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PubMed2005

Relationship of eye burns with calcifications of the cornea?

INTRODUCTION: The clinical pattern of corneal calcification has been considered to be a part of chronic eye diseases, such as uveitis, severe glaucoma, keratitis and eye burns. Since, in some cases of eye burns, we have found corneal calcifications to be related to the initial calciferous caustic agents and to the use of phosphate-buffer-containing fluids, we have reviewed our files of clinical eye burns for the incidence and appearance of corneal calcification. METHODS: A total of 176 burnt eyes of 98 patients suffering from severe eye burns were retrospectively reviewed. The following data set was acquired: the type of caustic agent, the time of the burns, the delay and type of immediate treatment and the time and type of first aid, the subsequent medication, the clinical grading and the later results. RESULTS: Calciferous burning agents and corneal calcification are correlated (P<0.01). Initial single rinsing with phosphate does not produce corneal calcification (P=0.134). There is evidence that corneal calcifications are correlated with chronically administered phosphate-buffered eye drops (P<0.005). DISCUSSION: Eye burns followed by calcifications follow two different major patterns: the corrosive substance contained calcium or the continued therapy was applied with phosphate-buffered eye drops. We present case reports of three different types of eye burns and later therapy resulting in corneal calcification. Corneal calcifications are presumably related to longer-lasting phosphate application. One suspicious mechanism is the low content of calcium ion stabilizing proteins such as hyaluronate or fetuin in treatments for severe eye burns. The exceeding of the solubility product of Ca(2+) and PO(4) (-) results in the precipitation of calcium phosphates. In cases of chronic corneal disturbance, we recommend the elimination of phosphate-buffered medications to prevent corneal calcification.

Adolescent↗
PubMed1988

Evolution and regression of pancreatic calcification in chronic pancreatitis. A prospective long-term study of 107 patients.

Pancreatic calcifications are virtually pathognomonic of chronic pancreatitis and develop in up to 90% of patients with alcoholic chronic pancreatitis in series with long-term results. We investigated the natural course of pancreatic calcification in a prospective longitudinal study over the past 23 yr. All patients were studied at regular intervals with particular regard to etiology, clinical findings, surgery, pancreatic function, and pancreatic calcification visible by x-ray (e.g., film series in three projections centered on the pancreas). We evaluated the findings of 107 patients with x-ray documentation of pancreatic calcification in at least three film series over a period of 4 yr or longer. Eighty-four patients had alcoholic chronic pancreatitis (group A) and 23 patients had nonalcoholic chronic pancreatitis (group B). Four hundred seventy-two film series of group A and one hundred forty-two film series of group B were reviewed independently by two expert teams. Both series were graded according to a score system in terms of intensity and distribution of pancreatic calcification (correlation of grading r = 0.91). The duration of calcification averaged 10 yr in group A and 12.6 yr in group B. Similar dynamic changes of pancreatic calcification were noted in groups A and B. Chronologically, three phases of evolution could be distinguished. After an initial increase (phase 1), greater than 50% of cases reached a plateau of stationary calcification (phase 2). Approximately one-third of cases showed a marked decrease of calcification in late phases of chronic pancreatitis (phase 3). Dissolution of pancreatic stones was related primarily to duration of chronic pancreatitis (duration of calcification and marked pancreatic dysfunction), and occurred frequently (but not exclusively) in patients after ductal drainage procedures. These results indicate that spontaneous dissolution of pancreatic stones is a rather common biologic phenomenon. The factors responsible for dissolution of stones remain to be elucidated.

Adolescent↗
PubMed1996

Coronary risk factors measured in childhood and young adult life are associated with coronary artery calcification in young adults: the Muscatine Study.

