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PubMed2006

Serum osteoprotegerin in young survivors of myocardial infarction.

Osteoprotegerin (OPG) is a member of the tumour necrosis factor superfamily and is involved in the regulation of bone metabolism and vascular calcification. Increased serum OPG levels have been reported in patients with stable angina pectoris and survivors of myocardial infarction with heart failure. The purpose of the present study was to determine serum OPG levels in young survivors of acute myocardial infarction (MI), and the relationship between OPG, homocysteine, sCD40L and coagulation factors in blood. Fifty-eight patients with verified MI, 40-60 years of age, were recruited 1-4 years after the acute event into an age- and sex- matched case control study with controls recruited from the general population. Serum OPG levels were similar in cases (2.41 ng/ml, 2.11-2.77 ng/ml) (mean, 95% CI) and controls (2.43 ng/ml, 2.11-2.79 ng/ml) (p = 0.92). Significant correlation between OPG and homocysteine was found in patients (r = 0.30, p = 0.02) and controls (r = 0.35, p = 0.007). A significant negative correlation was found between OPG and sCD40L in patients (r = -0.51, p < 0.001), but not in controls (r = 0.001, p = 0.96). No associations were found between serum OPG and markers of coagulation activation. The present study shows that serum OPG level was not increased in young survivors of uncomplicated myocardial infarction. Serum OPG levels were not associated with thrombin generation assessed by thrombin-antithrombin complexes (TAT), but a positive association between serum OPG and homocysteine was found.

Adult↗
PubMedDate not supplied

[Is there any role predictable for bone morphogenetic protein-7 in nephrology?].

The existence of proteins with bone morphogenetic properties has been suggested for many years to explain the calcifying effect observed, with bone extracts, in ectopic tissues in vivo. Subsequently, at least thirty different proteins (identified as Bone Morphogenetic Proteins, BMPs) with this capacity have been discovered. The osteogenic activity of these substances is evident from the early phases of embryogenesis. However, besides bone, these proteins have been shown to affect other tissues too, where they affect cellular functions like proliferation, differentiation and apoptosis. They act through a specific receptor system partly shared with TGF-beta; in fact, they have been shown to inhibit TGF-beta actions. BMP-7 in particular is of vital importance in embryogenesis through its actions on bone, kidney and eyes, while in adulthood it is mainly expressed in the kidney, where specific receptors have been localized. BMP-7 has been successfully employed, for therapeutic purposes, in several animal models of nephropathies, where the most striking result is the constant reduction of fibrosis. Moreover, BMP-7 has been used successfully in experimental models of renal osteodystrophy and of vascular calcification. To date the only available human data are those obtained in orthopedy where BMP-7 has been successfully employed to induce the healing of pathologic fractures. Clinical data in nephropathic patients are therefore warranted to rule out the true value of this, very interesting, new molecule.

Bone Morphogenetic Protein 7↗
PubMed2006

[Bone and bone related biochemical examinations. Significance of measurement of serum calcium, phosphorus, alkaline phosphatase, corrected calcium and urine calcium].

Classical clinical calcium endocrinology was built on measurements of serum Ca, P and alkaline phosphatase as well as urinary Ca. Serum Ca, the most strictly maintained biological constant, occupies the central role among them, controlling PTH secretion and bone metabolism. Ca is strongly bound to proteins especially albumin, so that total serum Ca values are sometimes misleading, necessitating the use of corrected or ionized Ca. Serum Pi rises early in renal insufficiency, playing an important role in vascular calcification. Growth hormone and thyroid hormone functions are also reflected on serum P. Serum alkaline phosphatase especially the bone-specific type is also important for the evaluation of bone dynamics such as growth and tumor metastasis. These classical datasets should be reevaluated in the light of actions of new compounds such as calcimimetics, P-binders, bisphosphonates, vitamin D derivatives, cytokines, etc.

Alkaline Phosphatase↗
PubMed2006

[Bone and bone related biochemical examinations. Bone and collagen related metabolites. Measurement and clinical role of OPG].

Osteoprotegerin (OPG) has been identified as a novel cytokine that specifically inhibits osteoclastogenesis. OPG acts as a soluble decoy receptor that inhibits the binding of receptor activator of NF-kappaB ligand (RANKL) to its receptor RANK and thus inhibits the proliferation and activation of osteoclasts. Human serum OPG can now be easily measured using a sandwich-type ELISA kit, and the roles of OPG in various diseases have been revealed by clinical studies. These clinical studies have demonstrated that OPG plays an important role in not only metabolic bone diseases but also other diseases such as coronary artery disease, vascular calcification, chronic renal failure and malignancy. Furthermore, OPG may be a useful and novel marker related to the progression or mechanisms of these diseases.

