Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypoalbuminemia is the result of the combined effects of inflammation and inadequate protein and caloric intake in patients with chronic disease such as chronic renal failure. Inflammation and malnutrition both reduce albumin concentration by decreasing its rate of synthesis, while inflammation alone is associated with a greater fractional catabolic rate (FCR) and, when extreme, increased transfer of albumin out of the vascular compartment. A vicious cascade of events ensues in which inflammation induces anorexia and reduces the effective use of dietary protein and energy intake and augments catabolism of the key somatic protein, albumin. Hypoalbuminemia is a powerful predictor of mortality in patients with chronic renal failure, and the major cause of death in this population is due to cardiovascular events. Inflammation is associated with vascular disease and likely causes injury to the vascular endothelium, and hypoalbuminemia as two separate expressions of the inflammatory process. Albumin has a myriad of important physiologic effects that are essential for normal health. However, simply administering albumin to critically ill patients with hypoalbuminemia has not been shown to improve survival or reduce morbidity. Thus the inference from these clinical studies suggests that the cause of hypoalbuminemia, rather than low albumin levels specifically, is responsible for morbidity and mortality.
Semin Dial
PMID:Serum albumin: relationship to inflammation and nutrition. 1566 May 73

Although traditional risk factors for cardiovascular disease are common in dialysis patients, they alone cannot explain the unacceptably high prevalence of vascular disease in this patient group. Much recent interest has therefore focused on the role of various nontraditional cardiovascular risk factors, such as inflammation, wasting, obesity, vascular calcification, and oxidative stress. In addition, genetic factors such as single nucleotide polymorphisms (SNPs) may significantly influence the immune response, the levels of inflammatory markers and body composition, as well as the prevalence of vascular calcification in this patient group. While genetic variations in the tumor necrosis factor (TNF)-alpha-308 and interleukin (IL)-10 -1082 SNPs seem to be consistently associated with adverse clinical outcome in end-stage renal disease (ESRD) patients, the results regarding genetic variations in the IL-6 gene have been conflicting. To elucidate the respective role of DNA polymorphisms in the IL-6 and C-reactive protein (CRP) genes, as well as genes that encode vascular calcification inhibitors (such as fetuin-A, matrix Gla protein, and osteoprotegerin), sufficiently powered studies are needed in which both the protein product and the specific phenotype are determined. In addition, polymorphisms in genes related to body composition may be excellent candidates for analysis in the ESRD population, since nutritional parameters are strongly associated with adverse events in these patients. It seems conceivable that in the future, prognostic or predictive multigene DNA assays (which allow a simultaneous and rapid assessment of multiple genetic variants) will provide nephrologists with a more precise approach for the identification of "high-risk" ESRD patients and the development of accurate individualized treatment strategies.
Semin Dial
PMID:Gene polymorphism association studies in dialysis: the nutrition-inflammation axis. 1607 56

In the present study, we used high sensitivity C-reactive protein (hs-CRP) analysis in combination with lipid screening [which has been reported to be a more valuable risk marker than other novel markers such as homocysteine (Hcy) and lipoprotein a] to perform cardiovascular risk assessment in peritoneal dialysis (PD) and hemodialysis (HD) patients. We selected 9 PD patients, 10 HD patients, and 9 control subjects for the study. In those patients, we determined levels of serum lipids, hs-CRP, Hcy, vitamin B12, folic acid, and leptin. Patients on PD had a significantly elevated hs-CRP concentration (3.14 +/- 0.79 mg/L) and ratio of total cholesterol (TC) to high density lipoprotein (HDL) cholesterol (4.71 +/- 0.40), and their cardiovascular risk was found to be three times that of control subjects. In HD patients, the elevation of hs-CRP was more profound (5.66 +/- 1.30), but their TC:HDL ratio fell within the normal range (3.18 +/- 0.13). However, a cardiovascular risk assessment of the HD group showed the same risk as in the PD group. Serum Hcy was also elevated in patients on PD (54.95 +/- 18.08 microl/L) and on HD (25.33 +/- 3.70 micromol/L) as compared with healthy subjects (13.76 +/- 0.94 micromol/L). Folic acid and vitamin B12 levels (needed to remethylate Hcy to methionine) were not compromised in the dialysis population. On the other hand, leptin secreted by adipose tissue was found to be mildly higher in PD patients (37.08 +/- 12.59 ng/mL). The mean leptin level in control subjects was 14.14 +/- 3.60 ng/mL. The proinflammatory and proangiogenic action of excess leptin may aggravate cardiovascular risk in PD patients. Increased values of known risk factors were found in dialysis patients on PD and on HD. However, lower levels of HDL cholesterol, higher cardiovascular risk assessment and Hcy levels, and mildly increased leptin levels seem to increase the potential threat of vascular disease in PD patients more than in HD patients.
Adv Perit Dial 2005
PMID:Cardiovascular risk assessment and homocysteine and leptin levels in peritoneal dialysis and hemodialysis patients. 1668 91

