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)

Adynamic or aplastic bone remains an important medical issue in children with chronic renal failure. To prevent the development of adynamic bone during treatment of secondary hyperparathyroidism, clinical recommendations have been made to maintain intact PTH levels at 2 to 4 times the normal values, avoid hypercalcemia, and keep serum phosphorus levels within age-appropriate limits in children with chronic renal failure. Less-calcemic vitamin D analogs and calcium-free and aluminum-free phosphate-binding agents should be used in children who can tolerate these agents. It is important to remember to reduce or discontinue any medication, whether it is vitamin D, a calcium salt, or any other agent that significantly lowers PTH, especially when intact PTH levels decline rapidly (to < 150 pg/mL) and serum calcium levels are higher than 10 mg/dL.
Perit Dial Int
PMID:Adynamic bone revisited: is there progress? 1653 79

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.
Ther Apher Dial 2006 Aug
PMID:Therapeutic strategies for secondary hyperparathyroidism in dialysis patients. 1691 Nov 89

Vascular calcification is an active, cell-mediated process that can involve either the intima or media of the blood vessels. The current methods used to clinically measure vascular calcification cannot distinguish between intimal (invariably atherosclerotic) and medial calcification. The high calcification scores seen in patients with end-stage renal disease likely represent a composite of high calcification burden in both sites. The severity of vascular calcification has been associated with a variety of findings including left ventricular hypertrophy and angiographic vascular stenosis as well as with all-cause and cardiovascular mortality. There is increasing evidence that disordered mineral metabolism participates in the process of vascular calcification and is one of the mechanisms whereby hyperphosphatemia, hypercalcemia, and hyperparathyroidism enhance cardiovascular and all-cause mortality of end-stage renal disease patients. There are no studies showing improved outcomes of ESRD patients with aggressive control of disordered mineral metabolism. However, the preponderance of evidence argues strongly in favor of aggressive management of these abnormalities from starting early in the course of chronic kidney disease in the hope of improving patient outcomes.
Semin Dial
PMID:Vascular calcification and disordered mineral metabolism in dialysis patients. 1737 88

This prospective study was conducted with the aim of examining the efficacy of lowering dialysate calcium (dCa) in order to: (i) stimulate bone turnover in hemodialysis patients with biochemical signs of adynamic bone disease (ABD) (hypercalcemia, normal alkaline phosphatase and intact parathyroid hormone (iPTH) <150 pg/mL); and (ii) diminish hypercalcemia in patients with secondary hyperparathyroidism (sHPT) (hypercalcemia, high alkaline phosphatase and iPTH > 400 pg/mL), thus permitting the use of calcium-containing phosphorus binders and vitamin D metabolites. Patients were divided into: an ABD-treated group (24 patients), a sHPT-treated group (18 patients), an ABD-control group (12 patients) and a sHPT-control group (11 patients). For the ABD- and sHPT-treated patients, hemodialysis was conducted with dCa 1.5 mmol/L for three months and then with dCa 1.25 mmol/L for an additional three months, while in the control groups hemodialysis was conducted with dCa 1.75 mmol/L during the entire study. Reduction of dCa in patients with ABD caused a slight but insignificant decrease of Ca, but a significant and permanent increase of bone-specific alkaline phosphatase and intact parathyroid hormone level serum levels. Reduction of dCa in patients with sHPT slightly but insignificantly decreased Ca and intact parathyroid hormone level values. Nevertheless, this enabled the calcium-based phosphate binder dose to be raised and vitamin D3 metabolites to be introduced. Logistic regression analysis indicated that milder bone disease (both ABD and sHPT) was associated with more the favorable effect of dCa reduction. Thus, low dCa stimulated parathyroid glands and increased bone turnover in ABD patients, and enabled better control of mineral metabolism in sHPT patients.
Ther Apher Dial 2007 Apr
PMID:Effects of lowering dialysate calcium concentration on mineral metabolism and parathyroid hormone secretion: a multicentric study. 1802 74

