Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperphosphatemia is thought to underlie medial vascular calcification in advanced renal failure, but calcification can occur in other conditions in the absence of hyperphosphatemia, indicating that additional factors are important. To identify these factors, a model of medial calcification in rat aorta in vitro was developed. Aortic rings from rats were incubated in serum-free medium for 9 d, and calcification was measured as incorporation of (45)Ca and confirmed by histology and x-ray diffraction. No calcification occurred in normal vessels despite elevated free Ca(2+) and PO(4)(3-) concentrations of 1.8 mM and 3.8 mM, respectively, but mechanical injury resulted in extensive calcification in the media. Co-incubation studies revealed that normal aortas produced a soluble inhibitor of calcification in injured vessels that was destroyed by alkaline phosphatase. Culture of normal aortas with alkaline phosphatase resulted in calcification of the elastic lamina identified as hydroxyapatite by x-ray diffraction. This effect of alkaline phosphatase was not due to dephosphorylation of osteopontin (OPN), and calcification was not increased in aortas from OPN-deficient mice. The inhibitor was identified as pyrophosphate on the basis of the calcification induced in aortas cultured with inorganic pyrophosphatase, the inhibition of calcification in injured aortas by pyrophosphate, and the production of inhibitory levels of pyrophosphate by normal aortas. No calcification occurred under any conditions at a normal PO(4)(3-) concentration. It is concluded that elevated concentrations of Ca(2+) and PO(4)(3-) are not sufficient for medial vascular calcification because of inhibition by pyrophosphate. Alkaline phosphatase can promote calcification by hydrolyzing pyrophosphate, but OPN is not an endogenous inhibitor of calcification in rat aorta.
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PMID:Phosphate-induced vascular calcification: role of pyrophosphate and osteopontin. 1515 50

Pharmacologic interventions designed to control hyperparathyroidism (HPT) in uremic patients have limitations and potentially serious adverse clinical consequences. Hence, one still has to resort to surgical parathyroidectomy (PTX) in a considerable number of dialysis patients. The aim of the present study was to illustrate our experience with 26 renal dialysis patients who underwent surgical PTX. The main indications for PTX included iPTH > 1000 pg/mL associated with severe osteitis fibrosa, debilitating pruritus, marked soft tissue calcification, or hypercalcemia with hyperphosphatemia, which sometimes complicated vitamin D therapy. All patients were resistant to more conservative measures, including control of serum phosphate, attention to oral intake and dialysate calcium levels, and oral/intravenous administration of active vitamin-D-pulse therapy. Ultrasound and technetium 99-sestamibi scan were used to image the thyroid and the parathyroid glands. Total PTX with autotransplantation was performed in 23 patients; subtotal PTX was performed in 3 patients. Histology of frozen sections taken intraoperatively showed nodular changes in 14 and diffuse hyperplasia in 12 cases. During the 2-year follow-up period significant reductions in parathyroid hormone, alkaline phospatase blood levels, skeletal changes, and soft tissue calcifications were observed. Pruritus improved in half the cases. Some improvement in hemoglobin and hematocrit was also noticed. The complication rate after PTX was low. Transient postoperative hypocalcemia requiring intensification of calcium and vitamin D therapy was seen in cases with high preoperative alkaline phosphatase levels. Recurrence was observed in two cases. Hypoparathyroidism was not recorded. We conclude that surgical reduction of parathyroid mass is a safe and effective treatment for symptomatic disease not suppressible by pharmacologic means.
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PMID:Effectiveness of surgical parathyroidectomy for secondary hyperparathyroidism in renal dialysis patients in Qatar. 1535 Apr 84

