Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Vascular Calcification”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources
PubMed2000

Expression of mineralisation-regulating proteins in association with human vascular calcification.

OBJECTIVES: These studies aim to investigate the expression and function of mineralisation-regulating proteins in association with human vascular calcification focussing on the similarities and differences between the two major calcification pathologies in man: atherosclerotic, intimal calcification and Monckeberg's sclerotic medial calcification. BACKGROUND: A number of studies have documented expression of mineralisation-regulating proteins in association with human atherosclerotic calcification leading to the suggestion that human vascular calcification may be a regulated process with similarities to developmental osteogenesis. METHODS: In situ hybridisation, immunohistochemistry and semi-quantitative RT-PCR analysis were used to determine the temporal and spatial expression patterns of mineralisation-regulating proteins within human calcified vascular lesions. Additionally, the expression and regulation of bone-associated proteins was analysed during spontaneous calcification of human VSMCs in vitro. RESULTS: In association with both medial and intimal calcification, the temporal changes in expression of mineralisation-regulating proteins are similar. Some constitutively expressed bone-associated proteins, including matrix Gla protein (MGP), are down-regulated in association with calcification while expression of a number of bone-associated proteins, not normally expressed in the vessel wall, are induced including alkaline phosphatase (ALK), bone sialoprotein (BSP) and bone Gla protein (BGP). In medial calcification the source of expression of these mineralisation-regulating proteins is VSMCs while in intimal lesions both VSMCs and macrophages express them. Furthermore, these bone-associated proteins are spontaneously expressed by VSMCs in vitro suggesting that human VSMCs are capable of simultaneously exhibiting smooth muscle and osteogenic-like properties. CONCLUSIONS: These studies imply that both medial and intimal vascular calcification are regulated processes; however the aetiology of each pathology differs.

Alkaline Phosphatase↗
PubMed2003

The progression of vascular calcification and serum osteoprotegerin levels in patients on long-term hemodialysis.

BACKGROUND: The aortic calcification index (ACI), estimated on abdominal computed tomographic scans, has been associated with the extent of arteriosclerosis in hemodialysis patients. However, the contribution of biochemical markers to the progression of vascular calcification in patients undergoing hemodialysis is not fully understood. METHODS: We examined the relationship between coronary risk factors; metabolic factors, including serum osteoprotegerin (OPG) concentration; and progression of vascular calcification in 26 dialysis patients. RESULTS: Mean patient age was 52.6 +/- 8.7 (SD) years, and mean duration of dialysis therapy was 7.7 +/- 5.8 years. ACI was measured twice in each patient, and the mean interscan period was 4.9 +/- 0.3 years. Mean ACI changed from 22.2 +/- 24.2 to 33.9 +/- 28.8 overall, and mean change in ACI (DeltaACI) was 12.0 +/- 9.9. Patients were divided into 2 groups: slow progressors, with DeltaACI of 4.1 +/- 3.2 (n = 13), and rapid progressors, with DeltaACI of 19.8 +/- 7.9 (n = 13). Serum fasting glucose and CRP levels of rapid progressors were high, and their serum albumin and intact parathyroid hormone levels were low. Multiple regression analyses showed that serum OPG levels were independently associated with vascular calcification in the hemodialysis patients studied. CONCLUSION: Rapid progression of vascular calcification was associated with dose of calcium carbonate prescribed and serum OPG concentration. The clinical significance of these observations remains to be determined.

Aortic Diseases↗
PubMed2005

A first approach to in vitro simulation of vascular calcification by the controlled crystallization of poorly crystalline calcium phosphates onto porous cholesterol.

A first approach to in vitro simulation of vascular calcification was elaborated. Vascular calcification was simulated by a slow crystallization of a non-stoichiometric poorly crystallized carbonateapatite from Kokubo's revised simulated body fluid (rSBF) on the surface of a porous pellet made of pure cholesterol. To achieve this, the crystallization experiments were performed under strictly controlled conditions (similar to physiological ones) provided by a constant-composition double-diffusion (CCDD) device. To obtain an even closer match to in vivo conditions, rSBF was enriched by the addition of glucose and bovine serum albumin (BSA) in physiological amounts. Precipitation took place on the surface of cholesterol and the precipitates consisted of poorly crystalline non-stoichiometric, sodium- and magnesium-containing carbonateapatite.

Animals↗
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↗
PubMed2004

Vascular calcification in patients with end-stage renal disease.

