels. These results suggest that OCT is a highly effective drug for the suppression of PTH levels in 2HPT, and is an overall safe drug if the dosage is adjusted for serum Ca and intact-PTH levels. This study confirmed that the long-term (1-year) administration of OCT is very useful for the treatment of 2HPT.
Nephrol Dial Transplant 2002
PMID:Long-term effect of 1,25-dihydroxy-22-oxavitamin D(3) on secondary hyperparathyroidism in haemodialysis patients. One-year administration study. 1238 66

Abnormalities in calcium and phosphorus metabolism are common, and metabolic bone disease develops often in patients with chronic renal failure (CRF). Effective clinical management includes measures to control phosphorus retention and prevent hyperphosphataemia, to maintain serum calcium concentrations within the normal range and to prevent excess parathyroid hormone (PTH) secretion by the judicious use of vitamin D sterols. Certain of these interventions appear to increase the risk of soft tissue and vascular calcification in patients with end-stage renal disease (ESRD), changes that may contribute to the development of cardiovascular disease. Current therapeutic approaches are thus being re-evaluated in an effort to limit these risks. Despite the importance of controlling phosphorus retention and preventing hyperphosphataemia in patients with CRF, current management strategies often are inadequate, particularly in those ingesting diets containing adequate amounts of protein. Results from clinical trials using daily haemodialysis strongly suggest that thrice-weekly haemodialysis regimens are only marginally adequate for achieving weekly phosphorus balance in many patients with ESRD. The safety of large oral doses of calcium as a phosphate-binding agent in patients with ESRD has also been questioned because excess amounts of calcium that are absorbed from the gastrointestinal tract may lead to ongoing calcium retention in those with little or no residual renal function. Arterial calcification and cardiac valve calcification are two serious complications that adversely affect cardiovascular haemodynamics. The use of large, often supraphysiological, doses of calcitriol or other vitamin D sterols to treat secondary hyperparathyroidism may aggravate hypercalcaemia and hyperphosphataemia, further increasing the risk of soft tissue and vascular calcification. Phosphate-binding agents that do not contain calcium, new vitamin D analogues and calcimimetic compounds offer new therapeutic alternatives for managing renal osteodystrophy. The integration of these novel agents into existing treatment regimens may provide safer and more effective methods for controlling secondary hyperparathyroidism and renal bone disease, while limiting the risks of soft tissue and vascular calcification in patients with CRF.
Nephrol Dial Transplant 2003 Jun
PMID:Medical management of secondary hyperparathyroidism in chronic renal failure. 1277 Dec 90

More than 60% of patients on chronic haemodialysis (HD) have a serum phosphate level above 5.5 mg/dl (1.75 mmol/l), which recently has been recommended as an appropriate target in patients with end-stage renal disease (ESRD). Preventing hyperphosphataemia and elevated Ca x P product not only ameliorates the progression of secondary hyperparathyroidism and bone disease, but also appears to reduce cardio-vascular morbidity and mortality from vascular calcifications. Dietary phosphate restriction and the administration of aluminium and calcium salts have been the principal means of phosphate control over the last decade. Unfortunately, the protean disturbances of toxic aluminium accumulation in the body virtually eliminated aluminium from clinical practice. Calcium-based therapy, although well tolerated, results in frequent hypercalcaemia when administered concurrently with vitamin D analogues, despite a decrease in the concentration of dialysate calcium. Sevelamer (Renagel((R))) has been a novel, non-absorbable calcium- and aluminium-free synthetic polymer. In initial studies, sevelamer reduced serum phosphate, Ca x P product and parathyroid hormone (PTH) in a manner comparable with calcium acetate therapy. However, the effect on PTH levels may prove to be inconsistent. It seems somewhat less effective in binding phosphate than aluminium, although no direct comparisons have been made. In a recent study, it attenuated the progression of vascular calcification in HD patients. It also binds bile acids, resulting in substantially lower low-density lipo-protein cholesterol levels. The major obstacle to its current use is a substantial increase in the cost associated with sevelamer therapy.
Nephrol Dial Transplant 2003 Jul
PMID:Hyperphosphataemia and treatment with sevelamer in haemodialysis patients. 1281 70

