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Hemodialysis access placement with preoperative noninvasive vascular mapping: comparison between patients with and without diabetes.

We retrospectively analyzed data on preoperative vascular mapping in 195 consecutive patients to investigate the common belief that patients with diabetes are poor candidates to have an arteriovenous fistula placed as dialysis access because they lack suitable blood vessels. There was no difference in venous diameter, arterial diameter, and arterial peak systolic velocity measurements between patients with and without diabetes. Patients with diabetes had a greater prevalence of vascular calcifications and greater cuff measurements of systolic segmental arterial pressure. In 140 of 195 patients, subsequent vascular access surgery had been performed in our institution, and 127 of these patients were on hemodialysis therapy at the end of the study period. There was no difference in the prevalence of fistula placement (66% versus 60%; chi-square = 2.6; df = 2; P = 0.28, not significant [NS]) and percentage of functioning fistulae between patients with and without diabetes (67% versus 62%; chi-square = 0.27; df = 1; P = 0.61, NS). The percentage of patients dialyzed through a temporary catheter was equal in patients with and without diabetes (18%). In summary, patients with diabetes seem to be as good candidates for arteriovenous fistula placement as patients without diabetes. Additional studies are required to determine the long-term outcome of fistulae in patients with diabetes.

Arteries↗

[Regulation of calcification by bisphosphonates].

Etidronate, an analogue of first generation of bisphosphonates, has inhibitory actions on mineralization and hydroxyapatite crystal formation, which is therefore used as a drug to treat ectopic ossification in cases with total hip arthroplasty and spinal cord injury. The effect of bisphosphonates to prevent calcification could be associated with the physical property to attach tightly to hydroxyapatite crystals in bone matrix. A recent investigation suggested that bisphosphonates might prevent arterial calcification through a mechanism associated with the enhanced production of parathyroid hormone-related peptide from vascular smooth muscle cells. A derivative of bisphosphonates to inhibit vascular calcification in atherosclerosis is expected and should be developed in the near future.

Animals↗

Novel cardiovascular risk factors in end-stage renal disease.

Traditional risk factors only in part explain the risk differential between the general population and the population of patients with chronic nephropathies. Uncontrolled hyperphosphatemia and high calcium phosphate product constitute risk factors for cardiovascular calcifications, cardiac ischemia, and adverse cardiovascular outcomes, yet inflammation may be an even more important trigger of vascular calcification than these metabolic derangements. Homocysteine predicts cardiovascular events in ESRD, but evidence that this sulfur amino acid is directly implicated in the high cardiovascular mortality of uremic patients is still lacking. It seems unlikely that Chlamydia pneumoniae is a major risk factor in dialysis patients because the association between anti-Chlamydia antibodies and incident cardiovascular events seems to depend largely on the confounding effect of some traditional risk factors. Oxidative stress and raised plasma concentration of asymmetric dimethylarginine (ADMA) are pervasive in ESRD, and high ADMA in these patients may be at least in part the expression of the high rate of generation of oxidants. ADMA per se seems responsible for a 52% increase in the risk of death and for a 34% increase in the risk of cardiovascular events in dialysis patients.

Arginine↗

Beneficial effects of vitamins D and K on the elastic properties of the vessel wall in postmenopausal women: a follow-up study.

