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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies have shown that patients with high peritoneal transport characteristics have substantially increased morbidity and mortality. This finding is counter-intuitive, since HTs will a priori achieve higher clearances. There are many possible causes: increased protein losses with consequent hypoalbuminemia; poor ultrafiltration capacity causing fluid retention, ventricular hypertrophy and hypertension; increased glucose absorption leading to anorexia, hyperinsulinism, and local AGE formation; and the development of an atherogenic lipid profile. While common pathogenic causes of high peritoneal transport and atherosclerosis have been hypothesized, it is more likely that CAPD as currently practiced is unsuitable for HTs, who should be switched to HD or NIPD. Renal and peritoneal clearances have different clinical effects and should be assessed separately. Current measures of dialysis adequacy, such as total Kt/V, do not therefore describe the patient's clinical situation accurately and are insufficient.
Semin Dial
PMID:Pathogenic effects of a high peritoneal transport rate. 1083 80

It has been known for a long time that atherosclerosis, particularly plaques in the epicardiac coronary conduit arteries, are more frequent in patients with chronic renal failure than in non-uraemic patients. It has been only recently, however, that modification of post-stenotic remodelling of cardiac arteries as well as abnormalities of the arterioles and the capillaries in the myocardium of uraemic animals and uraemic patients have been recognized and analysed. These lesions can be dissociated from changes in blood pressure and may be an important cause contributing to reduced ischaemia tolerance and cardiac malfunction (pump failure, arrhythmia) thus predisposing to cardiac death. Recent insights into angiogenesis, particularly adaptive angiogenesis in response to hypoxia, may potentially provide novel approaches to the understanding and management of cardiac microangiopathy in renal failure.
Nephrol Dial Transplant 2000 Oct
PMID:Microvascular disease--the Cinderella of uraemic heart disease. 1100 10

Endothelial nitric oxide synthase (eNOS) serves a number of functions in the vasculature. In response to stimuli such as shear stress or acetylcholine, eNOS catalyses the production of nitric oxide (NO) from L-arginine. The NO diffuses across the endothelium into neighbouring smooth muscle and induces vasodilation. NO also acts locally to prevent platelet and leucocyte aggregation and inhibits vascular smooth muscle cell proliferation. It has been shown that mice lacking eNOS have decreased blood pressure, decreased heart rate and increased plasma renin activity. It has also been reported that NO production was reduced in patients with essential hypertension compared with normotensive individuals. In several animal models of renal disease (subtotal renal ablation, ureteral obstruction and diabetes), the administration of L-arginine, and probably the increase in NO synthesis, reduced the degree of glomerulosclerosis, ameliorated the changes in the tubulointerstitial compartment of the kidney and also decreased the infiltration of the kidney by invading macrophages. In summary, the L-arginine-NO pathway plays an important role in hypertension, renal disease, inflammation and atherosclerosis. This pathway also interacts with the renin-angiotensin system, the eicosanoid pathway, endothelin, cytokines and regulators of inflammation such as NF-kappaB.
Nephrol Dial Transplant 2001
PMID:The role of nitric oxide in hypertension and renal disease progression. 1136 23

Anaemia is a frequent complication of many diseases but the mechanisms that link reduced blood oxygen content to the long-term consequences of anaemia are incompletely understood. The maintenance of oxygen supply to the tissues during anaemia involves complex cardiovascular adaptations, including an increase in cardiac output, reduced peripheral resistance and increased oxygen extraction from haemoglobin (Hb). In addition, hypoxia-inducible factors are associated with the transcriptional activation of genes involved in adaptive mechanisms that increase oxygen delivery and provide alternative metabolic pathways. The complex pathophysiology of chronic kidney disease alters the adaptations to anaemia in uraemic patients. The increased cardiac output induced by anaemia is associated with left ventricular hypertrophy and cardiac disease in renal patients. Alterations in endothelial cell function, common in renal disease, may diminish endothelium-induced vasodilatation, increase the risk of atherosclerosis and impair angiogenesis. Many potential reasons for erythropoietin-induced hypertension in uraemic patients have been postulated, including increased blood viscosity as haematocrit rises, a reversal of hypoxic vasodilatation, increased blood volume that is not compensated by haemodialysis, ultrafiltration and impaired nitric oxide synthesis, preventing vascular relaxation in response to increased blood viscosity. In view of this impaired vascular reactivity, rapid increases in haematocrit should be avoided during epoetin treatment. As the interaction between anaemia and uraemia is very complex, it is not possible to derive the optimal Hb concentration for individual patients by using simple physiological or pathophysiological models and there is a need for good randomized controlled clinical trials to address this issue.
Nephrol Dial Transplant 2001
PMID:Anaemia in end-stage renal disease: pathophysiological considerations. 1159 Feb 49