OBJECTIVES: This study was designed to estimate the prevalence of coronary artery calcification in young adult men and women and to examine the association between the presence of coronary artery calcification and coronary risk factors measured in childhood and young adult life. BACKGROUND: Electron beam computed tomography is a sensitive, noninvasive method for detecting coronary artery calcification, a marker of the atherosclerotic process. Coronary artery calcification is associated with coronary risk factors in older adults. METHODS: Subjects (197 men, 187 women) had coronary risk factors measured in childhood (mean age 15 years) and twice during young adult life (mean ages 27 and 33 years). Each underwent an electron beam computed tomographic study at their second young adult examination. RESULTS: The prevalence of coronary artery calcification was 31% in men and 10% in women. Increased body size, increased blood pressure and decreased high density lipoprotein (HDL) cholesterol levels were the coronary risk factors that showed the strongest association with coronary artery calcification. Significant odds ratios for coronary artery calcification, using standardized risk factor measurements at a mean age of 33 years in men and women, respectively, were 6.4 and 13.6 for the highest decile of body mass index, 6.4 and 6.4 for the highest decile of systolic blood pressure and 4.3 and 4.7 for the lowest decile of HDL cholesterol. CONCLUSIONS: Coronary artery calcification is more prevalent in men in this young adult population. Coronary risk factors measured in children and young adults are associated with the early development of coronary artery calcification. Increased body mass index measured during childhood and young adult life and increased blood pressure and decreased HDL cholesterol levels measured during young adult life are associated with the presence of coronary artery calcification in young adults.

Adolescent↗
PubMed1996

The dilemma of diagnosing coronary calcification: angiography versus intravascular ultrasound.

OBJECTIVES: We sought to determine whether careful examination of angiograms in conjunction with other clinical information could reliably detect, quantitate and localize target lesion calcification before a coronary intervention. BACKGROUND: The presence, extent and location of calcium in coronary artery lesions are important determinants of outcome after coronary intervention. Intravascular ultrasound is proposed as a superior technique for identifying patients with coronary artery calcification. However, the precise role of this costly and invasive method has not yet been established. METHODS: Target lesion calcification was assessed in 183 patients (155 men; mean [+/-SD] age 58 +/- 10 years) by angiography and intravascular ultrasound before a planned percutaneous coronary intervention. RESULTS: Ultrasound detected calcium in 138 patients (>90 degrees in 56, 91 degrees to 180 degrees in 52, 181 degrees to 270 degrees in 22 and > 270 degrees in 8), whereas angiography showed calcification in 63 (1+ in 32, 2+ in 27 and 3+ in 4). The two techniques agreed in 92 patients and disagreed in 91. Sensitivity and specificity of angiography were 40% and 82%, respectively. The arc of calcium by ultrasound was greater in patients with angiographically visible calcification (175 degrees +/- 85 degrees vs. 108 degrees +/- 71 degrees, p=0.0001). The depth of calcification by ultrasound was superficial in 61 patients (44%), deep in 68 (49%) and mixed in 8 (7%). The sensitivity of angiography in identifying superficial calcium was 35%. Of 120 patients without angiographically visible calcium at the target lesion site, 83 showed calcium by ultrasound. The only predictor of ultrasound calcium in these 120 patients was angiographic calcification elsewhere in the coronary tree (p=0.0001). The probability of any calcium and superficial >90 degrees calcium were 60% and 12%, respectively, in the 90 patients without angiographic calcifications anywhere in the coronary tree. CONCLUSIONS: Despite poor sensitivity, angiography may help identify patients requiring intravascular ultrasound. When it is angiographically visible, the arc of calcium is likely to be large and superficial. Angiographic calcification at a remote site is a predictor of angiographically undetected target lesion calcium. Patients without angiographic calcification in the coronary tree may not need routine ultrasound examination, as the likelihood of >90 degrees superficial calcium is low.

Aged↗
PubMed2004

Receptor activator of nuclear factor kappaB ligand and osteoprotegerin regulate aortic valve calcification.