The purpose of this crossover comparison study is to elucidate the differences between the effects of a novel calcitriol analog, 22-oxacalcitriol, and calcitriol on parathyroid hormone (PTH) and bone mineral metabolism in hemodialysis patients with secondary hyperparathyroidism (SHPT). Twenty-three patients with moderate to severe SHPT were included in a random 2 x 2 crossover trial with two vitamin D analogs (12 weeks for each treatment). Two patients withdrew during the run-in period for personal reasons. Serum electrolyte, bone metabolic marker, intact PTH (iPTH) and whole PTH (wPTH) levels were measured periodically. The primary endpoint measure was a decrease in serum iPTH level, and the secondary outcome measures included changes in serum calcium (Ca), phosphate (P), and metabolic bone marker levels. Both treatments decreased iPTH and wPTH levels by similar degrees. Serum Ca, P, and Ca x P product levels at the end of each treatment were comparable and the frequencies of hypercalcemia and hyperphosphatemia were also similar during each treatment period. 22-Oxacalcitriol significantly decreased the levels of bone metabolic markers, namely, bone-specific alkaline phosphate, intact osteocalcin, pyridinoline, and cross-linked N-telopeptide of type I collagen, after a 12-week treatment. In contrast, calcitriol did not change any of the levels of bone metabolic markers. The present study showed that 22-oxacalcitriol is equally effective for PTH suppression, and Ca and P metabolism. In addition, 22-oxacalcitriol might have putative actions on bone remodeling independent of its PTH suppression. Further study is necessary to confirm the effects of 22-oxacalcitriol on bone metabolism in SHPT.
Ther Apher Dial 2007 Jun
PMID:Effects of 22-oxacalcitriol and calcitriol on PTH secretion and bone mineral metabolism in a crossover trial in hemodialysis patients with secondary hyperparathyroidism. 1749 2

In June 2003, sevelamer hydrochloride became widely available in Japan and was expected to control hyperphosphatemia in hemodialysis patients without inducing hypercalcemia. To evaluate the impact of sevelamer therapy on mineral metabolism, we recruited 954 hemodialysis patients from 21 renal units just before the general release of sevelamer in Japan. The serum calcium, phosphate, and parathyroid hormone levels determined on enrollment were compared with those later measured in June 2004. Sevelamer was prescribed for 169 of the 859 patients for whom data were available in 2004. The mean calcium level, phosphate level, and calcium x phosphate product were all significantly reduced during the 12-month study period, but the intact parathyroid hormone (iPTH) level did not change. As a result, the percentage of patients who achieved a calcium x phosphate product of <55 mg(2)/dL(2) was significantly increased, but there were no changes in that of patients who achieved the target ranges for phosphate (3.5-5.5 mg/dL) or iPTH (150-300 pg/mL). Among sevelamer-treated patients, iPTH significantly increased, and this change was more marked in the patients with an initial iPTH level <150 pg/mL. Sevelamer was useful for reducing the serum calcium level and calcium x phosphate product, but hyperphosphatemia and hyperparathyroidism were not improved in our study population at 12 months after the release of sevelamer. A decrease in the calcium load might result in the exacerbation of hyperparathyroidism. However, among patients with relative hypoparathyroidism, sevelamer therapy may be beneficial for the prevention of adynamic bone disease.
Ther Apher Dial 2007 Jun
PMID:Influence of sevelamer on mineral metabolism and hyperparathyroidism in Japanese hemodialysis patients. 1749 3

Controlling serum phosphorus levels in patients with renal failure is critical. The use of oral phosphate-binding agents is universal for patients with end-stage kidney disease to reduce phosphate absorption. The therapeutic goal is to reduce serum phosphorus levels without disturbing calcium homeostasis or promoting accumulation of potentially toxic elements from the medication. Aluminum hydroxide effectively reduces serum phosphorus, but has largely been abandoned as a first-line phosphate binder because of hazards associated with metal absorption and tissue accumulation. Traditional calcium-based phosphate binders tend to promote hypercalcemia and calcium overloading, and are linked to accelerated cardiovascular calcification. Interest in aluminum-free, calcium-free phosphate-binding agents continues to grow. Sevelamer hydrochloride, a metal-free, calcium-free hydrogel, is not absorbed, has been proven safe and efficacious in controlling serum phosphorus, and is associated with attenuated progression of cardiovascular calcification. Lanthanum carbonate is a newer aluminum-free, calcium-free phosphate-binding agent. Lanthanum is a rare-earth trace metal with industrial and agricultural applications. As a therapeutic, this metal-based binder appears effective in reducing serum phosphorus, yet concerns remain about lanthanum accumulation in tissues during long-term oral administration. Similar to the metal aluminum, lanthanum is absorbed in the intestine and accumulates in body tissues, especially in the liver, bone, muscle, kidney, and brain. Moreover, the rate of intestinal absorption of lanthanum is enhanced in chronic renal failure. Our experience with aluminum hydroxide suggests caution regarding the long-term use of another metal-based agent that displays enhanced absorption in the uremic state and progressive tissue accumulation.
Semin Dial
PMID:Lanthanum carbonate as a first-line phosphate binder: the "cons". 1763 23