Higher cholesterol is strongly associated with an increased risk of coronary heart disease (CHD) in nonrenal populations, so the lack of a clear positive association between total cholesterol and mortality among dialysis patients is unexpected. This review of prospective studies of the association between total cholesterol and mortality among dialysis patients suggests that there is a negative association at below average cholesterol levels and a flat or weakly positive association at higher levels. In nonrenal populations total cholesterol is not positively associated with vascular causes of death other than CHD, so the lack of a strongly positive association at above average cholesterol concentrations in dialysis patients may be explained by the high proportion of deaths due to non-CHD vascular causes. The observation of a negative association between total cholesterol and mortality at below average cholesterol concentrations in some studies is consistent with confounding by both vascular and nonvascular morbidity (i.e., reverse causality). We argue that evaluating the importance of cholesterol for vascular disease risk in dialysis patients can only be achieved through the eradication of confounding by randomization, and that ongoing trials of cholesterol-lowering therapy will provide a definitive answer to this question.
Semin Dial
PMID:Misleading associations between cholesterol and vascular outcomes in dialysis patients: the need for randomized trials. 1799 Nov 94

Homocysteine has been implicated in atherosclerotic and thrombotic vascular disease in the general and in the end-stage renal disease (ESRD) population as well. Although not strong, the risk associated with raised homocysteine (25% risk excess for a 5 mum increase) is quite consistent across studies in the general population. Likewise, individuals harboring a polymorphism leading to higher homocysteine levels coherently display an increased risk for cardiovascular events in comparison with individuals without such a polymorphism. Randomized controlled trials of homocysteine-lowering therapy performed so far failed to prove causality but the size effect of these interventions is still compatible with the hypothesis that reducing the plasma levels of this aminoacid may be beneficial. In ESRD, high homocysteine is a coherent predictor of death and adverse cardiovascular events in patients without malnutrition and inflammation. In the sole randomized placebo-controlled study performed in this population folic acid produced a small beneficial effect which, because of the lack of power, failed to achieve statistical significance. In another randomized study testing the effect of a well established homocysteine-lowering agent, N-acetyl-cysteine, a 40% reduction in cardiovascular events was observed. There is still insufficient knowledge to draw definitive conclusions on the causal implication of homocysteine in the high risk of ESRD. The contention that the homocysteine pathway cannot be used for interventions aimed at curbing cardiovascular risk in this population is, at least by now, unwarranted.
Semin Dial
PMID:It is important to lower homocysteine in dialysis patients. 1799 Nov 99

Chronic kidney disease (CKD) is a growing public health problem. The incidence of kidney failure is rising in all age groups but particularly in older adults. Individuals in all stages of CKD are at higher risk for development of cognitive impairment and this may be a major determinant in their quality of life. Furthermore, cognitive impairment is associated with an increased risk of death in dialysis patients. Cerebrovascular disease is a strong risk factor for development of cognitive impairment and vascular disease is a more likely cause of cognitive impairment than Alzheimer's disease in patients with CKD. Both traditional and nontraditional vascular risk factors are more common in CKD and dialysis patients may also be at risk for cognitive impairment via nonvascular risk factors and the hemodialysis procedure itself. Unfortunately, because risk factors for cognitive impairment in CKD have not been thoroughly ascertained, evaluation of potential treatments has been limited. Given the high prevalence of cognitive impairment in all stages of CKD, additional studies are needed to evaluate potential risk factors and treatments in this vulnerable population.
Semin Dial
PMID:Cognitive function in chronic kidney disease. 1825 55