Matrix-Gla Protein (MGP) is a strong inhibitor of vascular calcification, the expression of which is vitamin D dependent. MGP contains five gamma-carboxyglutamic acid (Gla)-residues which are formed in a vitamin K-dependent carboxylation step and which are essential for its function. Hence vascular vitamin K-deficiency will result in undercarboxylated, inactive MGP which is a potential risk factor for calcification. In the present study we describe the effects of vitamin K1 and D supplementation on vascular properties in postmenopausal women. In a randomized placebo-controlled intervention study, 181 postmenopausal women were given either a placebo or a supplement containing minerals and vitamin D (MD-group), or the same supplement with vitamin K1 (MDK-group). 150 participants completed the study and analysis was performed on 108 participants. At baseline and after three years, vessel wall characteristics, including compliance coefficient (CC), distensibility coefficient (DC), intima-media thickness (IMT) and the Young's Modulus (E) were measured to assess the effect of the supplements on the change of these parameters. The results showed that the elastic properties of the common carotid artery in the MDK-group remained unchanged over the three-year period, but decreased in the MD- and placebo-group. Comparing the MDK- and placebo-group, there were significant differences in decrease of DC (8.8%; p<0.05), CC (8.6%; p<0.05), and in increase of PP (6.3%; p<0.05) and E (13.2%, p<0.01). There were no significant differences between the MD-group and placebo. No significant differences were observed in the change of IMT between the three groups. It is concluded that a supplement containing vitamins K1 and D has a beneficial effect on the elastic properties of the arterial vessel wall.

Biomechanical Phenomena↗

Elastin-derived peptides and TGF-beta1 induce osteogenic responses in smooth muscle cells.

Elastin degradation associated with matrix metalloproteinase activity is a cell-mediated process, observed in almost all types of vascular calcification. In this study, we tested the hypothesis that elastin-derived peptides induce an osteogenic response in vascular smooth muscle cells (SMCs) in vitro. Using RT-PCR and specific protein assays, we demonstrated that rat aortic SMCs incubated with elastin peptides exhibited an increased expression of the 67 kDa elastin laminin receptor (ELR) and matrix metalloproteinase-2 and typical bone proteins, such as core binding factor alpha-1, osteocalcin, and alkaline phosphatase. The osteogenic gene expression in SMCs was further enhanced by the addition of TGF-beta1 along with the elastin peptides, in the absence of any other mineralizing agent. Conversely, lactose (an ELR antagonist) down-regulated expression of most investigated proteins. In conclusion, elastin-derived peptides and TGF-beta1 up-regulate the expression of typical bone proteins in cultured rat aortic SMCs, possibly via the ELR signaling.

Animals↗

The mechanisms of uremic serum-induced expression of bone matrix proteins in bovine vascular smooth muscle cells.

We have previously found that uremic human serum upregulates RUNX2 in vascular smooth muscle cells (VSMCs), and that RUNX2 is upregulated in areas of vascular calcification in vivo. To confirm the role of RUNX2, we transiently transfected a dominant-negative RUNX2 (DeltaRUNX2) construct in bovine vascular smooth muscle cells (BVSMCs). Blocking RUNX2 transcriptional activity significantly decreased uremic serum induced alkaline phosphatase (ALP) activity (268+/-34 vs 188+/-9.5 U/g protein, P<0.05) and osteocalcin expression (172+/-17 vs 125+/-9 ODU, P<0.05). To determine the mechanism by which uremic serum upregulates RUNX2, we examined cell signaling pathways. BVSMCs were incubated in the presence or absence of inhibitors and RUNX2 expression and ALP activity were determined. The results demonstrate that the cyclic AMP (cAMP)/protein kinase A (PKA), but not protein kinase C, signaling pathway is involved in uremic serum-induced RUNX2 expression and ALP activity in BVSMCs. To examine potential uremic 'toxins', we measured bone morphogenetic protein (BMP)-2 concentration and found that uremic serum contained increased BMP-2 (uremic serum=169+/-33 pg/ml, normal serum=117+/-15 pg/ml, P<0.05). The incubation of BVSMCs with noggin, an inhibitor of BMP, decreased RUNX2 expression. In addition, BMP-2 secretion progressively increased during calcification and uremic serum enhanced its secretion compared to normal serum. In conclusion, this study demonstrates that RUNX2 transcriptional activity is critical in uremic serum-induced bone matrix protein expression in BVSMCs and that the cAMP/PKA pathway is involved. BMP-2 is also increased in uremic serum and can upregulate RUNX2 and calcification in vitro in VSMCs.