OBJECTIVE: - Recent studies have suggested that valvular calcification in calcific aortic stenosis (AS) may be actively regulated. "Receptor Activator of Nuclear factor kappaB Ligand" (RANKL) and osteoprotegerin (OPG) are members of a cytokine system involved in bone turnover and vascular calcification. Their role in calcific AS is not known. METHODS AND RESULTS: - By immunohistochemistry using human aortic valves, RANKL was not expressed at relevant levels in controls but detectable in AS. OPG expression was marked in controls but significantly lower in AS. Areas containing focal calcification exhibited significantly less OPG-positive cells as compared to non-calcified regions. Stimulation with RANKL lead to a significant rise in matrix calcification, nodule formation, alkaline phosphatase activity, expression of the bone-type isoenzyme of alkaline phosphatase, and expression of osteocalcin in cultured human aortic valve myofibroblasts. Moreover, RANKL increased DNA binding of the essential osteoblast transcription factor cbfa-1. CONCLUSION: - RANKL and OPG are differentially expressed in calcific AS. In cultured human aortic valve myofibroblasts, RANKL promotes matrix calcification and induces the expression of osteoblast-associated genes, indicating a transition towards an osteogenic phenotype. These results suggest that the RANKL-OPG pathway may regulate valvular calcification in calcific AS?

Aortic Valve↗
PubMed1999

Elastin calcification and its prevention with aluminum chloride pretreatment.

Elastin, an abundant structural protein present in the arterial wall, is prone to calcification in a number of disease processes including porcine bioprosthetic heart valve calcification and atherosclerosis. The mechanisms of elastin calcification are not completely elucidated. In the present work, we demonstrated calcification of purified elastin in rat subdermal implants (Ca(2+) = 89.73 +/- 9.84 microgram/mg after 21 days versus control, unimplanted Ca(2+) = 0.16 +/- 0.04 microgram/mg). X-ray diffraction analysis along with resolution enhanced FTIR spectroscopy demonstrated the mineral phase to be a poorly crystalline hydroxyapatite. We investigated the time course of calcification, the effect of glutaraldehyde crosslinking on calcification, and mechanisms of inhibition of elastin calcification by pretreatment with aluminum chloride (AlCl(3)). Glutaraldehyde pretreatment did not affect calcification (Ca(2+) = 89.06 +/- 17.93 microgram/mg for glutaraldehyde crosslinked elastin versus Ca(2+) = 89.73 +/- 9.84 microgram/mg for uncrosslinked elastin). This may be explained by radioactive ((3)H) glutaraldehyde studies showing very low reactivity between glutaraldehyde and elastin. Our results further demonstrated that AlCl(3) pretreatment of elastin led to complete inhibition of elastin calcification using 21-day rat subdermal implants, irrespective of glutaraldehyde crosslinking (Ca(2+) = 0.73-2.15 microgram/mg for AlCl(3) pretreated elastin versus 89.73 +/- 9.84 for untreated elastin). The AlCl(3) pretreatment caused irreversible binding of aluminum ions to elastin, as assessed by atomic emission spectroscopy. Moreover, aluminum ion binding altered the spatial configuration of elastin as shown by circular dichroism (CD), Fourier transform infrared (FTIR), and (13)C nuclear magnetic resonance (NMR) spectroscopy studies, suggesting a net structural change including a reduction in the extent of beta sheet structures and an increase in coil-turn conformations. Thus, it is concluded that purified elastin calcifies in rat subdermal implants, and that the AlCl(3)-pretreated elastin completely resists calcification due to irreversible aluminum ion binding and subsequent structural alterations caused by AlCl(3).

Aluminum Chloride↗
PubMed1996

Extensive calcification of the mitral valve anulus: pathology and surgical management.