We have previously suggested that when parathyroid glands progress to nodular hyperplasia, secondary hyperparathyroidism (2HPT) may be refractory to medical treatments, including treatment with Maxacalcitol (OCT). In the present study we evaluated the clinical features and hyperplastic patterns of parathyroid glands in patients who underwent parathyroidectomy (PTx) after being withdrawn from OCT. One hundred and eighty-seven advanced 2HPT patients who had been withdrawn from OCT and required PTx were enrolled. At the start of OCT treatment, the patients had a mean age of 55.3 years and had been receiving hemodialysis (HD) for a mean period of 149 months. At the start of OCT treatment and at PTx, the mean intact PTH (i-PTH) levels were 772.8 +/- 446.0 and 855.5 +/- 420.5 pg/mL, respectively. The main reasons for withdrawal of OCT treatment were persistently high PTH (n = 148), hypercalcemia (n = 79), hyperphosphatemia (n = 65), and progressive symptoms (n = 60). We classified the parathyroid glands by hyperplastic pattern into four categories: diffuse hyperplastic gland (D), early nodularity in diffuse hyperplastic gland (EN), nodular hyperplastic gland (N), and single nodular gland (SN). The mean total excised gland weight was 2592.6 mg. Out of a total of 706 glands, 118 were classified as D, 66 as EN, 436 as N, and 86 as SN. All patients had at least one nodular hyperplastic gland or single nodular gland. The mean number of nodular hyperplastic glands and/or single nodular glands was 2.9. All hemodialysis patients with advanced OCT-refractory 2HPT who underwent PTx had at least one nodular hyperplastic gland or single nodular gland.
Ther Apher Dial 2007 Aug
PMID:Clinical features and hyperplastic patterns of parathyroid glands in hemodialysis patients with advanced secondary hyperparathyroidism refractory to maxacalcitol treatment and required parathyroidectomy. 1766 32

Reports of tumoral calcinosis (TC) in peritoneal dialysis (PD) patients are rare. Reported PD patients with TC also had hyperparathyroidism. A 67-year-old man on continuous ambulatory PD for almost 3 years developed TC of the right wrist and knee and both shoulders and feet. In the 2 years preceding the diagnosis of TC, this patient's serum parathyroid hormone levels were consistently low (17 +/- 12 pg/ mL). Hypercalcemia had been found in 32% of the serum samples, hyperphosphatemia in 91%, and elevated Ca x P product in 78% of the samples. At presentation with TC, serum C-reactive protein was elevated, and serum levels of vitamin D compounds were below normal. Four months after the diagnosis of TC, the patient died with a combination of gastrointestinal and retroperitoneal bleeding episodes and septic events. Tumoral calcinosis may develop in PD patients without hyperparathyroidism. Sustained hyperphosphatemia and high Ca x P product are important in the pathogenesis of uremic TC. Elevated indices of inflammation may accompany TC. Studies are needed to identify other important factors in the pathogenesis of TC in PD patients and to evaluate treatment methods.
Adv Perit Dial 2008
PMID:Tumoral calcinosis without hyperparathyroidism in a patient on continuous ambulatory peritoneal dialysis. 1898 17

The management of hemodialysis patients with chronic kidney disease-mineral bone disorder includes treatment to control levels of calcium, phosphorus and parathyroid hormone, so as to prevent bone and soft-tissue complications. Recently, pleiotropic effects of active vitamin D have attracted much attention, and its effect on outcome has also gained recognition. However, administration of active vitamin D may cause hypercalcemia and hyperphosphatemia. Now, the use of a novel class of drugs, cinacalcet hydrochloride, has been proposed as a strategy to reduce parathyroid hormone secretion, while decreasing levels of serum calcium, phosphorus, and calcium x phosphorus products. Among subjects with secondary hyperparathyroidism undergoing hemodialysis, combined therapy with cinacalcet and vitamin D sterols improved achievement of the biochemical targets for chronic kidney disease-mineral bone disorder recommended by the guidelines.
Ther Apher Dial 2008 Oct
PMID:Role of cinacalcet in management of mineral bone disorder in chronic kidney disease (control of calcium, phosphorus and parathyroid hormone). 1903 24


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