Alkaline Phosphatase↗

Cutaneous calcification in patients with end-stage renal disease: a regulated process associated with in situ osteopontin expression.

BACKGROUND: Cutaneous calcification, or calcinosis cutis (CC), is found in approximately 1% of patients with end-stage renal disease (ESRD) undergoing chronic dialysis. While the pathogenesis is not well understood, it may be similar to those for medial and intimal vascular calcifications, which are actively regulated processes. OBSERVATION: In a retrospective study of 9 patients, the role of an active calcification process leading to CC was assessed by the immunohistochemical detection of osteopontin, which is a regulator of osseous and extra-osseous calcification processes. Calcinosis cutis was associated with female sex, vascular comorbidity, inconstant secondary hyperparathyroidism, and elevated levels of plasma calcium-phosphorus product. Six patients had a favorable outcome after the lowering of plasma calcium levels during dialysis or after parathyroidectomy. CONCLUSIONS: Calcinosis of the vascular media of subcutaneous vessels was the most common histologic feature and was always associated with osteopontin staining, suggesting that CC is a regulated process. Moreover, to our knowledge, extravascular staining of osteopontin in sweat glands, nerves, and macrophages was demonstrated for the first time in this study.

Adult↗

Massive left atrial calcification and devastating systemic emboli in a patient with chronic renal failure.

Valvular calcification is a common consequence of systemic calcium deposition resulting from chronic renal failure. Thrombi can form on such vascular calcifications and embolize to the cerebral, myocardial, and mesenteric vasculature with devastating consequences. We report the unique case of a patient with myocardial and cerebrovascular ischemia resulting from emboli arising from a massive mitral annular calcification.

Adult↗

New prospects for the management of renal bone disease.

The last decade has been a remarkably productive one in the field of bone biology. New insights into the maintenance of a normal bone microenvironment have led to significant advances in our understanding of many important skeletal disorders, including renal osteodystrophy. Novel targets for therapeutic manipulation have been exposed and encouraging progress made towards new treatments. In addition, just as clinical studies have alerted us to the potential hazards of vascular calcification, basic science has unearthed the intimate nature of the relationship between the previously separate disciplines of bone and vascular biology. The clinical nephrologist, however, may be forgiven a little cynicism at this point. If such progress has been made, why do the same proverbial difficulties confront us in day-to-day practice? Control of phosphate remains inadequate, despite a literature which constantly reaffirms its crucial importance, and parathyroid hyperplasia seems inevitable in many patients. Furthermore, even the satisfaction of successful control of serum parathyroid hormone concentration must now be tempered by disquiet regarding the skeletal and cardiovascular consequences of oversuppression. This review aims to provide an update of the latest developments in relevant skeletal research and to assess how recently acquired knowledge may improve clinical nephrological practice over the next five years.

Animals↗

Semitransparent volume-rendering CT angiography for lesion display in aortoiliac arteriosclerotic disease.