Tunneled dialysis catheters are simultaneously a benefit and burden for hemodialysis patients. The infectious and vascular complications of catheters are well documented. Despite this, prevalence of catheter use in the US hemodialysis population remains high and could be due in part to increased efforts to create arteriovenous (AV) fistulas in most new end-stage renal disease patients. The editorial argues that creating fistulas instead of prosthetic grafts is the correct approach and that inadequately diagnosed and treated primary fistula failure is a major cause of excessive and prolonged catheter dependency. An understanding of AV fistula physiology and the treatable causes of primary fistula failure are key to maximizing the percentage of created fistulas that are successfully used for dialysis. Diagnosis of fistula malfunction based on history, physical examination, and hemodynamic and angiographic evaluation is discussed, and treatment strategies presented. A major emphasis is placed on early primary fistula failure recognition and intervention. It is the author's contention if adequate vein and artery are selected for initial fistula construction nearly all fistulas should eventually function adequately to support dialysis and sooner than previously appreciated by utilizing an array of percutaneous and surgical therapies. Fistula malfunction is a unique problem within the spectrum of vascular disease and therefore demands that patients are treated by physicians with demonstrated expertise and experience.
Semin Dial
PMID:A challenge for nephrologists--increasing fistula maturation rates, reducing fistula maturation time, and decreasing dialysis catheter prevalence in the United States. 1853 69

Sevelamer is an ion-exchanging resin that binds phosphate in the gut. Because it does so without increasing the calcium load, treatment with sevelamer may lead to less vascular calcification and better survival in chronic kidney disease patients. However, the results of available clinical studies have not been consistent; recent observations challenge the hypothesis that the extra calcium load inherent in calcium-based phosphate binder therapy increases cardiovascular mortality by accelerating vascular calcification. This reemphasizes the fact that we still lack detailed understanding on the complex relationships between vascular calcification, bone metabolism, vascular disease and outcome in the context of uremia. Thus, the role of phosphate binders may be more complex than initially anticipated and not limited to the extra calcium load. Even if detailed mechanisms of action for sevelamer are not yet clearly established (except for its lipid-lowering action), sevelamer may have a number of additional nonphosphate-lowering actions (including lipid lowering as well as improvement in endothelial function, modulation of inflammation and oxidative stress and binding of uremic toxin absorption). Whether these potentially very interesting pleiotropic effects of sevelamer may be translated into significant clinical benefits remains to be established.
Semin Dial
PMID:Nonphosphate-binding effects of sevelamer--are they of clinical relevance? 1857 37

The objective of this study was to evaluate the correlation of bone mineral density (BMD), evaluated by DXA, with vascular calcifications, arterial stiffness, and vascular disease in patients on peritoneal dialysis. Vascular calcifications were evaluated by vascular calcification score on plain x ray, and arterial stiffness was measured by pulse wave velocity using the Complior device (Artech Medical, Pantin, France). Adjusting for multiple factors, lower BMD at the femoral neck, but not at the lumbar spine, was associated with higher pulse wave velocity (p = 0.037), higher vascular calcification score (p = 0.013), and peripheral artery disease (p = 0.006). These data reinforce the hypothesis of the existence of a link between bone disease and cardiovascular disease in dialysis patients.
Perit Dial Int
PMID:Bone mineral density, vascular calcifications, and arterial stiffness in peritoneal dialysis patients. 1898

Magnesium (Mg) is the fourth most abundant cation in the body, mainly located within bone and skeletal muscle. The normal total plasma Mg concentration varies in a narrow range, with approximately 60% present as free Mg ions, the biologically active form. The kidney plays a principal role in Mg balance. Approximately 70-80% of plasma Mg is ultrafilterable, and under normal circumstances, 95% of the filtered load of Mg is reabsorbed. As chronic renal failure (CRF) progresses, urinary Mg excretion may be insufficient to balance intestinal Mg absorption and dietary Mg intake becomes a major determinant of serum and total body Mg levels. Until severe reductions in glomerular filtration rate (<30 ml/min), serum Mg levels are usually normal; with lower rates of renal function, serum Mg is increased. Concerning dialysis patients, dialysate Mg plays a critical role in maintaining Mg homeostasis, with serum Mg being largely dependent on the concentration of the ion in the dialysis solution. Magnesium has been implicated in diverse consequences, both beneficial and deleterious, in patients with CRF and dialysis. Potential harmful effects of elevated Mg include altered nerve conduction velocity, increased pruritus, and alterations to osseous metabolism and parathyroid gland function (mineralization defects, contribution to osteomalacic renal osteodystrophy, and adynamic bone disease). Hypermagnesemia also may retard vascular calcification. Low Mg levels have been associated with impairment of myocardial contractility, intradialytic hemodynamic instability, and hypotension. In addition, low Mg has been also linked to carotid intima-media thickness, a marker of atherosclerotic vascular disease and a predictor of vascular events.
Semin Dial
PMID:Clinical implications of disordered magnesium homeostasis in chronic renal failure and dialysis. 1925 Apr 45


<< Previous 1 2 3 4 5 6 Next >>