Secondary hyperparathyroidism is a major complication in uremic patients undergoing dialysis. Various active metabolites of vitamin D are used as oral treatment; however, in some patients, parathyroid hormone (PTH) is not ideally suppressed. Intravenous injection of an active form of vitamin D inhibits PTH more effectively than does oral administration. However, intravenous administration is often restricted by the complication of hypercalcemia. In the calcitriol analog 22-oxacalcitriol (OCT), the 22nd carbon atom is replaced by oxygen. The OCT analog has been reported to have a lesser hypercalcemic effect than does calcitriol. The present study was planned to determine whether intraperitoneal administration of OCT would be a more effective treatment of secondary hyperparathyroidism than intravenous administration is in CAPD patients who manage themselves at home. The results showed that OCT is stable in dialysis solution and that its intraperitoneal administration was effective for suppressing PTH in patients with secondary hyperparathyroidism.
Adv Perit Dial 2003
PMID:The effect of intraperitoneal 22-oxacalcitriol on secondary hyperparathyroidism in continuous ambulatory peritoneal dialysis patients (IPOX study). 1476 68

Paricalcitol [Zemplar: Abbott Laboratories, Abbott Park, IL, U.S.A.] is efficient for treating secondary hyperparathyroidism in patients on maintenance hemodialysis (HD). Zemplar is thought to be more potent than calcitriol and has been reported to cause less hypercalcemia and hyperphosphatemia. Here, we report a 1-year follow-up on patients from one inner-city dialysis unit. We reviewed the charts of 100 patients and collected data for 1 year. Patients were stratified into four groups depending upon their intact parathormone (iPTH) levels. Hemoglobin (Hb) and erythropoietin (EPO) doses were determined. More than 50% of patients had iPTH levels greater than 300 pg/mL. Mean Ca and PO4 levels were not significantly different, but Zemplar doses were significantly different in all groups. None of the patients had symptomatic bone disease. Seven patients were changed to low-Ca dialysate (1.0 mEq/L) secondary to hypercalcemia (Ca > 11.5 mg/dL) and severe secondary hyperparathyroidism. Interestingly, patients with low iPTH (< 100 pg/microL) showed relative EPO resistance, and patients with high iPTH (> 600 pg/microL) required smaller EPO doses. An inverse relationship was observed between Zemplar and EPO dose. The effect of Zemplar on EPO responsiveness needs to be confirmed in a larger study. Our data suggest that severe secondary hyperparathyroidism is frequent despite aggressive paricalcitol therapy in our inner-city HD population. To control severe secondary hyperparathyroidism in these patients, dietary and medication compliance may need to be supplemented with more effective non-calcium phosphate binders or calcimimetic agents, or both.
Adv Perit Dial 2003
PMID:Severe hyperparathyroidism despite paricalcitol therapy: one-year follow-up. 1476 69

In the early stages of renal failure, hyperparathyroidism develops as a compensatory mechanism to control serum levels of calcium, phosphorus and calcitriol. As kidney disease progresses, this ability to maintain mineral homeostasis is lost, leading to the development of renal osteodystrophy (ROD). Over the past decade, the pattern of ROD seen in patients with chronic kidney disease (CKD) has changed. Previously, the majority of patients had mixed uraemic osteodystrophy or aluminium-related osteomalacia. The decreased use of aluminium-based phosphate binders, coupled with improvements in the management of hyperphosphataemia, led to a reduction in the prevalence of these types of ROD. Since the mid-1990s, there has been an increase in the prevalence of adynamic bone disease as a result of increased suppression of parathyroid hormone through the use of calcium-based phosphate binders and calcitriol therapy. Adynamic bone disease is also associated with several clinical factors, such as older age, use of continuous ambulatory peritoneal dialysis and the presence of diabetes mellitus, as well as the use of calcitriol therapy. Studies of calcium metabolism in patients with CKD have shown that adynamic bone disease is a distinct clinical condition that leads to hypercalcaemia via mechanisms different from that seen in high-turnover bone disease. As high calcium x phosphorus product has been associated with soft tissue and vascular calcifications, and increased mortality, optimizing bone health may be an important way of reducing cardiovascular risk in patients with CKD. To do this, novel, effective, non-calcium, non-aluminium phosphate binders will be necessary.
Nephrol Dial Transplant 2004 Mar
PMID:The importance of bone health in end-stage renal disease: out of the frying pan, into the fire? 1512 48

