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PubMedDate not supplied

A conservative management protocol for calcific tendinitis of the shoulder.

OBJECTIVE: This paper presents a management protocol for calcific tendinitis and describes its effective application in 2 cases of calcific tendinitis of the supraspinatus tendon in middle-aged women. CLINICAL FEATURES: Two patients presented to a chiropractic clinic with previously diagnosed calcific tendinitis of the supraspinatus tendon. Both patients complained of chronic pain and tenderness in the shoulder region and had a limited range of shoulder motion as a result of the pain. Radiographs demonstrated calcific deposits in the region of the supraspinatus tendon. INTERVENTION AND OUTCOMES: Both patients were admitted to a treatment protocol involving approximately 20 sessions of phonophoresis (driving of medication into tissue by ultrasound) with Movelat cream followed by cross-friction massage to the supraspinatus tendon and range of motion exercises. A second set of radiographs was requested. The calcific deposits, clearly seen on the previous radiographs, were no longer visible, and symptoms were resolved. At 4-month follow up, both patients continued to be symptom-free. CONCLUSION: The result of these studies indicates that the management of calcific tendinitis falls within the scope of chiropractic practice and supports the use of a trial period of conservative management in cases of calcific tendinitis before consideration of surgical treatment.

Calcinosis↗
PubMed2002

Hypothalamic digoxin related membrane Na+-K+ ATPase inhibition and familial basal ganglia calcification.

The isoprenoid pathway produces three key metabolites-digoxin (membrane sodium-potassium ATPase inhibitor and regulator of intracellular calcium-magnesium ratios), dolichol (regulator of N-glycosylation of proteins) and ubiquinone (free radical scavenger). The pathway was assessed in a rare and specific type of familial basal ganglia calcification described. The family had a coexistence of basal ganglia calcification (six out of 10 cases), schizophrenia, Parkinson's disease, Alzheimer's disease, rheumatoid arthritis, systemic tumours and syndrome X and were all right hemispheric dominant. The isoprenoid pathway was also studied for comparison in right hemispheric dominant, bihemispheric dominant and left hemispheric dominant individuals. The isoprenoid pathway was upregulated with increased digoxin synthesis in familial basal ganglia calcification. Membrane sodium-potassium ATPase inhibition can lead on to increase in intracellular calcium and calcification of the basal ganglia. There was increase in tryptophan catabolites and a reduction in tyrosine catabolites. There was also an increase in dolichol and glycoconjugate levels with reduced lysosomal stability in these patients. The ubiquinone levels were low and free radical levels increased. The cholesterol-phospholipid ratio was increased and glycoconjugate level of the RBC membrane reduced in these group of patients. No significance difference was noted in family members with and without basal ganglia calcification. This findings were correlated with the pathogenesis of syndrome X, immune mediated diseases, degenerations, tumours and psychiatric disorders noted in the familial basal ganglia calcification described. The biochemical patterns obtained in familial basal ganglia calcification correlated with those in right hemispheric dominance.

Adult↗
PubMed2001

Algorithmic 3D simulation of breast calcifications for digital mammography.

We present a framework for algorithmic three-dimensional simulation of breast calcifications. The simulated calcifications can be viewed from any angle at a higher spatial resolution than currently available for digital mammography, and they can be placed onto a simulated or real mammographic background to provide example cases for computers and radiologists. In order to simulate calcification clusters, we also show how to simulate duct networks and terminal ductal lobular units. We evaluated the model with a double-blind evaluation of 60 cases with four experienced radiologists by mixing 30 cases of simulated calcification clusters on a real or simulated mammographic background with 30 cases of real breast calcification clusters digitized at a spatial resolution of 15 microm from high-resolution radiographs of 5 mm slices of breast specimens. The results indicate that the majority of the 2D projections of the 3D simulated calcifications compare favorably with the radiographic images of real breast calcifications.

Algorithms↗
PubMed1996

Electron beam computed tomography in the evaluation of cardiac calcification in chronic dialysis patients.