Vascular calcification is the most common type of extra-osseous calcification in end-stage renal disease (ESRD), manifesting as both medial and intimal calcification of large arteries. It is highly prevalent, often progressive and is associated with reduced arterial elasticity and increased mortality. Risk factors for calcification in ESRD include age, duration of dialysis, diabetes mellitus, most probably an elevated calcium-phosphorus product (Ca x P) level, the dose of calcium-containing phosphate binders and the induction of the systemic inflammatory response. Uraemic calcification was thought to be a largely physico-chemical process facilitated by elevated Ca x P (i.e. "metastatic" calcification). It is now well established, however, that vascular smooth muscle cells actively take up phosphate to form bioapatite. This process is associated with a phenotypic transformation of vascular smooth muscle cells during which they express osteoblast markers. In addition to phosphate, various other factors are likely to increase bioapatite formation, e.g. lipids and inflammatory cytokines. There have also been relatively new insights relating to the role of endogenous inhibitors of calcification [i.e. matrix Gla protein and fetuin-A (alpha(2)-Heremans-Schmid glycoprotein)], in particular the downregulation of fetuin-A in systemic inflammation. Decreased serum fetuin-A has been shown to be associated with a reduced capacity to inhibit calcium phosphate precipitation in vitro and is predictive of mortality in dialysis patients. These new insights into pathogenesis may lead to better prevention and treatment of calcification (e.g. with calcimimetics, anti-cytokines, etc.). However, the only preventive approach to have been established prospectively to date is the replacement of calcium-containing phosphate binders with sevelamer HCl, a non-calcaemic phosphate binder. Yet, it remains unclear whether sevelamer HCl reduces vascular calcification by preventing episodes of hypercalcaemia and/or by reducing low-density lipoprotein (LDL)-cholesterol levels.

Blood Proteins↗
PubMed2003

Mineral exploration: search for the mechanism of vascular calcification and beyond: the 2003 Jeffrey M. Hoeg Award lecture.

Research in the area of vascular calcification has grown rapidly in the past decade, and there is a greater understanding of its active regulatory mechanisms. This brief review covers the ideas presented in the 2003 Jeffrey M. Hoeg Award lecture, including the concepts that bone tissue forms in the artery wall in patients with atherosclerosis, that vascular cells undergo osteoblastic differentiation, that bone morphogenetic protein and matrix GLA protein regulate vascular calcification in opposition, that inflammatory cytokines and lipids promote vascular cell calcification but inhibit osteoblastic cell differentiation, that these same factors promote differentiation of bone-resorbing osteoclasts, and that the artery wall may contain osteoclast-like cells with the potential to resorb calcium mineral. The review closes with a mention of therapeutic possibilities and an evolutionary paradigm to explain the reciprocal responses of vascular and bone mineralization to inflammation.

Animals↗
PubMed2006

Hypercholesterolemia accelerates vascular calcification induced by excessive vitamin D via oxidative stress.

Hypercholesterolemia plays an important role in the initiation and progression of atherosclerosis and has a positive correlation with cardiovascular disease. Calcification is a common feature of atherosclerotic lesions and contributes to cardiovascular dysfunctions. The present study investigated the role of hypercholesterolemia in vascular calcification and its potential mechanism. Models of vascular calcification were established by administering vitamin D2 (VD) to rats alone or combined with a high-cholesterol diet (HCD) and by treating rat aorta smooth muscle cells (RASMCs) with beta-glycerophosphate (GP) alone or combined with oxidized low-density lipoprotein (oxLDL) in vitro. In rats, the combination of VD with HCD significantly enhanced vessel calcium deposition and the activity and mRNA expression of vessel alkaline phosphatase (ALP) compared to treatment with VD alone. This combination also enhanced serum levels of total cholesterol, oxLDL, and malondialdehyde as well as vascular production of superoxide anion, while it reduced the vascular activity of superoxide dismutase. Both simvastatin, a cholesterol-lowering agent, and antioxidant vitamin E antagonized the effects of the above combination. In RASMCs, oxLDL accumulation dependently accelerated calcium deposition in cell layers initiated by GP alone. Also, oxLDL stimulated ALP activity and mRNA expression in RASMCs in a concentration-dependent manner. Taken together, these results suggest that acceleration of vascular calcification by hypercholesterolemia might be attributed to oxidative stress and such calcification may be another target of statin or antioxidant action in antiatherosclerosis.

Animals↗
PubMed2006

Molecular determinants of vascular calcification: a bench to bedside view.