Aluminium- or calcium-based phosphate-binding agents traditionally have been used to treat hyperphosphataemia in patients with end-stage renal disease. Although these agents effectively lower serum phosphorus levels, they are associated with serious side effects. Aluminium-based agents are associated with bone toxicity, renal osteodystrophy and encephalopathy, and calcium-based agents increase the risk of hypercalcaemia and cardiovascular calcification. Consequently, there remains a need for new, safe and effective non-calcium-, non-aluminium-based alternative treatments. Fortunately, several new agents are now available or are in the late stages of development, including sevelamer hydrochloride and lanthanum carbonate. Although sevelamer hydrochloride represents a step forward in the management of hyperphosphataemia, it has several drawbacks and is far from being the ideal phosphate binder. Lanthanum carbonate is the most recent non-calcium, non-aluminium phosphate binder to be developed for the treatment of hyperphosphataemia. Animal studies have shown it to be as effective as aluminium, without the associated toxicity. In clinical studies, lanthanum carbonate significantly reduced serum phosphorus levels, compared with placebo. It shows a similar efficacy to calcium carbonate in controlling serum phosphorus levels, but requires lower doses. In addition, lanthanum carbonate is at least as well tolerated as calcium carbonate, but is not associated with hypercalcaemia. Importantly, it has a positive effect on bone histology, with no evolution towards low bone turnover. Lanthanum carbonate, therefore, moves closer to the ideal phosphate binder.
Nephrol Dial Transplant 2004 Mar
PMID:Improving phosphate-binder therapy as a way forward. 1512 50

Secondary hyperparathyroidism (SHPT) is associated with parathyroid gland hyperplasia, increased parathyroid hormone (PTH) production and secretion, disturbed bone and mineral metabolism, soft tissue calcification and an increased risk of death. The condition is an almost universal complication of end-stage renal disease (ESRD) and currently is managed by treatment with phosphate binders and vitamin D compounds, both of which are associated with significant side effects, including hypercalcaemia and hyperphosphataemia. Therapy with calcimimetics is a new approach to the treatment of SHPT. These agents act at the calcium-sensing receptor (CaR), where they increase the sensitivity of the receptor to ionized serum calcium. Activation of the CaR results in a rapid reduction in PTH secretion. The calcimimetic drug cinacalcet HCl currently is undergoing clinical trials in dialysis patients who have uncontrolled SHPT, despite treatment with vitamin D compounds and/or phosphate binders. Clinical trials have confirmed that the drug rapidly reduces plasma PTH, phosphorus and calcium-phosphorus product (Ca x P) levels, and that levels of PTH, phosphorus and Ca x P remain suppressed for up to 3 years. In clinical trials, cinacalcet HCl was a well-tolerated drug; only nausea and vomiting occurred more frequently in patients who took cinacalcet HCl than in those who took placebo, and the occurrence of transient hypocalcaemia was limited to the initial phase of the treatment. Cinacalcet HCl is therefore a potentially highly effective and well-tolerated treatment for SHPT in patients with ESRD.
Nephrol Dial Transplant 2004 Aug
PMID:Clinical experience with cinacalcet HCl. 1528 57

Vascular calcification is the most common type of extra-osseous calcification in end-stage renal disease (ESRD), manifesting as both medial and intimal calcification of large arteries. It is highly prevalent, often progressive and is associated with reduced arterial elasticity and increased mortality. Risk factors for calcification in ESRD include age, duration of dialysis, diabetes mellitus, most probably an elevated calcium-phosphorus product (Ca x P) level, the dose of calcium-containing phosphate binders and the induction of the systemic inflammatory response. Uraemic calcification was thought to be a largely physico-chemical process facilitated by elevated Ca x P (i.e. "metastatic" calcification). It is now well established, however, that vascular smooth muscle cells actively take up phosphate to form bioapatite. This process is associated with a phenotypic transformation of vascular smooth muscle cells during which they express osteoblast markers. In addition to phosphate, various other factors are likely to increase bioapatite formation, e.g. lipids and inflammatory cytokines. There have also been relatively new insights relating to the role of endogenous inhibitors of calcification [i.e. matrix Gla protein and fetuin-A (alpha(2)-Heremans-Schmid glycoprotein)], in particular the downregulation of fetuin-A in systemic inflammation. Decreased serum fetuin-A has been shown to be associated with a reduced capacity to inhibit calcium phosphate precipitation in vitro and is predictive of mortality in dialysis patients. These new insights into pathogenesis may lead to better prevention and treatment of calcification (e.g. with calcimimetics, anti-cytokines, etc.). However, the only preventive approach to have been established prospectively to date is the replacement of calcium-containing phosphate binders with sevelamer HCl, a non-calcaemic phosphate binder. Yet, it remains unclear whether sevelamer HCl reduces vascular calcification by preventing episodes of hypercalcaemia and/or by reducing low-density lipoprotein (LDL)-cholesterol levels.
Nephrol Dial Transplant 2004 Aug
PMID:Vascular calcification in patients with end-stage renal disease. 1577 77


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