The purpose of this study was to assess the value of electron beam computed tomography in the detection of cardiac calcifications in coronaries and valves of dialysis patients and to determine the rate at which calcification progresses. Forty-nine chronic hemodialysis patients aged 28 to 74 years were compared with 102 non-dialysis patients aged 32 to 73 years with documented or suspected coronary artery disease, all of whom underwent coronary angiography. We used high-resolution electron beam computed tomography scanning to make 30 axial slices with a distance of 3 mm between each slice. The number of calcifications, the surface area, and the average and highest density values were measured. We calculated a quantitative coronary artery calcium score and assessed calcification of mitral and aortic valves. In dialysis patients, the measurements were repeated after 12 months. The coronary artery calcium score was from 2.5-fold to fivefold higher in the dialysis patients than in the non-dialysis patients. Hypertensive dialysis patients had higher calcium scores than non-hypertensive dialysis patients (P < 0.05). A stepwise, multiple regression analysis confirmed the importance of age and hypertension. No correlation between calcium, phosphate, or parathyroid hormone values and the coronary calcium score was identified; however, the calcium score was inversely correlated with bone mass in the dialysis patients (r = 0.47, P < 0.05). The mitral valve was calcified in 59% of dialysis patients, while the aortic valve was calcified in 55%. The coronary artery calcium score was correlated with aortic valvular, but not mitral valvular calcification. A repeat examination of the dialysis patients at an interval of 1 year showed a disturbing tendency for progression. Our data under-score the frequency and severity of coronary and valvular calcifications in dialysis patients, and illustrate the rapid progression of this calcification. Finally, they draw attention to hypertension as an important risk factor in this process.

Adult↗
PubMed2000

Portal venous calcifications 20 years after portosystemic shunting: demonstration by spiral CT with CT angiography and 3D reconstructions.

BACKGROUND: Evaluation of the value of spiral computed tomography (SCT), and postprocessing procedures in patients with extensive portal venous calcifications 20 years after portosystemic shunting was performed. METHODS: In two patients spiral CT (SCT) examinations of the abdomen (slice thickness 3 mm, table feed 6 mm/s) were performed prior and after application of 150 ml of contrast material administered at a flow rate of 4 ml/s. Axial images were reconstructed at 2 mm increments for postprocessing procedures and 6 mm increments for axial source images. Postprocessing was performed with a maximum intensity projection (MIP) and shaded surface display (SSD) imaging program. RESULTS: In both cases preoperative plain film radiography of the chest and abdomen showed large curvilinear calcifications located at the upper quadrant of the abdomen. The calcifications were directed along the expected axis and position of the portal vein and the portosystemic venous anastomosis. Axial CT slices and CTA showed that the calcifications were located in the vessel wall and that the portal vein lumen as well as the portosystemic venous anastomosis were patent. CONCLUSION: Long-standing portal hypertension is capable of causing portal venous calcifications due to mechanical stress to the vessel wall even years after performing portosystemic shunting. Typically, the calcifications are directed along the expected axis and position of the portal vein. SCT of the portal venous system is a reliable method to differentiate between calcifications in a thrombus or in the vessel wall, which may have therapeutic significance.

Angiography↗
PubMed2004

Screening biomaterials with a new in vitro method for potential calcification: porcine aortic valves and bovine pericardium.

Calcification is still a major cause of failure of implantable biomaterials. A fast and reliable in vitro model could contribute to the study of its mechanisms and to testing different anticalcification techniques. In this work, we attempted to investigate the potential calcification of biomaterials using an in vitro model. We purposed to test the ability of this model to screening possible anticalcification efficacy of different biomaterials. Porcine heart valve (PAV) and bovine pericardial (BP) tissues, fixed with glutaraldehyde were immersed into biological mimicking solution, where the pH and the initial concentrations of calcium and phosphoric ions were kept stable by the addition of precipitated ions during calcification. Kinetics of calcification was continuously monitored. The evaluation of biomaterials was carried out by comparing the kinetic rates of formation of calcific deposits. After 24 h, the calcific deposits on PAVs were found to be developed at significant higher rates (ranged from 0.81 x 10(-4)-2.18 x 10(-4)mol/min m2) than on BP (0.19 x 10(-4)-0.52 x 10(-4)mol/min m2) (one-way ANOVA, p < 0.05) depending on the experimental conditions (supersaturation of the solution). Parallel tests for similar biomaterials implanted subcutaneously in animal (rat) model showed after 49 days that significant higher amounts of total minerals deposited on PAV (236.73+/-139.12, 9 animals mg minerals/g dry net tissue) (mean+/-standard deviation) compared with that formed on BP (104.36+/-79.21, #9 mg minerals/g dry net tissue) (ANOVA, p < 0.05). There is evidence that in vitro calcification was correlated well with that of animal model and clinical data.