Biomarkers↗
PubMed2006

[Fetuin A in children with renal diseases].

UNLABELLED: Fetuin A, 59 kDa protein, produced in the liver is a circulating inhibitor of vascular calcification. The aim of the study was to estimate a concentration of fetuin A in children with renal diseases. Fifty three children were examined: 18 with idiopathic nephrotic syndrome (NS) aged 2.5 to 14.5 years, mean 6.6 +/- 3.6 and 35 with chronic renal failure (CRF) aged 4.5 to 20 years, mean 13.3 +/- 3.9. The control group (K) consisted of 22 healthy children, aged from 6.5 to 17.5 years, mean 10.8 +/- 3.3. In all children serum concentration of fetuin A (ELISA method, BioVendor), calcium (sCa), phosphorus (sP), protein (P), albumin (Alb), total cholesterol (TC) and triglycerides (TG) were measured. The daily protein excretion in children with proteinuria (mg/kg/day) and the serum parathormone (PTH) level in children with CRF were analysed. RESULTS: The concentration of fetuin A was the lowest in children with NS (78.1 +/- 24.5 ng/ml) and was statistically different (p=0.0003) than in group K (101.4 +/- 11 ng/ml) and group CRF (106.7 +/- 13.7 ng/ml). In group NS significant correlations were found between concentrations of fetuin A and sCa (r=0.62, p<0.01), P (r=0.59, p= 0.01) and Alb (r=0.64, p<0.01) and negative correlations with concentration of TC (r=-0.68, p<0.01) and daily proteinuria (r=-0.79, p<0.001). In groups K and CRF the correlations of fetuin A level and analysed parameters were not found. CONCLUSION: Low concentration of fetuin A in children with nephrotic syndrome may be the additional agent to promote the atherogenic lesions.

Adolescent↗
PubMed2006

[Osteoprotegerin and calcium-phosphorus metabolism parameters in children with chronic renal failure].

UNLABELLED: Osteoprotegerin (OPG), a member of the TNF receptor superfamily is a natural inhibitor of osteoclastogenesis and important inhibitor of vascular calcification. The aim of the study was to estimate a correlation of serum OPG level and the other parameters calcium-phosphorus metabolism in children with chronic renal failure. Seventy four children with chronic renal insufficiency, 48 on conservative treatment (CRF) aged 13 +/- 3 years with creatinine clearance 45 +/- 21 ml/min/1.73m2 and 26 with end-stage renal disease (ESRD) aged 14 +/- 5 years were examined. The control group (K) consisted of 23 healthy children aged 10.8 +/- 3 years. In all children serum concentration of OPG, calcium (sCa), phosphorus (sP), PTH, CAP (cyclase activating PTH), CIP (cyclase inactive PTH) and osteocalcin (OC) were measured. OPG was determined by ELISA method (Biomedica), PTH and OC by IRMA (Duo-PTH, Scantibodies, USA and Osteo-Riact firm CIS, F). RESULTS: The concentration of OPG was higher in ESRD group (3 +/-1.6 pmol/l) than in K (1.95 +/- 0.56 pmol/l), p<0.005. The concentration of OPG in CRF group (2.42 +/- 1.4 pmol/l) was not different from this in K and ESRD. The concentration of OPG did not correlate with serum creatinine level. In CRF group no correlation was found between OPG level and the other parameters, in group ESRD the significant correlation between OPG and OC was found (R=0.55, p=0.006). The level of OPG in children CRF + ESRD correlated with PTH concentration (R=0.27, p<0.03), CAP (R=0.29, p<0.02), CIP (R=0.23, p<0.05) and OC (R=0.25, P<0.04). In patients with higher PTH level (> 200 pg/ml) the higher correlations between OPG and PTH, CAP and CIP were found. No significant correlation between PTH and OPG in patients with lower PTH level (< 200 pg/ ml) was found. No significant correlation between OPG and OC in patients with lower and higher PTH was found. CONCLUSION: The elevated levels of OPG in children with ESRD may reflect the higher bone turnover in these patients.

Adolescent↗
PubMed1990

The serum hormone levels, phosphate complex concentrations and enzyme activities in haemodialysed and kidney-transplanted children.