PURPOSE: The potential of semitransparent volume-rendering (STVR) computed tomographic (CT) angiography was evaluated for the assessment of hemodynamically significant stenoses in aortoiliac arteriosclerotic disease. MATERIALS AND METHODS: In a prospective study, 76 patients (57 men, 19 women; mean age, 70 years) underwent single-detector (n = 26) or multidetector (n = 50) CT angiography of the aortoiliac region. Intraarterial digital subtraction angiography (DSA) was performed in each patient. STVR images with semitransparent display of arterial lumen (opacity, 50%) and vascular calcifications (opacity, 20%), as well as maximum-intensity projection (MIP), frontal/sagittal curved planar reformation (CPR), and MIP/axial studies were independently reviewed for hemodynamically significant lesions (> or =70% cross-sectional area reduction). DSA combined with invasive pressure measurement was used as the standard of reference. Vessel wall calcifications were classified according to a four-point scale (0, not calcified; 1, mildly calcified; 2, moderately calcified; 3, severely calcified). RESULTS: Of the 380 reviewed vessel sections, 28 represented 70%-99% stenoses and 14 represented occlusions. For detecting >/==" BORDER="0">70% lesions, STVR as well as CPR and MIP/axial studies revealed significantly higher specificity (91%-94%), positive predictive value (PPV; 0.62-0.72), and accuracy (90%-94%) than MIP (specificity, 59%; PPV, 0.27; accuracy, 64%; P <.001) in moderately or severely calcified vessel sections. In noncalcified or mildly calcified sections, the specificity of MIP was comparable with the other rendering techniques (96%-98%; P values ranging from.34 to.77). No significant sensitivity differences were noticed among the CT angiography modalities: STVR, 79%; MIP, 88%; CPR, 83%; and MIP/axial, 93% (P values ranging from.12 to.78). Negative predictive values ranged from 0.97 to 0.99 (P values ranging from.14 to 1). Median calcification scores in sections with overestimated lumen narrowings were significantly higher (3, severely calcified) than in sections with correctly graded lumen width (1, mildly calcified) with all CT angiography modalities (P <.05). CONCLUSION: With use of STVR, visualization of vascular lumen can be improved by rendering highly transparent mural calcifications. Hence, for three-dimensional presentation of aortoiliac arteriosclerotic disease, STVR studies should be preferred to MIPs as supplements to review of axial-source images.

Aged↗

CT evaluation of renovascular disease.

Computed tomography (CT) plays an important role in evaluation and management of primary renovascular disease. Nonenhanced CT is useful for demonstrating renal hemorrhage, renal parenchymal or vascular calcifications, and masses. Contrast material-enhanced CT is essential to identify global or regional nephrographic abnormalities resulting from the vascular process (eg, renal infarcts, ischemia secondary to renal artery stenosis, arteriovenous communications). In addition, renal manifestations of a systemic disease (eg, vasculitis, thromboembolic disease) can be seen at CT. In trauma, occlusion of the main renal artery can be accurately diagnosed with contrast-enhanced CT. In cases of spontaneous renal hemorrhage without an apparent cause (eg, vasculitis, coagulopathy), a careful CT study should be performed to exclude renal cell carcinoma. The presence of fat in a hemorrhagic renal mass larger than 4 cm in diameter is characteristic of angiomyolipoma complicated by hemorrhage. Acute renal vein thrombosis appears as a clot in a distended renal vein, whereas renal vein retraction with collateral vessels is highly indicative of chronic thrombosis. Helical CT, especially with multiplanar two-dimensional and three-dimensional reconstruction following an intravenous injection of iodinated contrast material, has greatly improved our ability to directly image the proximal renal arteries and detect vascular lesions.

Diagnosis, Differential↗

Carotid transposition: another cause of wide retropharyngeal soft tissues.

OBJECTIVE: The purpose of this original report is to describe medial transposition of the common carotid arteries. This transposition may produce wide retropharyngeal soft tissues on lateral cervical radiographs. CONCLUSION: When common carotid arteries are transposed from their normal lateral positions into the retropharyngeal soft tissues, if vascular calcifications are present, this carotid abnormality is easily recognized on plain radiographs. Radiologists and clinical physicians should be aware that vascular transposition may be a benign cause of widening of the retropharyngeal soft tissues.

Aged↗

Clinical features of 24 patients on regular hemodialysis treatment (RDT) for 16-23 years in a single unit.