Animals↗
PubMed2016

Matrix stiffness promotes cartilage endplate chondrocyte calcification in disc degeneration via miR-20a targeting ANKH expression.

The mechanical environment is crucial for intervertebral disc degeneration (IDD). However, the mechanisms underlying the regulation of cartilage endplate (CEP) calcification by altered matrix stiffness remain unclear. In this study, we found that matrix stiffness of CEP was positively correlated with the degree of IDD, and stiff matrix, which mimicked the severe degeneration of CEP, promoted inorganic phosphate-induced calcification in CEP chondrocytes. Co-expression analysis of the miRNA and mRNA profiles showed that increasing stiffness resulted in up-regulation of miR-20a and down-regulation of decreased ankylosis protein homolog (ANKH) during inorganic phosphate-induced calcification in CEP chondrocytes. Through a dual luciferase reporter assay, we confirmed that miR-20a directly targets 3'-untranslated regions of ANKH. The inhibition of miR-20a attenuated the calcium deposition and calcification-related gene expression, whereas the overexpression of miR-20a enhanced calcification in CEP chondrocytes on stiff matrix. The rescue of ANKH expression restored the decreased pyrophosphate efflux and inhibited calcification. In clinical samples, the levels of ANKH expression were inversely associated with the degeneration degree of CEP. Thus, our findings demonstrate that the miR-20a/ANKH axis mediates the stiff matrix- promoted CEP calcification, suggesting that miR-20a and ANKH are potential targets in restraining the progression of IDD.

3' Untranslated Regions↗
PubMed1998

Cutaneous necrosis from calcific uremic arteriolopathy.

Calcific uremic arteriolopathy (calciphylaxis) is an uncommon complication of chronic renal failure that is associated with high morbidity and mortality. We report 16 patients (13 female) who presented between 1985 and 1996. All patients developed painful livido reticularis that progressed to cutaneous necrosis and ulceration (11 cases on the proximal extremities and five cases on the distal extremities). Two patients with predominately distal leg disease survived; the cause of death in the other 14 patients was sepsis (six patients), withdrawal from dialysis (three), cardiac arrest (three), and gastrointestinal hemorrhage (two). Mesenteric ischemia from intestinal vascular calcification occurred in two cases. Clinical factors identified included the use of warfarin therapy in seven cases and significant weight loss (>10% body weight) in seven cases in the 6 months preceding the development of calcific uremic arteriolopathy. Skin pathology was studied in 12 cases, with all showing calcific panniculitis and small vessel calcification. Electron microscopic spectral analysis of the mineral content of the calcific lesions in the subcutaneous tissue showed only calcium and phosphorous. In two cases, substitution of low molecular weight heparin for warfarin therapy resulted in clinical improvement. Current theories of pathogenesis and treatment are reviewed. This study confirms the high morbidity and mortality of calcific uremic arteriolopathy producing ischemic tissue necrosis while drawing attention to significant weight loss and warfarin therapy as risk factors for the development of ischemic tissue necrosis. Hyperbaric oxygen therapy warrants further study.

Adult↗
PubMed2003

Prevalence and progression of peripheral arterial calcifications in patients with ESRD.