Vascular calcification (VC) is an orchestrated event, evoking the programmed process of the osteogenesis and triggered by inflammatory cytokines active at vascular level. VC is a dynamic process in which the vessel wall intima, media and also cardiac valves may be involved. Intimal calcification is an endochondral ossification process in which type II collagen is mineralized by calcium deposition. In contrast, an intra-membranous ossification process leads to medial calcification, while a dystrophic calcification process is responsible for valvular calcification. Mechanisms involved in VC may be summarized as: 1. Activation of osteogenesis in the vessel wall, 2. Loss of inhibitory factors, 3. Enhanced bone turnover, and 4. Abnormalities in mineral metabolism. The signaling axis constituted by osteoprotegerin (OPG), receptor activator nuclear factor kB (RANK) and its ligand (RANKL), along with the monocyte colony stimulating factor (M-CSF) and the transcription factor core Binding protein (Cbfa-1), play a pivotal role in the control of VC. In contrast, fetuin-A, matrix G1a protein (MGP) and osteopontin (OPN) control the inhibition of VC. In addition, abnormal mineral metabolism with enhanced phosphates availability favors calcium deposition. The inflammatory cytokines interleukin (IL-1) and tumor necrosis factor (TNF)-alpha enhance OPG and RANKL function in the vessel wall leading to VC. VC is a controlled process, depending on the balance between osteoblastic and osteoclastic influences and further modulated by the influence of risk factors like diabetes, smoking, age, hypertension and dyslipidemia. Recent advances in diagnostic tools such as with multi-detector computed tomography (MDCT) and electron beam computed tomography (EBCT), may help diagnosis and delineation of VC in the clinical setting and aid in understanding its prognostic value.

Animals↗
PubMedDate not supplied

Toward cell therapy for vascular calcification: osteoclast-mediated demineralization of calcified elastin.

BACKGROUND: Elastin-oriented vascular calcification is a clinically significant feature, which involves formation of ectopic bone-like structures. Taking advantage of the similarities between arterial calcification and bone regulation, our hypothesis was that therapeutic approaches for limitation of vascular calcification could be developed using site-specific delivery of autologous osteoclasts. In the present paper, we tested the hypothesis that bone-marrow-derived osteoclasts have the ability to demineralize calcified elastin, without significant alterations in elastin integrity. METHODS: Active, multinucleated osteoclasts were obtained by in vitro maturation of rat bone-marrow-derived progenitor cells in the presence of vitamin D(3) and retinoic acid. Cell phenotype was validated by staining for tartrate-resistant acid phosphatase, formation of resorption pits on hydroxyapatite-coated disks, and RT-PCR for identification of cathepsin K gene expression. Calcified aortic elastin was seeded with osteoclasts and calcium, and phosphorous levels were monitored in gels and culture media to detect demineralization of elastin. Soluble elastin peptides were also monitored in culture media for elastin degradation. For in vivo experiments, pure aortic elastin was coimplanted with allogenic osteoclasts subdermally into rats, and the degree of elastin calcification and degradation was evaluated using mineral analysis and desmosine quantitation. RESULTS: Bone-marrow-derived osteoclasts reduced mineral content of calcified elastin in vitro by 80%. Moreover, in vivo implantation of allogenic osteoclasts in the vicinity of calcifying elastin limited elastin mineralization by almost 50%, in the absence of detectable elastin degradation. CONCLUSIONS: Osteoclasts have the ability to demineralize calcified elastin, without significant alterations in elastin integrity.

Animals↗
PubMed2004

Vascular calcification: a stiff challenge for the nephrologist: does preventing bone disease cause arterial disease?

There has been an explosion of interest in vascular calcification in the last 5 years. Four key "germinal" findings have fallen onto very fertile soil. First, on the background of an increasing cardiovascular disease burden it has been found that at least cross-sectionally, and in a limited fashion prospectively, achieved dialysis plasma phosphate levels are linked to all-cause and cardiovascular mortality. Second, there are increasing reports of calcific uremic arteriolopathy in Australia and the United States. Third, we know know that the mechanical properties of the carotid artery, and the aorta, have a profound influence on survival for dialysis patients. Vascular calcification itself (as assessed by x-ray films and ultrasound) has been linked to aortic stiffness. Fourth, increasing numbers of studies are showing extremely extensive coronary artery calcification (CAC) in dialysis patients, even at a young age. From these apparently unlinked observations the following assertion has been posited-that in the widespread (over) use of calcium-containing oral phosphate binders (OPB) to prevent uremic osteodystrophy in our dialysis population we have unwittingly accelerated widespread uremic vasculopathy and thereby contributed to premature cardiovascular mortality. It is the purpose of this article to discuss vascular calcification (and particularly CAC) in dialysis patients as we understand it today. We will review the published series, with special reference to the Sevelamer Treat to Goal trial and also discuss the new Kidney Disease Outcome Quality Initiative (K-DOQI) guidelines on the use of phosphate binders in chronic kidney disease.