Careful investigation of the clinical conditions of patients on maintenance hemodialysis for about 20 years in a single dialysis unit was of great interest for evaluation of the pathological consequences in long-term survivors of insufficient correction of uremia and of the dialysis treatment "per se". We analyzed the outcomes for a cohort of 116 patients who started RDT before 1976 and the clinical conditions of the 24 patients still on RDT in our unit at the end of 1991 (average duration of treatment = 222 +/- 23 months). Actuarial survival was 72% at 10 years and 43% at 20 years. Rehabilitation of the 24 survivors was rather good: 13 were able to work, 8 were retired or unable to work, but able to care for most personal needs. Actual body weight, anthropometric parameters and biochemical parameters revealed a well-preserved nutritional status. Anemia improved from 23 +/- 7 at the start of RDT to 31 +/- 8 in the 21 patients never treated with erythropoietin. Blood pressure was normal without therapy in 18 patients and elevated in 6. Mild-to-moderate left ventricular hypertrophy was present in all the 6 patients with arterial hypertension and in only 6 of the 18 normotensive patients. The ratio of early diastolic filling to filling during atrial contraction (E/A ratio) was < 1 in 16 patients: it was 1.05 +/- 0.43 in 9 patients with stable intradialysis blood pressure and significantly lower (0.73 +/- 0.15) in 12 patients with recurrent intradialysis hypotension. Supraventricular arrhythmias were detected by Holter monitoring in 41% and ventricular arrhythmias in 35% of patients. Extensive vascular calcifications were present (in 100% of patients in the abdominal aorta), but only 4 patients showed clinical signs of peripheral vascular disease. Subperiosteal resorption was detected radiologically in the hands of 59% of patients. Bone histology, interpretable for only 20 patients, revealed no bone lesions in 1 case (5%), mild mixed osteodystrophy in 3 cases (15%), advanced mixed osteodystrophy in 5 cases (25%), osteodystrophy with predominant hyperparathyroidism in 2 cases (10%), osteodystrophy with predominant osteomalacia in 6 cases (30%), and aplastic bone disease in 3 cases (15%). Moderate aluminum staining was found in only 4 patients and was more marked in earlier biopsies taken before withdrawal of the aluminium-containing phosphate-binding drugs.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

[Arterial calcification:animal models].

The clinical significance of arterial calcification will continue to grow as the population ages. There is no appropriate animal model required to develop drugs to prevent vascular calcification. Several murine knockout models of some genes have led to new insights into the pathogenesis of arterial calcification. Good animal models can contribute to research progress in this area.

English Abstract↗

Coronary artery calcification, common carotid artery intima-media thickness and aortic pulse wave velocity in patients on peritoneal dialysis.

An increasing body of evidence suggests that atherosclerosis in patients with uremia differs from that found in general population in terms of advancement and localization of vascular lesions. It has also been suggested that different non-invasive techniques of vascular system evaluation are designed to show different types of lesions (i.e. vascular calcification, stiffness or 'classical' atherosclerosis). The aim of the study was to search for possible associations between results obtained with three different non-invasive methods of vascular system assessment in three different vascular sites in patients treated with peritoneal dialysis (PD). 61 patients (28 F, 33 M), mean age of 50.4+/-13.6 years, on maintenance PD for a median period of 10 months (range 1-96 months) were included. Coronary artery disease (CAD) was present in 21 subjects. In all subjects coronary artery calcification score (CaSc) using multi-row spiral computed tomography (MSCT), aortic pulse wave velocity (AoPWV) and ultrasound-based common carotid artery intima-media thickness (CCA-IMT) were performed as methods for assessing coronary calcium burden, arterial stiffness and atherosclerosis, respectively. Median value of CaSc equaled 11.5 Agatston units (range 0-5502.8 units). Median AoPWV was 10.4 m/s (range 7.56-18.1 m/s), and median CCA-IMT-0.6 mm (range 0.3-1.0 mm). In 16 patients (26.2%) at least one plaque in at least one common carotid artery was found on ultrasound. CaSc correlated with AoPWV (R=0.32, p<0.01) and with CCA-IMT (R=0.35, p<0.005), whereas no association was found between AoPWV and CCA-IMT. AoPWV, but not CaSc nor IMT correlated with blood pressure. The values of CCA-IMT and AoPWV increased together with consecutive Agatston categories (with p<0.001 for differences in AoPWV and p<0.05 for CCA-IMT). Patients with at least one plaque found in at least one CCA and patients with CAD were characterized with significantly higher values of CaSc, IMT and PWV, when compared to plaque-free and CAD- negative subjects, respectively. Association between CaSc and both IMT and PWV may suggest that the mechanism of three assessed vascular pathologies may be based, to some extent, on the process of pathologic calcium-phosphate deposition. Lack of correlation found between PWV and IMT may suggest that aortic stiffness and carotid atherosclerosis may partially differ in their pathologic background and/or are dissociated in time.