BACKGROUND: Peripheral arterial calcifications are seen frequently in patients with end-stage renal disease (ESRD). However, prevalence and progression, as well as contributing factors, never were investigated in an unselected incident cohort of dialysis patients. METHODS: We investigated 155 patients with ESRD at the beginning of dialysis therapy and followed them up prospectively during the first year of either hemodialysis (n = 106) or peritoneal dialysis treatment (n = 49). The prevalence and progression of arterial calcifications during the first year were graded by a single radiologist on standardized plain radiographs of the pelvis and calves. Findings were analyzed in relation to sex, age, diabetes mellitus, dialysis modality, total and high-density lipoprotein cholesterol levels, lipoprotein(a) (Lp[a]) level, apolipoprotein(a) kringle-IV repeat polymorphism, calcium level, phosphorus level, intact parathyroid hormone level, and homocysteine level. RESULTS: Patients with peripheral arterial calcifications at the start of renal replacement therapy (RRT) (n = 104) were significantly older (P < 0.001), had diabetes more often (P < 0.001), and had greater Lp(a) concentrations (P = 0.03) and a trend to greater total cholesterol concentrations. Patients with progression of calcifications during the first year of RRT had significantly greater homocysteine levels (P = 0.036). Logistic regression analysis showed that patients without calcifications either at the beginning or after 1 year of RRT were younger (P = 0.01) and had significantly lower homocysteine (P = 0.004) and Lp(a) levels (P = 0.03) and less frequently had diabetes mellitus (P = 0.04). CONCLUSION: Our observations suggest that the prevalence of peripheral arterial calcifications in patients with ESRD is related to age, diabetes mellitus, and Lp(a) and homocysteine levels. Progression of arterial calcifications might be related to high plasma homocysteine concentrations.

Calcinosis↗
PubMed2004

Heart valve calcifications, survival, and cardiovascular risk in hemodialysis patients.

BACKGROUND: Cardiovascular (CV) calcifications constitute a strong risk marker, and recent studies in continuous ambulatory peritoneal dialysis patients have associated valvular calcifications to inflammation, mortality, and CV events. The prognostic value of cardiac valve calcifications and their relationship with left ventricular hypertrophy and background cardiovascular risk in hemodialysis patients is still unknown. METHODS: The prognostic value of heart valve calcifications (detected by echocardiography) for all-cause and CV death was tested in a cohort of 202 hemodialysis (HD) patients. RESULTS: Forty-seven patients had 1 or more calcified valves. Background CV complications were more frequent (P = 0.001) and left ventricular hypertrophy was more severe (P < 0.001) in patients with calcified valves than in those without this alteration. During the follow-up period (44 +/- 23 months), 96 patients died, 66 patients (69%) of CV causes. Valve calcifications were significantly associated with all-cause (P = 0.02) and CV mortality (P < or = 0.001). However, in statistical models adjusting for traditional and nontraditional CV risk factors and background CV complications and left ventricular mass index (LVMI), the relationship between calcified valves and incident all-cause and CV mortality was not significant. CONCLUSION: In HD patients, cardiac valve calcifications predict all-cause and CV mortality in unadjusted analyses, but these associations are not evident in models adjusting for background CV complications, LVMI, and other risk factors. Cardiac valve calcifications do not provide an independent contribution in the prediction of death and CV mortality.

Adult↗
PubMed2006

Disordered mineral metabolism and vascular calcification in nondialyzed chronic kidney disease patients.

It is well established that abnormalities in mineral metabolism are apparent early in the course of chronic kidney disease (CKD) and result in clinically relevant consequences such as renal osteodystrophy. Furthermore, there is emerging evidence linking some of these abnormalities (hyperphosphatemia) to the high cardiovascular morbidity and mortality experienced by nondialyzed patients with CKD. Most studies have evaluated vascular calcification in patients with stage 5 CKD. Reports published over the last 2 years show that the process begins rather early in CKD and is particularly severe among elderly and type 2 diabetic patients. Furthermore, "calcium begets calcium", such that the calcification burden in early CKD is an important predictor of subsequent progression, including the rapid increase seen in stage 5 CKD. There is an increasing body of evidence that supports the thesis that elevated serum levels of phosphorus and calcium and deficiency of inhibitors of calcification (for example, fetuin-A) are important in the progression of vascular calcification in patients with end-stage renal disease. However, the concentrations of calcium and phosphorus shown to induce mineralization in cell culture studies are not observed in most patients until late in stage 4 or stage 5 CKD. Cross-sectional and longitudinal studies have also been unable to show a correlation between serum levels of markers of disordered mineral metabolism and severity of vascular calcification. Future studies should evaluate the pathogenetic role of phosphorus retention, which occurs early in the course of CKD, in the induction and/or progression of vascular calcification. Finally, there is a need to identify alternative pathogenetic mechanisms that may be important causes of the high calcification burden observed early in CKD.

Bone Density↗
PubMed1995

Association between diabetic-autonomic-C-fibre-neuropathy and medial wall calcification and the significance in the outcome of trophic foot lesions.