Extensive calcification of the mitral valve anulus is a pathologic entity frequently associated with degenerative valvular disease. The calcification process remains localized to the anulus in 77% of the cases. It may extend, however, to the underlying myocardium. Whenever an operation is necessary for an associated valve insufficiency, the question arises whether it is preferable to repair or to replace the valve and how to manage the calcification. In the first part of this paper the pathology of this disease is studied, and in the discussion a mechanism is proposed to explain the development of the process of calcification. In the second part, a new operation is described, which comprises the temporary detachment of the leaflets, en bloc resection of the calcium deposit, annular reconstruction, and valve repair. For patients in whom the calcification extends to the myocardium a "sliding atrioplasty" of the left atrium is described, which allows the area of exposed muscular fibers to be covered. Between 1986 and 1994, among 68 patients with extensive calcification of the anulus and severe mitral valve insufficiency, 67 benefited from these repair techniques. Ages ranged from 18 to 82 years (mean 62 years). Thirty-two patients had a billowing mitral valve (Barlow), 27 a fibroelastic deficiency, and two Marfan's disease. The calcification involved more than one third of the anulus in 88% of the patients, the posterior anulus in 10.5%, and the whole anulus in 1.5%. The calcification process extended to the myocardial wall in 12% of the patients and to the papillary muscles in 4.5%. In the group of 67 valve repairs, there were two hospital deaths (2.9%), no instances of anulus dehiscence, and no early reoperations. The follow-up period extended from 4 months to 8 years (mean 3 years 8 months). There were two late deaths, 2 and 17 months after the operations, for an actuarial survival of 93% at 7 years. Late reoperation (6 to 62 months) was necessary in four patients (6.4%) for residual mitral valve incompetence (n=2), hemolysis (n=1), or endocarditis (n=1). In one of these patients a new repair was possible, whereas the three other patients required a valve replacement. All patients but one survived the reoperation. Actuarial freedom from reoperation was 87% at 7 years. All 60 patients with valve repair were reviewed for this study by clinical examination and echocardiography. All but one were in functional class I or II. There was no incompetence or trivial residual mitral valve incompetence in 55 patients and moderate incompetence in five. Two thromboembolic events have been recorded for a linearized rate of 1%/pt-yr. This study shows that complete anulus decalcification and valve repair can be done safely in patients with mitral valve insufficiency and extensive calcification of the anulus, even when the calcification process deeply involves the myocardium. It also demonstrates that an initially good result remained stable up to 7 years.

Adolescent↗
PubMed1998

Testicular calcifications: incidence, histology and proposed pathological criteria for testicular microlithiasis.

PURPOSE: Testicular microlithiasis is a clinical syndrome in which men present with innumerable testicular calcifications. Indirect evidence suggests that this syndrome may be associated with an increased risk of germ cell neoplasia. The incidence and types of testicular calcification in normal and diseased testes is unknown. MATERIALS AND METHODS: A series of 131 orchiectomy specimens were reviewed, including 79 germ cell tumors, and 100 entirely embedded autopsy testes in men with no known testicular pathology. RESULTS: Two types of calcifications were identified. Hematoxylin bodies, consisting of amorphous calcific debris, were present in 6 cases associated with germ cell tumors. In contrast, laminated calcifications were found not only in association with germ cell tumors (35 cases), but also in 2 of 4 cryptorchid testes and 6 of the remaining 145 testes (4%). Of these calcifications 61% were multiple. When laminated calcifications were associated with germ cell tumors there was an increased incidence of extension beyond the tunica albuginea (43 versus 21%) and lymphatic invasion (52 versus 17%, p = 0.046 and 0.012, respectively). CONCLUSIONS: Testicular calcifications are heterogeneous. Hematoxylin bodies are specific for germ cell tumors but laminated calcifications, while more common in germ cell tumors, also occur in otherwise normal testes. The pathological criteria for testicular microlithiasis should include the identification of multiple laminated calcifications within seminiferous tubules.

Adolescent↗
PubMed2000

The effect of type 1 diabetes mellitus on the gender difference in coronary artery calcification.