Chronic inflammation is a common feature of end-stage renal disease (ESRD) that is gaining increasing attention as a major cause of morbidity and mortality. It is well established that ESRD per se carries a heightened risk of inflammatory disorders and other co-morbid conditions, but it should also be pointed out that dialysis treatment per se can bring additional risk factors for inflammation, such as impure dialysate or bio-incompatible membranes. Inflammation has recently been associated with atherosclerosis and malnutrition in ESRD, and this link has led to the development of the malnutrition, inflammation, atherosclerosis (MIA) hypothesis. This describes a syndrome whereby raised levels of pro-inflammatory cytokines (such as IL-1, IL-6 and TNF-alpha) are a common link between malnutrition, inflammation and atherosclerosis. Also, anaemia appears to be an important element linking elevated cytokine levels with poor patient outcomes. Several mechanisms for cytokine-induced anaemia have been proposed, including intestinal bleeding, impaired iron metabolism and suppression of bone marrow erythropoiesis and erythropoietin production. These effects suggest that pro-inflammatory cytokines may also be an important cause of lack of response to recombinant human erythropoietin (rh-Epo) therapy. In the light of this putative role of pro-inflammatory cytokines, anti-cytokine agents may prove useful to optimize efficacy of rh-Epo in anaemic chronic renal failure patients. Other potential therapeutic strategies include minimizing exposure to causes of inflammation from various co-morbid conditions, such as persistent infections and chronic heart failure.
Nephrol Dial Transplant 2001
PMID:The role of inflammation in the anaemia of end-stage renal disease. 1159 Feb 55

Cardiovascular disease is the leading cause of morbidity and mortality in dialysis patients and current research indicates that it might be linked to high serum phosphorus levels and calcium-phosphorus product. The severe osteopathy known to exist in end-stage renal disease (ESRD) patients is often coupled with an inability of bone to handle excess calcium loads. This might predispose to overflow and deposition of calcium and phosphate crystals in various soft tissues and in particular the cardiovascular apparatus. Atherosclerosis is a slow process that expands in the context of the arterial intimal layer and it is for the most part associated with extracellular calcification. Electron beam tomography (EBT) is a radiological technique utilized to non-invasively visualize this silent marker of atherosclerosis: vascular calcification. Several investigations conducted in non-ESRD patients have conclusively demonstrated that coronary calcification indicates a high risk for cardiac events. As EBT allows precise estimates of the extent of vascular and valvular calcification, it might become an important clinical tool in ESRD patients to assess the effect of excess calcium and phosphate load in soft tissues, estimate the cardiovascular risk of events and gauge the effectiveness of therapy.
Nephrol Dial Transplant 2002 Feb
PMID:Effects of excess calcium load on the cardiovascular system measured with electron beam tomography in end-stage renal disease. 1181 1

Cardiovascular disease (CVD) is the most common cause of death in adults with end-stage renal disease and after renal transplantation, and the relative excess of mortality is greatest in the young. The most likely explanation is the dramatic accumulation of both classical and uremic risk factors leading to atherosclerosis, uremic vasculopathy, and uremic cardiomyopathy. Prospective studies have established the significance of classical and uremic risk factors for the occurrence of CVD in the normal population and in the population with chronic renal disease alike. However, whether and to what degree modification of risk factors by therapeutic intervention can lower morbidity and mortality rates is as yet unknown.
Perit Dial Int 2001
PMID:Undertreatment of cardiac risk factors in adolescents with renal failure. 1188 37

End-stage renal disease (ESRD) is characterized by a high mortality rate, derived largely from cardiovascular disease (CVD). In patients with ESRD, high levels of pro-inflammatory cytokines and increased oxidative stress are common features that may contribute to malnutrition, anaemia, recombinant human erythropoietin (rHuEPO) resistance, and atherosclerosis. Inflammation predicts poor outcome in ESRD. It is multifactorial in cause and, while it may reflect the underlying CVD, the acute-phase response may also contribute to both oxidative stress and progressive vascular injury. In patients with ESRD, the acute-phase response may be influenced by a number of factors unrelated to dialysis and perhaps by the dialysis procedure itself. Inflammation and the acute-phase response interact with the haematopoietic system at several levels resulting in reduced erythropoiesis, accelerated destruction of erythrocytes, and blunting of the reactive increase in erythropoietin in response to reduced haemoglobin levels. In patients with ESRD, rHuEPO resistance has been linked with inflammation, the latter of which is often associated with a state of functional iron deficiency. Patients with ESRD are thought to have a reduced capacity to handle oxidative stress. There is recent evidence that a relationship may exist between inflammation and oxidative stress and treatment of anaemia with rHuEPO. However, iron may also generate oxidative stress. Controlled trials are needed before evidence-based recommendations for the management of inflammation-induced anaemia and resistance to rHuEPO can be defined.
Nephrol Dial Transplant 2002
PMID:Anaemia, rHuEPO resistance, and cardiovascular disease in end-stage renal failure; links to inflammation and oxidative stress. 1209 5