The role of peripheral autonomic nerve failure in the development of medial arterial calcification is discussed controversially in the literature. In addition, the influence of medial wall calcification in the development of trophic foot lesions is still not fully understood. We have compared 28 diabetic patients with cardiac autonomic failure and/or decreased acetylcholine-induced sweat response with 22 diabetic patients without evidence of diabetic neuropathy and 27 healthy control subjects. A strong association was found between medial wall calcification and diminished heart rate variation (p.001) or diminished peripheral sweat response (p < 0.001). Only one subject in the control group exhibited a calcification of the tunica media in the lower limb. Medial calcinosis was accompanied by a significant rise of systolic ankle blood pressure (p < 0.05). In addition, there was a strong relationship between medial wall calcification and trophic foot lesions (p < 0.0001). Our results demonstrate a strong association between sympathetic C-fibre neuropathy and the development of medial wall calcification, as well as between calcification of the tunica media and trophic foot ulceration. Further investigation is necessary to determine whether there is a causal connection between medial arterial sclerosis and diabetic foot ulceration, or whether both are independent consequences of diabetic neuropathy.

Acetylcholine↗
PubMed2005

A randomized trial of intensive lipid-lowering therapy in calcific aortic stenosis.

BACKGROUND: Calcific aortic stenosis has many characteristics in common with atherosclerosis, including hypercholesterolemia. We hypothesized that intensive lipid-lowering therapy would halt the progression of calcific aortic stenosis or induce its regression. METHODS: In this double-blind, placebo-controlled trial, patients with calcific aortic stenosis were randomly assigned to receive either 80 mg of atorvastatin daily or a matched placebo. Aortic-valve stenosis and calcification were assessed with the use of Doppler echocardiography and helical computed tomography, respectively. The primary end points were change in aortic-jet velocity and aortic-valve calcium score. RESULTS: Seventy-seven patients were assigned to atorvastatin and 78 to placebo, with a median follow-up of 25 months (range, 7 to 36). Serum low-density lipoprotein cholesterol concentrations remained at 130+/-30 mg per deciliter in the placebo group and fell to 63+/-23 mg per deciliter in the atorvastatin group (P<0.001). Increases in aortic-jet velocity were 0.199+/-0.210 m per second per year in the atorvastatin group and 0.203+/-0.208 m per second per year in the placebo group (P=0.95; adjusted mean difference, 0.002; 95 percent confidence interval, -0.066 to 0.070 m per second per year). Progression in valvular calcification was 22.3+/-21.0 percent per year in the atorvastatin group, and 21.7+/-19.8 percent per year in the placebo group (P=0.93; ratio of post-treatment aortic-valve calcium score, 0.998; 95 percent confidence interval, 0.947 to 1.050). CONCLUSIONS: Intensive lipid-lowering therapy does not halt the progression of calcific aortic stenosis or induce its regression. This study cannot exclude a small reduction in the rate of disease progression or a significant reduction in major clinical end points. Long-term, large-scale, randomized, controlled trials are needed to establish the role of statin therapy in patients with calcific aortic stenosis.

Anticholesteremic Agents↗
PubMed2003

Serum levels of the fetuin-mineral complex correlate with artery calcification in the rat.

The present studies were carried out to evaluate the possible association between the presence of the fetuin-mineral complex in serum and vitamin D-induced artery calcification. The first experiment shows that there is a fetuin-mineral complex in the blood of rats in which extensive calcification of the artery media has been induced by treatment with vitamin D for 96 h, and that there is no detectable fetuin-mineral complex in the blood of rats in which artery calcification has been inhibited by concurrent treatment with ibandronate or osteoprotegerin. The second experiment shows that the timing of vitamin D-induced artery calcification correlates with the timing of the maximal increase in serum fetuin-mineral complex levels. Whereas both results indicate that serum levels of the fetuin-mineral complex are indeed associated with vitamin D-induced artery calcification, the biochemical basis for this association is presently unclear. One possibility is that high levels of the fetuin-mineral complex cause defects in the ability of fetuin to prevent the growth of the mineral component, which then seeds artery calcification. Another possibility is that the fetuin-mineral complex is the downstream product of a pathway that begins with the true causative agent, and that the serum level of the fetuin-mineral complex is a marker for the activity of this agent in blood. An unexpected finding of the present studies is that vitamin D-induced artery calcification is also correlated with a 65 to 75% reduction in serum fetuin, a reduction that appears to be caused by the clearance of the fetuin-mineral complex from serum.