Secondary hyperparathyroidism (SHP) is a frequent complication of long-term dialysis patients, and surgical parathyroidectomy remains necessary in patients resistant to medical therapy. The present paper reports single center results in subtotal parathyroidectomy, presenting diagnostic procedure, indications for parathyroidectomy, and postoperative course of metabolic and endocrine disorders. Forty-seven patients (25 males and 22 females), aged 25-60 years, regularly hemodialyzed between 3-23 years, have undergone parathyroidectomy at our Clinical Center during the last 10 years. The patients had plasma iPTH levels 8-45 times higher than the top normal limit, high values of alkaline phosphatase, calcemia on the upper normal level, and hyperphosphatemia. Radiographic changes characteristic for SHP were seen in all patients before parathyroidectomy, and the most common were subperiosteal resorptions (100%), bone cysts and periosteal neostosis (66%), and extraskeletal calcifications (98%). Enlarged parathyroid glands were seen by ultrasound in 62% of patients. All patients manifested pruritus and bone pain, 89% of them had myopathy, while other symptoms and signs were present in lower proportions. After parathyroidectomy, pruritus and myopathy reduced significantly, while pain in bones and joints remained. One patient had brown tumor at the maxillary bone that regressed gradually after parathyroidectomy. Significant decreases of phosphate and calcium levels were recorded in all but two patients on the very first postoperative day. Regular peroral and parenteral supplementations of calcium and vitamin D metabolites were used, but calcemia was not normalized until the end of the third week of the postoperative period. Serum alkaline phosphatase showed an increase after the surgery, thereupon a sudden and then slower decrease up to 1 year from the surgery. Plasma iPTH levels, checked on the 21st postoperative day, were close to the lower normal limit in all but two (4.3%) patients with persistent SHP, who required reoperation. In conclusion, subtotal parathyroidectomy was proved as a successful and safe treatment for patients with SHP resistant to medical therapy, and treatment was followed by improvement of clinical symptoms and metabolic disorders.
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PMID:Ten years' experience in subtotal parathyroidectomy of hemodialysis patients. 1571 30

This double-blind, placebo-controlled study evaluated the safety and efficacy of intravenous (i.v.) calcitriol (Calcijex) for treatment of secondary hyperparathyroidism (secondary HPT) in pediatric end-stage renal disease (ESRD) patients on hemodialysis (HD). After a 2 to 6-week washout period of all vitamin D compounds, patients with two consecutive PTH values > 400 pg mL(-1), calcium levels < or = 10.5 mg dL(-1) and calcium x phosphorus product values < or = 70 mg2 dL(-2) were eligible for the treatment phase. Patients received a bolus injection of calcitriol or placebo three times a week, immediately after dialysis for up to 12 weeks. Initial doses (0.5-1.5 microg) were based on the severity of secondary HPT. The dose was increased every two weeks by 0.25 microg until there was at least a 30% decrease in PTH from baseline, or Ca > 11.0 mg dL(-1), or Ca x P > 75 mg2 dL(-2). Overall, 11/21 (52%) patients in the calcitriol group had two consecutive > or = 30% decreases from baseline in serum PTH compared with 5/26 (19%) patients in the placebo group (P=0.03). The mean total alkaline phosphatase decreased from 274 to 232 IU L(-1) in the calcitriol group and increased from 547 to 669 IU L(-1) in the placebo group (P=0.002). The mean bone-specific alkaline phosphatase decreased from 72.5 to 68 microg L(-1) in the calcitriol group and increased from 105.3 to 148.5 microg L(-1) in the placebo group (P=0.03). The incidence of two consecutive occurrences of elevated calcium x phosphorus (Ca x P > 75 mg2 dL(-2)) product was higher in the calcitriol group than in the placebo group (P=0.01). Two consecutive occurrences of phosphorus > 6.5 mg dL(-1) occurred in 71% of the calcitriol group and 46% of the placebo group (P=0.14). Calcium levels > 10.5 mg dL(-1) were more common in the calcitriol group than in the placebo group (P=0.01). There was a direct relationship between serum phosphorus concentration and the percentage change in PTH from baseline in both the calcitriol group (r=0.46; P<0.0001) and the placebo group (r=0.21; P=0.0005). This study demonstrates that i.v. calcitriol, at initial doses of 0.5-1.5 microg, effectively reduces PTH levels in pediatric HD patients and that patients should be closely monitored for hyperphosphatemia and elevated Ca x P product.
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PMID:Intravenous calcitriol for treatment of hyperparathyroidism in children on hemodialysis. 1578 41