OBJECTIVES: To examine whether the gender difference in coronary artery calcification, a measure of atherosclerotic plaque burden, is lost in type 1 diabetic patients, and whether abnormalities in established coronary heart disease risk factors explain this. BACKGROUND: Type 1 diabetes abolishes the gender difference in coronary heart disease mortality because it is associated with a greater elevation of coronary disease risk in women than men. The pathophysiological basis of this is not understood. METHODS: Coronary artery calcification and coronary risk factors were compared in 199 type 1 diabetic patients and 201 nondiabetic participants of similar age (30 to 55 years) and gender (50% female) distribution. Only one subject had a history of coronary disease. Calcification was measured with electron beam computed tomography. RESULTS: In nondiabetic participants there was a large gender difference in calcification prevalence (men 54%, women 21%, odds ratio 4.5, p < 0.001), half of which was explained by established risk factors (odds ratio after adjustment = 2.2). Diabetes was associated with a greatly increased prevalence of calcification in women (47%), but not men (52%), so that the gender difference in calcification was lost (p = 0.002 for the greater effect of diabetes on calcification in women than men). On adjustment for risk factors, diabetes remained associated with a threefold higher odds ratio of calcification in women than men (p = 0.02). CONCLUSIONS: In type 1 diabetes coronary artery calcification is greatly increased in women and the gender difference in calcification is lost. Little of this is explained by known coronary risk factors.

Adult↗
PubMed2001

Assessing intraocular lens calcification in an animal model.

PURPOSE: To describe an animal model used to evaluate the propensity of various biomaterials to calcify intraocularly. SETTING: Research Department, Allergan Inc., Irvine, California, USA. METHODS: Intraocular lens (IOL) optic materials were implanted intramuscularly and/or subcutaneously in rabbits for up to 90 days. The materials included silicone, poly(methyl methacrylate) (PMMA), hydroxyethyl methacrylate hydrogel, and several hydrophobic acrylic materials. Scanning electron microscopy (SEM) and energy dispersive x-ray spectroscopy (EDS) were used to detect calcification demonstrated by characteristic discrete nodules containing both calcium and phosphate. Histological methods were used to evaluate tissue reactivity. Disc lenses fabricated from the experimental material were also bilaterally implanted in rabbit eyes that were monitored by slitlamp biomicroscopy. The lenses were explanted at 1, 2, 5.5, 10, and 20 months for SEM/EDS analysis. RESULTS: No calcification was noted in the intramuscularly or subcutaneously implanted silicone, PMMA, and acrylic optic materials. Calcification was noted on the intramuscularly, subcutaneously, and intraocularly implanted experimental acrylic and the intramuscularly implanted hydrogel material; the calcification was more extensive on the hydrogel. Signs that suggested intraocular calcification were first noted on the experimental IOLs at 4 months, but calcification was not confirmed until 10 months. CONCLUSIONS: Material calcification occurred more quickly in an intramuscular or subcutaneous environment than in an intraocular environment. Intramuscular and subcutaneous implantation appears to be an excellent model for screening materials for calcification potential. However, calcification is both host environment and material dependent. Using intramuscular or subcutaneous implantation in animal models to predict intraocular calcification in humans must be done with caution.

Acrylic Resins↗
PubMed2006

Artery calcification in uremic rats is increased by a low protein diet and prevented by treatment with ibandronate.

The present experiments investigate medial artery calcification in adult rats made uremic by feeding a synthetic diet containing 0.75% adenine for 4 weeks. Calcification was assessed by Alizarin red staining of intact aortas, by von Kossa staining of carotid artery sections, and by calcium and phosphate incorporated into the thoracic aorta. The major conclusions are as follows: Lowering the protein content of the diet from 25 to 2.5% dramatically increases the frequency and extent of medial artery calcification in uremic rats without significantly affecting the elevation in serum creatinine, phosphate, or parathyroid hormone. This observation suggests that low dietary protein intake could be a risk factor for medial artery calcification in uremic patients. Medial artery calcification in uremic rats is prevented by a dose of ibandronate that inhibits bone resorption. The observation suggests that bone resorption inhibitors could prevent artery calcification in uremic patients. Medial artery calcification in uremic rats correlates with increased serum bone Gla protein (BGP; osteocalcin), but not with serum matrix Gla protein or fetuin. This finding indicates that it could be of interest to examine the relation between serum BGP and artery calcification in uremic patients. Each of these conclusions lends support for our hypothesis that medial artery calcification is linked to bone resorption. Future investigations of the as yet unknown biochemical basis for this link will be facilitated by the present discovery that a synthetic, 2.5% protein diet containing 0.75% adenine produces consistent and dramatic medial calcification in adult rats within just 4 weeks.

