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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The risk of cardiovascular disease is significantly higher in patients with long-term uremia than in otherwise healthy adults. In addition, the risk is greater than what would be predicted from classic vascular risk factors. This is true even before patients proceed to dialysis. Although the reasons for this accelerated vascular disease are unknown, transendothelial transport of lipids and other macromolecules in both large vessels and the microcirculation has been implicated in the generation of cardiovascular disease. Furthermore, endothelial cell dysfunction is widely accepted as a cardinal feature of both modest and dialysis-dependent uremia, and is regarded as a critical step in the initiation of this aggressive pathology. This overview considers the severity of the clinical problem, the nature of the vascular endothelium, microvascular permeability (and the measurement thereof) as a functional property of the endothelium, and the in vitro and in vivo evidence for endothelial dysfunction in uremia.
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PMID:Endothelial permeability in uremia. 1269 6

The uraemic syndrome is a complex condition that results from the retention of "waste" compounds that normally would be excreted into the urine or catabolized by the kidneys. In addition, inflammation has been implicated in symptoms associated with uraemia, including its role in the malnutrition-inflammation-atherosclerosis syndrome. Regarding vascular disease, traditional risk factors such as hypertension and gender do not seem to have the same significance in the uraemic population compared with patients without renal failure, and so the possibility has been raised that the uraemic toxins that result in the uraemic syndrome could play a role in this process. In this review, various questions are addressed regarding the involvement of cytokines in uraemia and the effects of dialysis membranes and fluids in patients receiving haemodialysis or peritoneal dialysis on cytokine levels. The effects of non-dialysis-related factors on levels of cytokines, mortality rates and other uraemic disorders are also discussed. It is concluded that cytokines are undoubtedly retained in uraemia, and that the loss of renal excretion almost certainly plays a key role in this process. Many cytokines have a pro-inflammatory role, probably resulting in a number of clinical events that are related to the increased morbidity and mortality of uraemic and haemodialysis patients. Any adjustment of the subtle balance between pro- and anti-inflammation by medical interventions should be conducted carefully because of an enhanced risk of serious infectious episodes. Bioincompatibility of dialysis techniques probably enhances the generation of cytokines as well as other uraemic toxins.
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PMID:Interleukin/cytokine profiles in haemodialysis and in continuous peritoneal dialysis. 1528 59

Patients with chronic kidney disease (CKD) have a substantially increased risk of cardiovascular disease (CVD) compared with the general population. The high prevalence of established traditional risk factors for atherosclerosis (diabetes, hypertension, dyslipidemia) in these patients undoubtedly contributes to the accelerated rate of vascular disease. In addition, several hypotheses have emerged to explain the high prevalence of CVD in patients with chronic renal failure. Growing evidence has been gathered over the last 15 years regarding the role of uremia-related risk factors such as inflammation and oxidant stress in the pathogenesis of atherosclerosis in subjects with renal failure. This paper will review current knowledge regarding the potential role of these non-traditional or uremia-related risk factors for atherosclerosis with special emphasis on prevalence, cardiac risk, and management in patients with CKD.
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PMID:[Vascular risk factors and renal failure]. 1558 63

Glycation adducts formed in the later stages of protein glycation reactions, advanced glycation endproducts (AGEs), are a class of uraemic toxin. Protein glycation was viewed originally as a post-translational modification that accumulated mostly on extracellular proteins. We now know that AGE residues are also formed on short-lived cellular and extracellular proteins. Cellular proteolysis forms AGE free adducts from these proteins, which are released into plasma for urinary excretion. AGE free adducts are also absorbed from food. AGE free adducts are the major molecular form by which AGEs are excreted in urine. They normally have high renal clearance, but this declines markedly in chronic renal failure patients, leading to profound increases in plasma AGE free adducts. Accumulation of plasma AGE free adducts is increased further in end stage renal disease patients on peritoneal dialysis and haemodialysis by increased AGE formation. The impact of AGEs absorbed from food is probably most marked for undialysed patients with mild uraemia. The toxicity of AGEs has been associated with resistance of the extracellular matrix to proteolysis and AGE receptor-mediated responses. AGE free adducts may also contribute to vascular disease in uraemia. They represent an important new age for glycation research in nephrology.
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PMID:Glycation free adduct accumulation in renal disease: the new AGE. 1613 53