A prospective study was carried out to assay the level of serum intact parathormone and its correlation with biochemical parameters in patients with chronic renal failure (CRF). The study included 64 children (44 with CRF, and 20 age and sex matched controls). Serum intact parathormone (iPTH), serum creatinine, urea, calcium, inorganic phosphate and alkaline phosphatase were estimated. Creatinine clearance (Ccr) was estimated by Schwartz formula. Patients with CRF were divided into four groups based on their Ccr (mild CRF with mean Ccr 59.17 +/- 1:18.53 mL/min/1.73 m2 (n = 6) moderate CRF with mean Ccr 34.98 +/- 7.75 mL/min/1.73 m2 (n = 7); severe CRF with mean Ccr 17.71 +/- 5.40 mL/min/1.73 m2 (n = 15); and end-stage renal disease with mean Ccr 6.46 +/- 1.71 mL/min/1.73 m2 (n = 16). Mean serum iPTH levels were 93.00 +/- 46.62 pg/mL in CRF and 16.52 +/- 9.35 pg/mL in controls. Groupwise mean serum (iPTH) levels were 48.50 +/- 4.76, 67.29 +/- 7.91, 82.42 +/- 9.67 and 130.66 +/- 58.74 pg/mL in mild, moderate, severe CRF and endstage renal failure respectively. Mean serum iPTH level of CRF (93.00 +/- 46.42 pg/mL) negatively correlated with mean Ccr (22.02 +/- 18.53 mL/min/l.73 m2) (P < 0.001) and mean serum calcium (7.30 +/- 1.02 mg/dL) (P < 0.001) and positively correlated with mean inorganic phosphate (5.76 +/- 1.1 mg/dL) (P < 0.05) and mean alkaline phosphatase (355.14 +/- 185.53 UL) (P < 0.001). We conclude that increased iPTH level occur even early in the course of CRF and progressive hypocalcemia and hyperphosphatemia are the initiating factors for the development of hyperparathyroidism.
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PMID:Correlation of serum parathormone level with biochemical parameters in chronic renal failure. 1581 73

The management of hyperphosphatemia is essential to treat secondary hyperparathyroidism and to prevent ectopic calcification. Sevelamer hydrochloride (sevelamer), a new phosphate binder that contains neither aluminum nor calcium, which could be theoretically beneficial for the management of hyperphosphatemia in dialysis patients with secondary hyperparathyroidism who are receiving intravenous vitamin D metabolites (maxacalcitol or calcitriol). To reduce calcium loads, a dialysate calcium concentration of 2.5 mEq/L is recommended by Kidney Disease Outcome Quality Initiative (K/DOQI) guidelines. In Japan, a dialysate calcium concentration of 3.0 mEq/L prevails. We investigated the influence of dialysate calcium on the therapeutic effect of sevelamer in 40 hemodialysis patients who are under treatment of intravenous vitamin D metabolites for secondary hyperparathyroidism (VD(+)) and compared the results with those of 41 patients who had not received vitamin D metabolites (VD(-)). Serum phosphorus and calcium-phosphorus products showed no significant change by sevelamer in either the VD(+) subgroup of patients receiving hemodialysis with dialysate calcium of 2.5 mEq/L (DCa2.5) or those receiving hemodialysis with dialysate calcium of 3.0 mEq/L (DCa3.0), while serum phosphorus and calcium-phosphorus products decreased in both the VD(-) subgroups. Serum calcium decreased in the DCa2.5 subgroup and did not change in the DCa3.0 subgroup in both the VD(+) and the VD(-) subjects. Parathyroid hormone and alkaline phosphatase increased in the DCa2.5 subgroup and did not change in the Ca 3.0 subgroup in the VD(+) subjects. Serum calcium decreased in both subgroups in the VD(-) subjects. Parathyroid hormone obtained after sevelamer administration in the VD(-) group was within the target range of the K/DOQI guidelines. In conclusion, the concomitant use of sevelamer as a phosphate binder and the dialysate of calcium concentration of 2.5 mEq/L have possibilities for worsening secondary hyperparathyroidism in patients receiving intravenous vitamin D.
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PMID:The influence of dialysate calcium on the therapeutic effects of sevelamer hydrochloride in hemodialysis patients with secondary hyperparathyroidism under treatment of intravenous vitamin d metabolites. 1582 1

Tumoral calcinosis is a rare disorder of mineral metabolism among adolescents and young adults characterized by deposition of calcific masses around large joints. It is less commonly reported in pediatric population and commonly mistaken for bone tumors. Typical lab parameters include hyperphosphatemia with normal levels of serum calcium, parathyroid hormone (PTH) and alkaline phosphatase. A ten-year-old boy with typical features of tumoral calcinosis is presented.
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PMID:Tumoral calcinosis with hyperphosphatemia. 1627 68