Animals↗
PubMed2003

Coronary artery, aortic wall, and valvular calcification in nondialyzed individuals with type 2 diabetes and renal disease.

BACKGROUND: Individuals with end-stage renal disease (ESRD) have highly prevalent and severe vascular and valvular calcification. We undertook this study to test the hypothesis that vascular and valvular calcification begins and is often severe long before diabetic renal disease progresses to ESRD. METHODS: A total of 32 nondialyzed individuals with type 2 diabetes mellitus and diabetic renal disease (albumin excretion rate>30 microg/min) [mean glomerular filtration rate (GFR), 49.8 +/- 6.1 mL/min/1.73 m2] were identified and compared with a group of 18 normoalbuminuric diabetics. We used 3:1 matching to identify 95 nondiabetic controls without renal disease, matched for age, gender, ethnicity, and the presence/absence of dyslipidemia, hypertension, and known coronary artery disease (CAD). RESULTS: Using electron beam computed tomography (CT), the prevalence of coronary artery calcification was significantly greater among diabetic renal disease individuals (prevalence, 94% vs. 59%, P < 0.001; median score, 238 vs. 10, P < 0.001) than the nondiabetic controls. The coronary artery calcification scores were significantly more severe among diabetic renal disease individuals than either the diabetic or nondiabetic controls. Among individuals with diabetic renal disease, the coronary artery calcification and aortic wall calcification scores were several-fold greater among those with known CAD than among those without. There was also a significantly greater prevalence of aortic and mitral valve calcification among diabetic renal disease individuals than nondiabetic controls (aortic, 23% vs. 6%, P = 0.03; mitral, 25% vs. 2%, P < 0.001). Multivariate analysis using all three groups reproduced these findings and also consistently identified age and diabetic renal disease as additional predictors for the presence or severity of coronary artery and aortic wall calcification. CONCLUSION: In this first, systematic analysis among nondialyzed individuals with diabetic renal disease, these data demonstrate that vascular and valvular calcification is present and often severe long before the disease progresses to ESRD. The data also suggest that the coronary artery and aortic wall calcification may represent atherosclerosis.

Aortic Diseases↗
PubMed2002

Differences and similarities between patients with and without end-stage renal disease, with regard to location of intracardiac calcification.

It has been known for some time that mitral annulus calcification is common in end-stage renal disease (ESRD) patients on long-term dialysis, as well as in elderly patients without renal failure. However, a systematic comparison of cardiac calcification in these two types of patients has not yet been made. We examined two-dimensional echocardiograms in 33 patients with ESRD (mean age 66 +/- 10 years) and in 34 other patients with intracardiac calcification but no ESRD (mean age 69 +/- 9 years), with particular attention to precise anatomic location of calcification. Age was not significantly different in the two groups. The incidences of posterior mitral annulus calcification and aortic valve calcification were not significantly different in the ESRD and non-ESRD groups, though mitral annulus calcification tended to be larger in ESRD patients. Basal mitral leaflet calcification and papillary muscle calcification was much more common in the ESRD group. Calcification of intervalvar fibrosa and of tricuspid annulus were noted only in ESRD patients.

Aged↗
PubMed2001

Placental calcification: a metastatic process?