The serum hormone (T3, FT3, T4, FT4, TSH, hTG, a-hTG, GH, PTH, PRL, Cortisol) concentrations, the inorganic phosphate complexes (HPO2-4, H2PO-4, NaHPO-4, KHPO-4, CaHPO4, MgHPO4) and the enzyme activities (Amylase, Lipase, AP, ACE, GOT, GPT, psi-ChE, CK, gamma-GT, LDH) were investigated in 13 haemodialysed children, 7 kidney-transplanted children and in 15 healthy controls. This study confirmed that the kidney plays an important role in the metabolism of hormones. Prior to kidney transplantation 8 of the 11 tested hormone levels of haemodialysed children significantly differed from those of healthy controls, however, after kidney transplantation only two parameters did. The effect of dialysis is the least on the CaHPO4 complex among the different inorganic phosphate complexes. This may play a role in vascular calcification in chronic renal failure patients. The amylase and lipase activity were elevated in haemodialysed group, while in kidney-transplanted children the angiotensin converting enzyme (ACE) and alkaline phosphatase (AP) differed from those of the control group.

Adolescent↗
PubMed2006

[Chronic kidney disease-mineral and bone disorder (CKD-MBD)].

Changes in mineral and bone metabolism are prevalent in chronic kidney disease. There are several types of renal bone disease, called 'renal osteodystrophy (ROD)'. ROD includes osteitis fibrosa, osteomalacia, adynamic bone disorder, and mixed osteodystrophy. Osteitis fibrosa is high turnover bone due to secondary hyperparathyroidism. Osteomalacia is low turnover bone concomitant of increased osteoid. Adynamic bone disorder is low turnover bone due to excessive suppression of the parathyroid glands and recently represents the major bone lesion in dialysis patients. More recently, the term 'Chronic Kidney Disease-Mineral and Bone Disorder(CKD-MBD)' was proposed to describe the clinical syndrome that develops as a systemic disorder of mineral and bone metabolism due to chronic kidney disease such as vascular calcification.

Calcium Metabolism Disorders↗
PubMed2006

[Efficiency of total parathyroidectomy and autotransplantation in 31 patients with uremic hyperparathyroidism].

OBJECTIVE: To analyse the efficacy of total parathyroidectomy with autotransplantation (total PTX + AT) in treating uremic secondary hyperparathyroidism and to discuss the relevant medical treatment used. METHODS: The clinical data of 31 patients with uremic SHPT admitted into our hospital from 1996-2005 were analysed with respect to total PTX + AT. RESULTS: The period of hemodialysis were for the patients was on the average 9.2 years. There were 22 male and 9 female with an average age of 42.4 (31 - 67) years. The clinical manifestations consisted of osteoarticular pain in 83.9%, fractures in 35.5%, soft tissue and vascular calcification in 45.2% and pruritus in 80.6%. Laboratory examination yielded the following results: haematocrit 0.25 +/- 0.04, serum Ca (2.61 +/- 0.35) mmol/L, serum P (2.14 +/- 0.31) mmol/L, plasma total alkaline phosphatase (AKP) (885 +/- 335) U/L and parathyroid hormone (iPTH) (1811 +/- 879) ng/L (700 - 2500 ng/L). Cervical ultrasonography and/or emission computed tomography showed 2 - 4 hyperplastic glands. All of the patients showed no response to medical treatment including vitamin D. Total PTX + AT was performed on the 31 cases. Clinical symptoms and signs markedly improved after operation in 1 to 2 weeks. However, fracture and ectopic calcification showed no improvement. Plasma iPTH decreased rapidly (< 200 ng/L) postoperatively in 1 to 2 days. Serum Ca and P returned to normal. AKP was corrected in 1 to 3 months. CONCLUSION: Total parathyroidectomy with autotransplantation is an effective treatment for severe uremic secondary hyperparathyroidism patients.

Adult↗
PubMed1990

[Systemic calciphylaxis and acquired perforating disease in a uremic patient].

We show the case of a patient suffering from a chronic renal failure in hemodialysis. He had a ischemic necrosis that was quickly progressive in his fingers and toes. It was necessary to amputate them. Diffuse vascular calcifications were recorded so radiologically than pathologically. PTH and phosphocalcic product were raised. Parathyroidectomy was practised with a quick initial improvement but immediately new distal ischemic lesions and keratotic papules with histologic perforation, that became necrosed, appeared in his buttocks and inferior extremities. The coexistence of acquired perforating disease and calciphylaxis in uremic patients has not been reported until now.

Calciphylaxis↗
PubMed1989

Effect of hemodialysis on the distribution of phosphates in blood.