Although renal osteodystrophy and vitamin D analogs may be related to survival in maintenance hemodialysis (MHD) patients, most studies have examined associations between baseline values and survival without accounting for variations in clinical and laboratory measures over time. We examined associations between survival and quarterly laboratory values and administered paricalcitol in a 2-year (July 2001-June 2003) cohort of 58,058 MHD patients from all DaVita dialysis clinics in USA using both time-dependent Cox models with repeated measures and fixed-covariate Cox models with only baseline values. Whereas hypercalcemia and hyperphosphatemia were robust predictors of higher death risk in all models, the association between serum calcium and mortality was different in time-varying models. Changes in baseline calcium and phosphorus values beyond the Kidney Disease Outcome Quality Initiative recommended targets were associated with increased mortality. Associations between high serum parathyroid hormone and increased death risk were masked by case-mix characteristics of MHD patients. Time-varying serum alkaline phosphatase had an incremental association with mortality. Administration of any dose of paricalcitol was associated with improved survival in time-varying models. Controlling for nutritional markers may introduce overadjustment bias owing to their strong collinearity with osteodystrophy surrogates. Whereas both time-dependent and fixed-covariate Cox models result in similar associations between osteodystrophy indicators and survival, subtle but potentially clinically relevant differences between the two models exist, probably because fixed models do not account for variations of osteodystrophy indices and changes in medication dose over time.
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PMID:Survival predictability of time-varying indicators of bone disease in maintenance hemodialysis patients. 1755 57

black triangle An oral formulation of paricalcitol has been developed for the prevention and treatment of secondary hyperparathyroidism in patients with stage 3 or 4 chronic kidney disease.black triangle Paricalcitol is a synthetic vitamin D analog that binds to the vitamin D receptor inducing suppression of parathyroid hormone (PTH) secretion.black triangle Oral paricalcitol was significantly more effective than placebo in treating secondary hyperparathyroidism in patients with stage 3 or 4 chronic kidney disease. In a pooled analysis of three well designed, 24-week trials, two consecutive reductions from baseline in intact PTH levels of >/=30% were achieved by significantly more paricalcitol than placebo recipients (91% vs 13%).black triangle In addition, mean levels of the biochemical bone markers serum bone-specific alkaline phosphatase, serum osteocalcin, and urinary pyridinoline were reduced from baseline to a significantly greater extent with paricalcitol than with placebo, indicating a reduction in bone turnover.black triangle Oral paricalcitol was well tolerated; there was no significant difference between paricalcitol and placebo recipients in the incidence of hypercalcemia, hyperphosphatemia, or elevated calcium-phosphorus product.
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PMID:Oral paricalcitol. 1700 90

Calciphylaxis (calcific uremic arteriolopathy) is a poorly understood and highly morbid syndrome of both vascular calcification and skin necrosis. The main histopathological finding is calcium deposits within arteriolar and small vessel walls, showing endovascular fibrosis associated with fat necrosis. The therapeutic strategy is to normalize the high calcium-phosphate products (Ca x P). When calciphylaxis is complicated with advanced renal hyperparathyroidism (HPT), parathyroidectomy (PTX) should be performed promptly. However, for patients with low PTH level, calciphylaxis is unresponsive to PTX, and such an approach may worsen hyperphosphatemia and hypercalcemia. We report two patients with calciphylaxis confirmed by skin biopsy. PTX was performed in both patients based on high PTH levels. PTH and Ca x P level decreased in both patients post PTX. In Case 1, the skin ulcers gradually improved and almost disappeared after PTX. However, in Case 2, new ulcers appeared after PTX. In Case 1, alkaline phosphatase (ALP) after PTX was approximately twice its level before surgery and PTX resulted in normalization of uptake on bone scintigraphy. However, no rise in ALP was noted in Case 2, probably due to long-term use of aluminum, which prevented bone formation. These findings suggest that differences in the extent of bone formation explain the different response in post-PTX ulcer healing.
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PMID:Two cases of calciphylaxis treated by parathyroidectomy: importance of increased bone formation. 1759 77


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