Immunosuppressive treatment is a critical procedure in dialysis patients, in whom an increased risk of infection is already present. Haemodialytic treatment increases the patient's susceptibility to bacterial infection, mainly by impairing polymorphonuclear leukocyte phagocytosis, but it can also restore the patient's immunological defences by improving the T-cell function, which is reduced by pre-dialysis uraemia. Patients on dialysis usually continue the immunosuppressive treatment that had been established for the illness that caused their renal failure [e.g. systemic lupus erythematosus (SLE) or renal vasculitis]. Less frequently, patients on dialysis need immunosuppression for immunological or inflammatory diseases that appear 'de novo' after initiation of dialysis. SLE and antineutrophil cytoplasmic antibody (ANCA)-related vasculitides are immunological illnesses that frequently cause end-stage renal failure (ESRF). A reduction in serological and/or clinical activity is usually observed in SLE patients after they reach ESRF, but a similar or increased frequency of extrarenal relapse episodes in lupus patients after the beginning of the dialysis, compared with the pre-dialysis period, has also been described. Frequency of relapse episodes in patients on dialysis treatment for ANCA-related vasculitides varies from 10 to 30% per patient/year in different reports, and it is higher than the frequency of relapses after renal transplantation; anti-rejection therapy seems to be the most likely protective factor in these conditions. The treatment of relapse episodes in SLE or ANCA vasculitis in dialysis-dependent patients is usually not different from treatment of relapses in patients with dialysis-independent renal function. However, the risk of severe infection caused by immunosuppressive treatment is relevantly higher in dialysis patients. Furthermore, there is a lack of prospective controlled studies indicating the optimal management of immunosuppressive protocols in dialysis patients. A particularly careful assessment of the patient's risks and benefits is necessary in deciding how long immunosuppressive treatment should last after acute or rapidly progressive renal damage, that should require dialysis treatment, in patients with SLE or ANCA vasculitis. In the above conditions, the risks of prolonging immunosuppressive treatment must be balanced against the relatively good prognosis offered to these patients by dialysis and renal transplantation. In a retrospective review of 24 patients receiving long-term steroid therapy (>3 months) in our dialysis unit in the past 5 years, we found relevant clinical differences in the patients receiving steroid treatment compared with 24 controls. Steroid-treated patients showed less favourable nutritional conditions, with lower serum albumin and body mass index vs non-steroid-treated patients; moreover, C-reactive protein values were persistently higher in the steroid-treated group. Steroid treatment in these patients was usually performed at the beginning of regular dialysis, as a continuation of the treatment that started before the initiation of dialysis. Only two patients, who needed a prolonged low-dose steroidal treatment to control a malnutrition-inflammation-atherosclerosis (MIA) syndrome, started steroids many years after beginning dialysis. Steroid treatment was effective in improving the nutritional condition and inflammatory symptoms in these two patients after all conventional measures had failed.
Nephrol Dial Transplant 2002
PMID:Immunosuppressive treatment in dialysis patients. 1214 70

Cardiovascular pathology is the major cause of death in uraemia. There is evidence that a chronic inflammation with activation of C-reactive protein, interleukin-6, tumour necrosis factor-alpha and other cytokines is associated with vascular pathology, both in the general population and in dialysis patients. The cardiovascular system, and particularly the vascular wall, is the main target of the inflammatory process. Inflammation of the coronary arteries could be involved in the development of atherosclerosis and its related clinical syndromes. In the uraemic state, an increased production of pro-inflammatory cytokines may trigger the onset and progression of atherosclerosis and favour the subsequent complications, such as plaque fissuration and rupture. However, inflammatory cytokines also have a depressant action on the myocardium, thus inducing myocardial dysfunction. Together, these conditions may ultimately enhance the risk of myocardial infarction and death. From this standpoint, cardiovascular disease should also be investigated with the traditional biochemical inflammation markers and the evaluation of the circulating cytokine level, although new reliable markers could provide further diagnostic help. New therapeutic approaches should also be considered.
Nephrol Dial Transplant 2002
PMID:Cardiac effects of chronic inflammation in dialysis patients. 1214 71


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