Placental calcification commonly increases with gestational age. The mechanism of apatite mineralization probably involves one of three known mechanisms of tissue calcification: physiological (like bone), dystrophic (ischaemia-related) or metastatic (mineralization in a supersaturated environment). This study was designed to determine the mechanism of calcification by examining (1) the mineral content of placental calcifications in comparison to other physiological and pathological apatites, and (2) the expression of bone morphogenetic proteins (BMPs), which are important in physiological calcification, across gestational age. By energy-dispersive x-ray analysis (EDXA), the Ca/P weight ratio for apatitic mineral from mature calcifications was 2.00+/-0.05 (s.e.), which is similar to that for stones formed in a metastatic, supersaturated environment and lower than that observed in physiological calcification. Biologically active BMP, which was determined by bioassay, was demonstrated in mature and postmature placentae. The BMPs PLAB, PDF and related protein INSL-4 were identified by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR), but their mRNA expression was independent of gestational age (7-41 weeks of gestation). We conclude that (1) the identified BMPs were not related directly to placental calcification, which argues against physiological calcification, and (2) the chemical composition of the apatitic mineral was suggestive of rapid formation in a supersaturated environment, which is consistent with a metastatic mechanism of calcification.

Animals↗
PubMed2000

Phosphorylation of osteopontin is required for inhibition of vascular smooth muscle cell calcification.

Osteopontin (OPN) is a non-collagenous, glycosylated phosphoprotein associated with biomineralization in osseous tissues, as well as ectopic calcification. We previously reported that osteopontin was co-localized with calcified deposits in atherosclerotic lesions, and that osteopontin potently inhibits calcium deposition in a human smooth muscle cell (HSMC) culture model of vascular calcification. In this report, the role of phosphorylation in osteopontin's mineralization inhibitory function was examined. The ability of OPN to inhibit calcification completely depended on post-translational modifications, since bacteria-derived recombinant OPN did not inhibit HSMC mineralization. Following casein kinase II treatment, phosphorylated OPN (P-OPN) dose-dependently inhibited calcification of HSMC cultured in vitro about as effectively as native OPN. The inhibitory effect of osteopontin depended on the extent of phosphorylation. To determine the specific structural domains of OPN important for inhibition of calcification, we compared OPN fragments (N-terminal, C-terminal, and full-length), and compared the inhibitory effect of both phosphorylated and non-phosphorylated fragments. While none of the non-phosphorylated OPN fragments effected calcification, P-OPN caused dose dependent inhibition of HSMC calcification. P-OPN was treated with alkaline phosphatase to create dephosphorylated OPN. Dephosphorylated OPN did not have an inhibitory effect on calcification. The expression of OPN mRNA and P-OPN secretion by HSMC were decreased in a time-dependent manner during culture calcification. These results indicate that phosphorylation is required for the inhibitory effect of OPN on HSMC calcification, and that regulation of OPN phosphorylation represents one way in which mineralization may be controlled by cells.

Alkaline Phosphatase↗
PubMed2004

Determinants of progressive vascular calcification in haemodialysis patients.

BACKGROUND: We determined recently that targeted treatment with calcium-based phosphate binders (calcium acetate and carbonate) led to progressive coronary artery and aortic calcification by electron beam tomography (EBT), while treatment with the non-calcium-containing phosphate binder, sevelamer, did not. Aside from the provision of calcium, we hypothesized that other factors might be related to the likelihood of progressive calcification in both or either treatment groups. METHODS: We explored potential determinants of progressive vascular calcification in 150 randomized study subjects who underwent EBT at baseline and at least once during follow-up (week 26 or 52). RESULTS: Among calcium-treated subjects, higher time-averaged concentrations of calcium, phosphorus and the calcium-phosphorus product were associated with more pronounced increases in EBT scores; no such associations were demonstrated in sevelamer-treated subjects. The relation between parathyroid hormone (PTH) and the progression of calcification was more complex. Lower PTH was associated with more extensive calcification in calcium-treated subjects, whereas higher PTH was associated with calcification in sevelamer-treated subjects. Serum albumin was inversely correlated with progression in aortic calcification. Sevelamer was associated with favourable effects on lipids, although the link between these effects and the observed attenuation in vascular calcification remains to be elucidated. CONCLUSION: Calcium-based phosphate binders are associated with progressive coronary artery and aortic calcification, especially when mineral metabolism is not well controlled. Calcium may directly or indirectly (via PTH) adversely influence the balance of skeletal and extraskeletal calcification in haemodialysis patients.