Bone Diseases↗
PubMed2004

Osteogenic regulation of vascular calcification: an early perspective.

Cardiovascular calcification is a common consequence of aging, diabetes, hypercholesterolemia, mechanically abnormal valve function, and chronic renal insufficiency. Although vascular calcification may appear to be a uniform response to vascular insult, it is a heterogenous disorder, with overlapping yet distinct mechanisms of initiation and progression. A minimum of four histoanatomic variants-atherosclerotic (fibrotic) calcification, cardiac valve calcification, medial artery calcification, and vascular calciphylaxis-arise in response to metabolic, mechanical, infectious, and inflammatory injuries. Common to the first three variants is a variable degree of vascular infiltration by T cells and macrophages. Once thought benign, the deleterious clinical consequences of calcific vasculopathy are now becoming clear; stroke, amputation, ischemic heart disease, and increased mortality are portended by the anatomy and extent of calcific vasculopathy. Along with dystrophic calcium deposition in dying cells and lipoprotein deposits, active endochondral and intramembranous (nonendochondral) ossification processes contribute to vascular calcium load. Thus vascular calcification is subject to regulation by osteotropic hormones and skeletal morphogens in addition to key inhibitors of passive tissue mineralization. In response to oxidized lipids, inflammation, and mechanical injury, the microvascular smooth muscle cell becomes activated. Orthotopically, proliferating stromal myofibroblasts provide osteoprogenitors for skeletal growth and fracture repair; however, in valves and arteries, vascular myofibroblasts contribute to cardiovascular ossification. Current data suggest that paracrine signals are provided by bone morphogenetic protein-2, Wnts, parathyroid hormone-related polypeptide, osteopontin, osteoprotegerin, and matrix Gla protein, all entrained to endocrine, metabolic, inflammatory, and mechanical cues. In end-stage renal disease, a "perfect storm" of vascular calcification often occurs, with hyperglycemia, hyperphosphatemia, hypercholesterolemia, hypertension, parathyroid hormone resistance, and iatrogenic calcitriol excess contributing to severe calcific vasculopathy. This brief review recounts emerging themes in the pathobiology of vascular calcification and highlights some fundamental deficiencies in our understanding of vascular endocrinology and metabolism that are immediately relevant to human health and health care.

Animals↗
PubMed2002

[Vascular calcification and bone-related factors].

Bone is consisted of bone matrix proteins produced by osteoblasts and minerals, Recently, it has been reported that bone-related factors are also involved in vascular calcification. Among bone matrix proteins, osteopontin and matrix Gla protein play important roles in vascular calcification. Regulatory factors for osteoblast differentiation (BMP) and osteoclast differentiation (osteoprotegerin) are also involved in vascular calcification.

English Abstract↗
PubMed1989

Cutaneous gangrene, vascular calcification, and hyperparathyroidism.

We describe the development of necrotic ulcers with underlying vascular calcification in a 72-year-old man who had chronic renal failure. These lesions had surrounding ecchymoses. The patient had a normal serum calcium concentration, an elevated parathyroid hormone level, and findings consistent with a parathyroid adenoma on ultrasonography. We consider this another case of a characteristic cutaneous syndrome secondary to underlying vascular calcification and hyperparathyroidism.

Aged↗
PubMed2004

Phosphate-induced vascular calcification: role of pyrophosphate and osteopontin.

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

Alkaline Phosphatase↗
PubMed2001

Role of vitamin K and vitamin K-dependent proteins in vascular calcification.

OBJECTIVES: To provide a rational basis for recommended daily allowances (RDA) of dietary phylloquinone (vitamin K1) and menaquinone (vitamin K2) intake that adequately supply extrahepatic (notably vascular) tissue requirements. BACKGROUND: Vitamin K has a key function in the synthesis of at least two proteins involved in calcium and bone metabolism, namely osteocalcin and matrix Gla-protein (MGP). MGP was shown to be a strong inhibitor of vascular calcification. Present RDA values for vitamin K are based on the hepatic phylloquinone requirement for coagulation factor synthesis. Accumulating data suggest that extrahepatic tissues such as bone and vessel wall require higher dietary intakes and have a preference for menaquinone rather than for phylloquinone. METHODS: Tissue-specific vitamin K consumption under controlled intake was determined in warfarin-treated rats using the vitamin K-quinone/epoxide ratio as a measure for vitamin K consumption. Immunohistochemical analysis of human vascular material was performed using a monoclonal antibody against MGP. The same antibody was used for quantification of MGP levels in serum. RESULTS: At least some extrahepatic tissues including the arterial vessel wall have a high preference for accumulating and using menaquinone rather than phylloquinone. Both intima and media sclerosis are associated with high tissue concentrations of MGP, with the most prominent accumulation at the interface between vascular tissue and calcified material. This was consistent with increased concentrations of circulating MGP in subjects with atherosclerosis and diabetes mellitus. CONCLUSIONS: This is the first report demonstrating the association between MGP and vascular calcification. The hypothesis is put forward that undercarboxylation of MGP is a risk factor for vascular calcification and that the present RDA values are too low to ensure full carboxylation of MGP.