Phosphate retention is commonly associated with chronic renal failure. Previously we presented a technique to calculate the distribution of phosphate constituents in body fluids. We studied it in pre- and postdialysis serum of 62 patients. After hemodialysis, there was some decrease in the concentration of each constituent, with significant changes in the molar fraction of H2PO4- and CaHPO4. There is a significant negative correlation between the molecular mass of the constituent (X) and the effect of dialysis (Y): urea and H2PO4- 50%; NaHPO4-, HPO4(2-), and creatinine 41-44%; MgHPO4 39%, and CaHPO4 28%. Y = 69.7 - 0.26x, r = -0.833, p less than 0.001. This limited removal of CaHPO4 may contribute to the vascular calcification and peripheral ischemic necrosis of chronic uremic patients.

Adult↗
PubMed1988

Correlation of morphological variables in the coronary atherosclerotic plaque with clinical patterns of ischemic heart disease.

The frequency and severity of "morphological" variables (fibrosis, proteoglycan accumulation, atheroma, intimal vascularization, calcification, acute intimal hemorrhage, and both adventitial and intimal lymphoplasmacellular infiltrates) in atherosclerotic plaques were related to plaque type, percentage of lumen reduction, plaque length, and intimal and medial thickness in 3,640 coronary artery sections sampled at the site of maximal lumen reduction in 8 selected segments from 100 cases of acute myocardial infarct, 50 of chronic angina, 208 of unexpected sudden coronary death with or without prodromata, and from 97 normal subjects dying accidentally. Morphological variables were occasionally observed in 1,519 sections with no lumen reduction. They were found only in sections from ischemic patients. With increasing luminal stenosis and intimal thickness, progression of the coronary plaque seemed to start as a fibrous change followed by proteoglycan accumulation in the deeper portion of the fibrous intima. Proteoglycan deposits appeared as a recurrent phenomenon. In them, atheroma or calcification develop. Intimal hemorrhage was a less frequent variable. It was found mainly in a vessel supplying an infarcted area. Lymphoplasmacellular inflammation correlated mainly with proteoglycan accumulation and atheroma, both showing a parallel increase with increasing intimal thickness and lumen reduction. No correlation was found between plaque variables and sex, age, heart weight, and infarct size. Significant variations in the distribution of plaque variables were observed among hearts of patients in the ischemic groups and between them and controls. In particular, inflammatory reaction was significantly more frequent and severe in ischemic groups than in controls, independent of the degree of coronary stenosis. Coagulative myocytolysis (contraction band necrosis), found in the majority of ischemic patients, correlated with the inflammatory reaction in supplying vessels. A peculiar tropism of mononuclear cell infiltrates for adventitial nerve structures was found. As a result, we question whether this inflammation may trigger coronary spasm and/or coagulative myocytolysis ("active" plaque vs "inactive" plaque).

Arteries↗
PubMed1986

Controlled trial of calcitriol in hemodialysis patients.

We report on a 5-year, prospective, double-blind trial of 1,25 dihydroxycholecalciferol (calcitriol) versus placebo in 76 hemodialysis patients without biochemical or radiological evidence of bone disease. Calcitriol, 1 microgram daily, regularly induced hypercalcemia. Doses of 0.25 microgram daily or less proved satisfactory in most patients. During calcitriol treatment, plasma calcium concentration was significantly higher and serum parathyroid hormone concentration significantly lower than on placebo. There was no difference in the rates of development or of progression of vascular calcification in the two groups. Significantly more patients on placebo (17 vs. 6, p less than 0.05) developed a sustained elevation of plasma alkaline phosphatase concentration. Calcitriol appeared to protect against the development of histological evidence of osteitis fibrosa but not of osteomalacia, but accumulation of aluminum in bone occurred during the study. We conclude that calcitriol delays and may prevent the development of osteitis fibrosa in patients receiving regular hemodialysis and may reasonably be prescribed routinely in hemodialysis patients without biochemical or radiological abnormality, unless there is a substantial prospect of early renal transplantation.

Adolescent↗
PubMed1985

Cerebral atrophy in patients on long-term regular hemodialysis treatment.