Small uncontrolled studies of dialysis-dependent CKD (chronic kidney disease) patients have demonstrated abnormalities of cardiovascular autonomic control and vascular compliance, which may contribute to adverse cardiovascular morbidity in this population. However, there is little information utilizing newer non-invasive techniques in pre-dialysis patients with increasing degrees of uraemia. In the present study, 55 non-dialysis-dependent non-diabetic CKD patients with mean GFR (glomerular filtration rate) of 27 ml x min(-1) x m(-2) were studied. All patients underwent a 10-min period of electrocardiographic and non-invasive blood pressure monitoring. Cardiac BRS (baroreceptor sensitivity) was calculated from the combined alpha-index. PWV (pulse wave velocity) measurement and determination of arterial wave reflexion by applanation tonometry was performed in all patients. Mean (S.D.) cardiac BRS was 10.8 (7.1) ms/mmHg and mean (S.D.) PWV was 8.6 (1.7) m/s. Reduced GFR was correlated with increased PWV and decreased cardiac BRS. On logistic regression analysis with adjustment for clinical significant risk factors, severely impaired renal function (assessed by GFR < 15 ml x min(-1) x m(-2)) was associated with increased large artery stiffness [odds ratio for PWV = 3.14 (95% confidence intervals, 1.03-9.53); P = 0.04] and increased cardiovascular autonomic dysfunction [odds ratio for BRS = 0.87 (95% confidence intervals, 0.75-1.80); P = 0.06]. In conclusion, non-dialysis dependent non-diabetic CKD patients with decreasing GFR have reduced cardiac BRS and increased large artery stiffness. This may have important prognostic and therapeutic consequences for the management of vascular disease in a pre-dialysis population.
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PMID:Reduced glomerular filtration rate in pre-dialysis non-diabetic chronic kidney disease patients is associated with impaired baroreceptor sensitivity and reduced vascular compliance. 1617 54

It is being increasingly recognized that cardiovascular disease (CVD) and its complications are the most important cause of morbidity and mortality in patients with chronic kidney disease (CKD) and dialysis patients. If outcomes for these patients are to be improved, therapeutic strategies at all stages of CKD will have to target the etiologies and mechanisms that lead to CVD. In this review, we focus on the central role of endothelial dysfunction as the critical precursor of CVD. We argue that a better understanding of endothelial dysfunction by nephrologists and dialysis physicians is necessary if there is to be success in limiting the CVD epidemic that kills and maims our patients. The extensive studies to explain the high prevalence of vascular disease in patients with CKD have shown the close relationship among endothelial dysfunction, inflammation, and atherosclerosis. The pathogenesis starts with endothelial cell injury from any of many possible causes, and strategies to reduce the burden of CVD in uremic and dialysis patients must be directed at restoring normal endothelial function or, at the least, preventing aggravation of endothelial damage. At the center of the exploration of endothelial dysfunction and atherosclerosis are oxidative stress and inflammation. Of these, which is the chicken and which is the egg is unknown, but in the setting of uremia, endothelial injury because of free radical, oxidative stress is likely to precede inflammation. The issues raised here are highly complex and most renal practitioners may not have been adequately exposed to the background research underlying current thinking of the pathogenesis of vascular disease. Clearly, progress in management of CVD in patients with CKD will require collaboration with experts in the research and treatment of vascular disease. Nephrologists seeking optimum outcomes for patients with CKD will need to become "endotheliologists" or, at the least, subscribe to a mission "to protect the endothelium."
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PMID:Protecting the endothelium: a new focus for management of chronic kidney disease. 1644 26

Vascular calcification increasingly afflicts our aging and dysmetabolic population. Once considered a passive process, it has emerged as an actively regulated form of calcified tissue metabolism, resembling the mineralization of endochondral and membranous bone. Executive cell types familiar to bone biologists, osteoblasts, chondrocytes, and osteoclasts, are seen in calcifying macrovascular specimens. Lipidaceous matrix vesicles, with biochemical and ultrastructural "signatures" of skeletal matrix vesicles, nucleate vascular mineralization in diabetes, dyslipidemia, and uremia. Skeletal morphogens (bone morphogenetic protein-2 (BMP) and BMP4 and Wnts) divert aortic mesoangioblasts, mural pericytes (calcifying vascular cells), or valve myofibroblasts to osteogenic fates. Paracrine signals provided by these molecules mimic the epithelial-mesenchymal interactions that induce skeletal development. Vascular expression of pro-osteogenic morphogens is entrained to physiological stimuli that promote calcification. Inflammation, shear, oxidative stress, hyperphosphatemia, and elastinolysis provide stimuli that: (1) promote vascular BMP2/4 signaling and matrix remodeling; and (2) compromise vascular defenses that limit calcium deposition, inhibit osteo/chondrogenic trans-differentiation, and enhance matrix vesicle clearance. In this review, we discuss the biology of vascular calcification. We highlight how aortic fibrofatty tissue expansion (adventitia, valve interstitium), the adventitial-medial vasa, vascular matrix, and matrix vesicle metabolism contribute to the regulation of aortic calcium deposition, with greatest emphasis placed on diabetic vascular disease.
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PMID:Molecular mechanisms of vascular calcification: lessons learned from the aorta. 1660 Dec 33