Aged↗
PubMed2004

Association of pelvic arterial calcification with arteriovenous thigh graft failure in haemodialysis patients.

BACKGROUND: Arterial calcification is a common problem in patients with chronic kidney disease, and has been associated with adverse clinical outcomes. The goal of the present study was to evaluate whether pelvic artery calcifications are associated with technical failure of arteriovenous thigh grafts in haemodialysis patients. METHODS: From 1 January 1999 to 30 June 2002, thigh grafts were placed in 54 haemodialysis patients who had exhausted all options for permanent vascular access in the upper extremities. Perioperative computed tomography (CT) of the abdomen and pelvis was obtained in 32 of the patients for diagnostic purposes unrelated to vascular access planning. Two radiologists, who were blinded to the graft outcomes, scored the vascular calcifications on CT of the distal aorta, common iliac, external iliac and common femoral arteries on a semi-quantitative 5-point scale. The association between technical graft failure (inability to complete the anastomosis) and the vascular calcification score was analysed. RESULTS: There was a high inter-observer agreement in scoring vascular calcification (kappa = 0.801). Among 26 patients with absent or mild pelvic arterial calcifications (grade 1-2) on CT, none (0%) experienced technical graft failure. In contrast, three of six patients (50%) with moderate to severe calcification (grade 3-5) had technical graft failures (P = 0.004 by Fisher's exact test). The cumulative 1 year graft patency was lower in the group with grade 3-5 calcification (33 vs 81%, P = 0.09). The two groups were similar in age, gender, race, diabetes, duration of dialysis, serum calcium, serum phosphorus and serum parathyroid hormone. CONCLUSION: There is a strong association between pelvic artery calcifications and technical failure of thigh grafts. The presence of moderate to severe vascular calcification is predictive of poor cumulative 1 year graft patency.

Arteries↗
PubMed2006

The impact of traditional and non-traditional risk factors on coronary calcification in pre-dialysis patients.

BACKGROUND: Coronary heart disease (CHD) is the leading cause of death among end-stage renal disease patients. There is evidence that coronary calcification is a marker of atherosclerotic vascular disease and is predictive of cardiovascular events, especially in patients on renal replacement therapy. It has recently been suggested that CHD begins in the pre-dialysis period. However, data regarding coronary calcification in this population is scarce. This study was aimed at evaluating such coronary calcification and identifying related factors. METHODS: A total of 96 chronic kidney disease out-patients who were not on dialysis were included. Patients presenting neoplastic, infectious or inflammatory diseases were excluded. Demographic characteristics, clinical profiles, laboratory test results and multislice computed tomography scans were evaluated. RESULTS: The median age was 55 years (range 20-69 years), 67% were men and the median creatinine clearance was 37 ml/min/1.73 m(2). Coronary calcification, defined as a coronary artery calcification score (CACS) >0 Agatston units (AU), was seen in 61 patients (median 89.1 AU, range 0.37-2299.3 AU). On average, these patients were older, more often had diabetes, higher body mass indices and higher Framingham risk indices, as well as presenting higher proteinuria, intact parathyroid hormone (iPTH), blood glucose and triglyceride levels compared with those without calcification. Multiple logistic regression analysis, adjusted for age and diabetes, identified iPTH and triglyceride levels as independent determinants of calcification. Severe calcification (CACS >400 AU) was seen in 22 patients, who were also older and more frequently had a history of cardiovascular disease (CVD), as well as having higher levels of phosphorus, blood glucose and soluble Fas (sFas). Multiple logistic regression analysis, adjusted for age and diabetes, identified phosphorus and sFas levels as independent determinants of severe coronary calcification. CONCLUSION: Coronary calcification is highly prevalent in pre-dialysis patients and correlates with traditional and non-traditional risk factors for CVD.

Adolescent↗