Animals↗
PubMed2003

Teriparatide (human parathyroid hormone (1-34)) inhibits osteogenic vascular calcification in diabetic low density lipoprotein receptor-deficient mice.

Cardiovascular calcification is a common consequence of diabetes. High fat diets induce diabetes and arterial calcification in male low density lipoprotein receptor (LDLR) -/- mice; calcification occurs via Msx2 signaling that promotes the osteogenic differentiation of arterial myofibroblasts. We studied regulation of arterial osteogenesis by human parathyroid hormone (PTH) (1-34) (also called teriparatide) in LDLR -/- mice fed diabetogenic diets for 4 weeks. LDLR -/- mice were treated with vehicle or 0.4 mg/kg of PTH(1-34) subcutaneously five times/week. Gene expression was determined from single aortas and hind limb RNA by fluorescence reverse transcription-PCR. Valve calcification was determined by histological staining of cardiac sections using image analysis to quantify valve leaflet mineralization. PTH(1-34) increased bone mineral content (by dual energy x-ray absorptiometry) in LDLR -/- mice, with induction of osseous osteopontin (OPN) expression and serum OPN levels (>150 nM); PTH(1-34) did not significantly change serum glucose, lipids, body weight, or fat mass. PTH(1-34) suppressed aortic OPN and Msx2 expression >50% and decreased cardiac valve calcification 80% (8.3 +/- 1.5% versus 1.4 +/- 0.5%; p < 0.001). Of the known circulating regulators of vascular calcification (OPN, osteoprotegerin, and leptin), PTH(1-34) regulated only serum OPN. We therefore studied actions of PTH(1-34) and OPN in vitro on cells induced to mineralize with Msx2. OPN (5-50 nM) reversed Msx2-induced mineralization. PTH(1-34) inhibited mineralization by 40% and down-regulated Msx2 in aortic myofibroblasts. PTH(1-34) inhibits vascular calcification and aortic osteogenic differentiation via direct actions and potentially via circulating OPN. PTH(1-34) exerts beneficial actions at early stages of macrovascular disease responses to diabetes and dyslipidemia.

Animals↗
PubMed2004

Gender-based differences in the prognostic value of coronary calcification.

PURPOSE: To investigate the use of electron beam tomography (EBT) screening to predict all-cause mortality in a large cohort of asymptomatic women and men. METHODS AND RESULTS: We obtained mortality information from the National Death Index in 10377 asymptomatic individuals (40% women) referred by primary care physicians for coronary calcification screening. The average follow-up period was 5 +/- 3.5 years. Univariable and multivariable Cox proportional hazard models were developed to predict all-cause mortality. Women had a lower prevalence of coronary calcification and smaller calcification scores than men (p < 0.0001). Death rates were higher among older, diabetic, hypertensive, and currently smoking individuals both in women and in men. In unadjusted (chi-square = 82, p < 0.0001) as well as risk-adjusted (chi-square = 7, p = 0.007) Cox survival models, women had a greater probability of death than men in each strata of calcification. Relative risk (RR) ratios were increased 3.0-fold, 5.5-fold, and 5.5-fold, respectively, for women compared with men with coronary calcification scores of 101-399, 400-1000, and >1000 (p < 0.0001). Using receiver operating characteristics (ROC) curve analyses to assess coronary calcification added incremental prognostic value to Framingham risk scores (p < 0.0001). CONCLUSIONS: In this cohort of asymptomatic women, coronary calcification screening provided incremental prognostic information after adjustment for traditional risk factors. EBT may be a useful tool for risk stratification in women, where the early diagnosis of coronary heart disease (CHD) remains a strong challenge.

Adult↗
PubMed2005

1,25-Dihydroxyvitamin D3 but not cinacalcet HCl (Sensipar/Mimpara) treatment mediates aortic calcification in a rat model of secondary hyperparathyroidism.