Until the early nineteenth century, diabetes mellitus was regarded as a disease of the kidney, in which there was an increase in the volume of urine and a wasting of the flesh. With the identification of glucose in blood and urine in the late eighteenth century, first it was re-framed as a disease of assimilation and only then became a metabolic disorder. Whilst these changing concepts were debated, it was noted in parallel that diabetics might show coagulable urine containing albumin, even before Bright and others had established this as a sign of kidney disease. Wilhelm Griesinger (1817-1868) was perhaps the first to suggest in 1859 that the diabetes might be causing the Bright's disease, with the latter as a 'complication'. During the next half-century the observation that as albuminuria appeared and increased, so glycosuria improved or might remit, with a parallel or subsequent evolution into uraemia. Glomerulosclerosis and arteriolosclerosis were described in occasional patients during the same period, but text-books of pathology ignored these observations. Thus it was only when diabetics began to survive longer using insulin treatment in the early 1920s that a diabetic nephropathy became widely recognized. After a few isolated descriptions which were ignored, the now famous paper of Paul Kimmelstiel and Clifford Wilson appeared in 1935 detailing nodular renal lesions in just 8 maturity-onset (48-68 year old) diabetics. They barely noted the association with diabetes however, and it was Arthur Allen in 1941 who clarified the association in 105 patients with diabetes, again all aged over 40. Despite the age of the patients in these early studies, diabetic nephropathy became thought of as a disease of young diabetics as a cohort of survivors of juvenile diabetes passed 15 years or more of disease and more than half developed nephropathy. In the 1950s the technique of renal biopsy was rapidly applied to the study of diabetics, and the early lesions defined using electron microscopy as well as optical methods. Then the role of diabetic nephropathy as a cause of renal failure changed: to begin with numbers of young insulin-requiring diabetics were small and infrequently referred for dialysis treatment or transplantation. Then in the 1970s and 1980s the proportion of such juvenile-onset diabetics developing renal failure gradually fell, but at the same time much larger numbers of older diabetics survived their vascular disease and required treatment for renal failure. World-wide, today diabetes accounts for 20-50% of patients entering established renal failure programs, and absolute numbers increase as greater longevity and western-style living has promoted an 'epidemic' of diabetes at all ages.
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PMID:The discovery of diabetic nephropathy: from small print to centre stage. 1687 18

We report a case of a 23-year-old man with adult onset Still's disease (AOSD) developing a rare, life-threatening complication of thrombotic microangiopathy (TMA). While the AOSD was in an active phase, our patient first developed hemolytic uremia syndrome, soon followed by convulsions, sudden loss of vision, and thrombotic angiopathy of retinal vessels. After immediate and aggressive treatment with high dose prednisolone and 18 courses of plasmapheresis, he recovered from this severe complication. We think that the occurrence of TMA in AOSD may not be coincidental, although more reports are needed to support this. Early recognition and aggressive immunotherapy can allow patients with AOSD to completely recover from this life-threatening complication.
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PMID:Thrombotic microangiopathy in a patient with adult onset Still's disease. 1704 86

Chronic oxidative stress that characterizes uremia has potentially devastating effects on the vasculature and has been advocated in the pathogenesis of accelerated atherosclerosis in this disease. Recent advances have been made in our understanding of the molecular mechanisms that regulate expression and activity of key enzymes of vascular oxidative stress (eg, nicotinamide adenine dinucleotide phosphate [NAD{P}H] oxidase) and that dissect their interactions with signalling pathways of inflammation. The finding that NAD(P)H oxidase is upregulated in experimental uremia has important consequences from a physiologic and a therapeutic standpoint. In addition, identification of novel proteins involved in systemic oxidative stress has shed some new light on the pathogenesis of vascular disease. p66(shc) is a cytoplasmic protein that is expressed in a wide range of cell types. Initially believed to be involved in signalling pathways that regulate cell growth and oxidative stress, it has now been shown to play a pivotal role in promoting endothelial dysfunction and atherosclerosis. Although a specific role in uremia-related vascular disease has not yet been shown, available data in humans suggest involvement of p66(shc) in clinical conditions associated with increased oxidative stress.
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PMID:Vascular sources of oxidative stress: implications for uremia-related cardiovascular disease. 1719 33


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