Aorta↗

Hyperhomocysteinaemia and aortic calcification are associated with fractures in patients on haemodialysis.

BACKGROUND: Fractures and atherosclerosis are common in patients with renal failure; this may be due to hyperhomocysteinemia. AIM: To examine the relationships between fractures, vascular calcification and homocysteine levels in haemodialysis patients. DESIGN: Cross-sectional survey. METHODS: We enrolled 37 men and 15 women who had been on haemodialysis for at least 1 year. We identified prevalent spine fractures by radiographs. Non-spine fractures were identified by self-report and confirmed by review of radiographs or radiology reports. We classified the presence and severity of lumbar aortic calcifications with lateral lumbar radiographs. We measured serum homocysteine in all subjects within 30 days of study entry. RESULTS: After adjusting for age and weight, increased levels of homocysteine were associated with an increased risk fracture (OR per mmol/l increase in homocysteine 1.6, 95%CI 1.2-2.0), as was the presence of aortic calcification (OR 1.6, 95%CI 1.2-2.1). Homocysteine and lumbar aortic calcification were highly correlated (r = 0.86). DISCUSSION: Hyperhomocysteinaemia may explain the relationship between fractures and atherosclerosis in patients with renal failure.

Aged↗

Vascular occlusions detected by magnetic resonance imaging.

Early experience with magnetic resonance imaging (MRI) indicates that it is well suited as a noninvasive vascular imaging modality. Blood flow at physiologic velocities results in a low signal within the vessel lumen and this property allows the separation of flowing blood from surrounding soft tissues. While flow effects, aneurysms, and mural lesions have been emphasized in the literature, vascular occlusions have received less attention. We evaluated 21 patients with documented venous or arterial occlusions on a 0.12-T developmental resistive unit. Venous occlusions caused by thrombus generally appeared as focal regions of increased signal. In 3 of 10 cases the venous thrombus itself could not be identified but the absence of a low-signal lumen in a normal location confirmed the impression of thrombus. In 2 of 17 venous occlusions a rim of low signal was noted around the thrombus. Venous collaterals were commonly seen. Tumor thrombus tended to have signal characteristics similar to the main bulk of the tumor from which it arose. There were four arterial occlusions including two cases of emboli, one arteriosclerotic occlusion, and one case of tumor invasion. Vascular calcifications, clearly evident on plain radiographs, were not seen on MRI. MRI appears to be a potentially useful noninvasive means of detecting vascular occlusions.

Adolescent↗

Novel aspects on RANK ligand and osteoprotegerin in osteoporosis and vascular disease.

The clinical coincidence of osteoporosis and vascular disease has long indicated that common mediators may adversely affect bone metabolism and vascular integrity alike. Receptor activator of NF-kappaB ligand (RANKL) is an important cytokine for bone resorption that acts through its osteoclastic receptor, receptor activator of NF-kappaB (RANK), while osteoprotegerin serves as a decoy receptor that binds RANKL and prevents activation of RANK. Skeletal and vascular cells are sources and targets of RANKL and OPG both in vitro and in vivo. Modulation of the RANKL/RANK/OPG system in animals results in a skeletal and vascular phenotype, and administration of OPG may prevent osteoporosis and vascular calcification. Recent studies on OPG serum levels and gene polymorphisms also suggest an important role of this cytokine system in skeletal and vascular diseases. In summary, there is increasing evidence that RANKL and OPG may link the skeletal with the vascular system.

Animals↗