BACKGROUND: Calcitriol treatment of secondary hyperparathyroidism (HPT) in chronic kidney disease (CKD) patients can lead to increased serum calcium and phosphorus, which have been associated as risk factors for vascular calcification. Cinacalcet HCl (Sensipar/Mimpara) {(alphaR)-(-)-alpha-methyl-N-[3-[3-(trifluoromethylphenyl)propyl]-1-napthalenemethanamine hydrochloride} lowers serum parathyroid hormone (PTH), calcium, phosphorus and calcium-phosphorous (CaxP) product in stage 5 CKD dialysis patients; however, its effects on vascular calcification are unknown. METHODS: Cinacalcet HCl (10 or 1 mg/kg, p.o. gavage), 1,25-dihydroxyvitamin D(3) (0.1 microg, s.c, calcitriol) or the combination was administered daily for 26 days in a rat model of secondary HPT [5/6 nephrectomy]. After dosing, aortic calcification was determined using the von Kossa staining method. Serum PTH and blood chemistries were determined on days 0, 26 and 0, 14, 26, respectively, prior to and after dosing. RESULTS: Calcitriol-treated rats had moderate to marked aortic calcification, whereas no significant calcification was observed in vehicle- or cinacalcet HCl-only treated groups. Co-administration of cinacalcet HCl with calcitriol did not attenuate the calcitriol-mediated increase in CaxP product or calcitriol-mediated aortic calcification. Both calcitriol and cinacalcet HCl therapy significantly reduced serum PTH levels. Calcitriol significantly elevated serum calcium, serum phosphorous and CaxP product above pretreatment levels, or those seen with vehicle or cinacalcet HCl. Cinacalcet HCl (10 or 1 mg/kg) decreased serum ionized calcium and decreased calcitriol-induced hypercalcaemia. CONCLUSION: Cinacalcet HCl and calcitriol both effectively reduce PTH, albeit via different mechanisms, but unlike calcitriol, cinacalcet HCl did not produce hypercalcaemia, an increased CaxP product or vascular calcification.

Animals↗
PubMed2005

Associations of serum fetuin-A with malnutrition, inflammation, atherosclerosis and valvular calcification syndrome and outcome in peritoneal dialysis patients.

BACKGROUND: Fetuin-A (alpha2-Heremans Schmid glycoprotein) has recently been identified as a circulating inhibitor of calcification and is regulated as a negative acute phase protein. However, its relationships with cardiac valvular calcification and atherosclerosis and outcome have not been evaluated in peritoneal dialysis (PD) patients. METHOD: We performed a prospective follow-up study in 238 PD patients with echocardiography done at baseline to detect cardiac valvular calcification and biochemical analysis performed for serum fetuin-A, albumin and C-reactive protein (CRP). RESULTS: Baseline serum fetuin-A concentration was (mean+/-SD) 0.309+/-0.068 g/l (normal range 0.4-0.95). Across the three tertiles of increasing serum fetuin-A, a significant trend effect was observed for age (P = 0.023), diabetes (P = 0.008), background atherosclerotic vascular disease (P = 0.010), cardiac valvular calcification (P = 0.002), serum albumin (P<0.001), subjective global assessment (P = 0.005) and CRP (P<0.001). Adjusting for CRP and calcium x phosphorus product, every 0.01 g/l increase in serum fetuin-A remained independently associated with a 6% decrease in the risk of valvular calcification (95% confidence intervals, 0.90-0.99; P = 0.028). Furthermore, serum fetuin-A showed a significant decrease across the four groups of patients with increasing components of the malnutrition, inflammation, atherosclerosis/calcification (MIAC) syndrome (P<0.001) and was the lowest among patients with all components of the MIAC syndrome (0.263+/-0.055 g/l) and highest among those who do not have the MIAC syndrome at all (0.338+/-0.063 g/l). Lower serum fetuin-A was associated with greater all-cause mortality (P = 0.0011) and fatal and non-fatal cardiovascular events (P = 0.0017), but its significance was lost when atherosclerotic vascular disease, valvular calcification, inflammation and malnutrition were included in the model. CONCLUSIONS: Serum fetuin-A showed important associations with valvular calcification, atherosclerosis, malnutrition and inflammation, and was linked to mortality and cardiovascular events in PD patients via its close relationships with the MIAC syndrome.

Arteriosclerosis↗