Arteriosclerosis↗
PubMed2004

Bilateral extensive vascular calcification of the breast associated with coagulative necrosis: a calciphylaxis-like syndrome.

A case of asynchronous bilateral breast necrosis in a 40-year-old woman with untreated chronic hypercholesteraemia is described. Mastectomies were performed, and histological examination revealed bilateral breast calciphylaxis characterized by extensive vascular calcification with coagulative necrosis. Breast calciphylaxis is a rare disease clinically characterized by progressive tissular necrosis with secondary cutaneous ulceration and by vascular calcification and thrombosis. However, the nature of the vascular calcification has remained poorly understood up to now, owing to the absence of any precise mineralogical examination. In this case the mineral deposits were analysed for the first time: only hydroxyapatite was found. The etiology is discussed, and the high cholesterol rate of the patient is implicated.

Adult↗
PubMed2006

Accelerated vascular calcification and relative hypoparathyroidism in incident haemodialysis diabetic patients receiving calcium binders.

BACKGROUND: Vascular calcification and low bone turnover with a relatively low parathyroid hormone (PTH) often coexist in diabetic patients undergoing haemodialysis. Since calcium salts (CaS) are used extensively as primary phosphate binders and have been associated with progressive vascular calcification, we studied the effects of CaS on coronary arteries and parathyroid activity in incident haemodialysis diabetic patients. METHODS: We measured the change in coronary artery calcium scores (CACS) with sequential electron beam computed tomography (EBCT) in 64 diabetic and 45 non-diabetic patients, randomized to CaS or sevelamer within 90 days of starting haemodialysis. CACS measurements were repeated after 6, 12 and 18 months. Serum intact PTH (iPTH), calcium and phosphorus were serially tested. RESULTS: During the study period, serum phosphate was similar in diabetic and non-diabetic patients. Serum calcium levels were similar at baseline (2.3+/-0.25 mmol/l for both) and increased significantly with CaS treatment (P<0.05) both in diabetic and non-diabetic patients but not with sevelamer. Diabetic patients treated with CaS showed a significantly greater CACS progression than sevelamer-treated patients (median increase 177 vs 27; P=0.05). During follow-up, diabetic patients receiving CaS were significantly more likely to develop serum iPTH values<16 pmol/l than diabetic patients treated with sevelamer (33% vs 6%, P=0.005) and had a lower mean iPTH level (24+/-16 vs 31+/-14 pmol/l; P=0.038). CONCLUSIONS: The management of hyperphosphataemia with CaS in haemodialysis diabetic patients is associated with a significantly greater progression of CACS than with sevelamer. These effects are accompanied by iPTH changes suggestive of low bone turnover.

Acetates↗
PubMedDate not supplied

Vascular calcification, autonomic neuropathy, and peripheral blood flow in patients with diabetic nephropathy.

The possibility that digital gangrene in patients with diabetic nephropathy might be due to abnormalities of peripheral blood flow secondary to vascular calcification has been investigated. Twenty patients with renal failure due to diabetic nephropathy were studied. Peripheral blood flow was measured using venous occlusion plethysmography, together with an assessment of medial arterial calcification on plain radiographs of the hands and feet, and transcutaneous oxygen tension (TcPO2). Hallux blood flow was markedly raised (median 22.5, range 11.5-56.5, ml min-1 100-ml-1) compared with non-diabetic control subjects (4.7, 1.1-10.5, ml min-1 100-ml-1; p less than 0.01) and similar to that in diabetic patients with autonomic neuropathy (29.5, 16.7-49.6, ml min-1 100-ml-1). Although vascular calcification was common and extensive in the patients with diabetic nephropathy, TcPO2 measurements in the supine foot were normal and did not indicate tissue ischaemia. We conclude that despite extensive vascular calcification high peripheral blood flow occurs in the feet of these patients at rest together with normal transcutaneous oxygen tension.

Adult↗