The presence of Cerebral Atrophy in the form of cortical damage (Cortical Atrophy) or subcortical damage (enlargement of ventricular cavities) was explored by computed tomography (CT) scans in 30 patients maintained on regular hemodialysis treatment (RDT) for not less than 10 years, and less than 50 years of age. Whereas a group of 50 normal subjects of the same age, used as control, gave no evidence of cerebral atrophy, 46.6% of the patients maintained on RDT showed cortical atrophy, evenly diffuse in half the cases and predominantly frontal in the other half. In addition 16.6% of the patients showed subcortical atrophy, even in the absence of evident central neurologic or neuropsychic symptoms. In a search for the possible causes of this high incidence of cerebral atrophy in chronic hemodialysis patients we reviewed the last five years' profiles of clinical and blood biochemistry parameters known or suspected to produce brain damage when altered, as stored in a computer system available to our Hemodialysis Unit: these were mean blood pressure before and after hemodialysis, blood cholesterol and triglyceride assays, and mean daily oral intake of A1(OH)3. The status of arterial blood vessels in terms of vascular calcification in soft tissue roentgenograms was also defined; then we correlated these clinical and biochemical indices with the findings of cerebral CT scans by the Fisher test and Discriminant Analysis. The Fisher test revealed a decreasing correlation of cerebral atrophy with mean blood pressure, A1(OH)3 intake, blood cholesterol content, arterial calcifications and blood trygliceride assay in that order.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1979

[The hand in diabetes. Study of 97 diabetics compared to a control group].

To determine whether there is hand involvement specific to diabetes, 97 diabetics were compared with the same number of matched controls. Hands were examined with particular emphasis on skin, intrinsic muscles, articular mobility, sense of touch and vibration, digital systolic pressure, and radiological analysis of bones and joints. The most significant involvement, clearly present in 7 cases and less specifically in 12 other diabetics, included all of the following: atrophy and weakness of intrinsic muscles, painful interphalangeal rigidity limiting extension or flexion of the fingers, periarticular swelling of the phalanges, and trophic changes of the skin. Separately, these changes are not specific to diabetes: in the control group, although less frequent, they were found in patients aged 60 and over and are considered to be signs of senescence. Diabetes apparently accelerates the process of aging. Diabetic changes in the hand appear to be facilitated by neuropathy but not by arterial involvement. X-ray revealed a higher incidence of osteopenia and above all of vascular calcifications in the diabetic.

Adult↗
PubMed1979

The feet in diabetes. Roentgenologic observation in 1501 cases.

The manifestations of diabetic osteoarthropathy are described. Computerized analysis of the films of the feet of 1501 diabetic patients showed one or more lesions in 55% of patients. Exostosis (36%), vascular calcifications (25%) and osteoporosis (12.2%) are by far the most frequent symptoms. Geodes (3.7%), destructive lesions (3.9%), sclerosis (4%) and articular lesions (5.1%) are second in frequency. Osteolytic lesions and reconstruction showed a high female predominance, whereas sclerosis is predominant in males (61.6--38.4%).

Diabetes Complications↗
PubMed1983

Surgical treatment of secondary hyperparathyroidism.

Secondary hyperparathyroidism is a recognized complication which develops in patients on hemodialysis for chronic renal failure. Parathyroidectomy may be required in patients with severe renal osteodystrophy, intractable pruritus, soft tissue and vascular calcifications or neuromuscular abnormalities. Three different operations have been employed in the treatment of patients with secondary hyperparathyroidism: total parathyroidectomy, radical subtotal (3 1/2 gland) parathyroidectomy and total parathyroidectomy with heterotopic autotransplantation. The last technique has been the procedure of choice in our group because the parathyroid mass is effectively reduced, and the results are comparable to those obtained with other techniques. Furthermore, the complication of graft dependent hyperparathyroidism, should it develop, can be managed by excising a portion of the transplanted tissue under local anesthesia.

Child↗
PubMedDate not supplied

[The hand of the patient under periodic hemodialysis treatment. Comparative radiographic and xeroradiographic aspects].

Renal osteodystrophy is the skeletal response to long-standing chronic renal disease. The radiographic features include hyperparathyroidism (osteitis fibrosa cystica), rickets or osteomalacia, osteoporosis, osteosclerosis and soft tissue and vascular calcifications. Many investigators have verified that changes in the phalanges of the hand are the most sensitive indicator of renal osteodystrophy, especially subperiosteal bone resorption. The hands of 50 chronic dialysis patients were evaluated for at least one year for tuftal resorption (acro-osteolysis), subperiosteal and intracortical bone resorption, and periosteal new bone formation (periosteal neostosis), using fine detail radiography and optical magnification. At last control, only in a group of 17 subjects (34%), xeroradiography of the hand was also performed. Results indicate the importance of the use of fine detail radiography in the early diagnosis of renal osteodystrophy and that serial radiography of the hand is a proper method of evaluating progressive bone resorption. In addition, a significant difference (p less than 0.05) is demonstrated between xeroradiography and radiography to evaluate periosteal neostosis.

Adult↗