Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007222 (cardiovascular disease)
 65,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Abnormalities of bone mineral parameters (calcium, phosphate, vitamin D, and parathyroid hormone) are nearly always present in patients with chronic kidney disease (CKD). These typically consist of hypocalcemia, hyperphosphatemia, abnormalities of vitamin D metabolism, and secondary hyperparathyroidism, and are now defined as CKD mineral bone disorders (CKD-MBD). Currently, emerging evidence indicates that deficiencies in vitamin D receptor (VDR) activation play crucial roles in adversely affecting the cardiovascular health of CKD patients. VDRs are not restricted to skeletal tissue, but are instead widely expressed throughout the body at several sites, such as in cardiac tissue, vascular smooth muscle cells, endothelial cells, renal tissue, and cells of the immune system. Restoring the physiology and modulation of VDR activator levels results in correlative regulatory effects on mineral homeostasis, hypertension, cardiovascular disease, and vascular calcification, as well as a number of other endpoints in cardiac and renal pathology. Among the compounds available for treatment of CKD-MBD, paricalcitol is a selective VDR activator. The term 'selective' refers to paricalcitol being more selective in affecting VDR pathways in the parathyroid gland compared with bone and intestine. As such, paricalcitol's selectivity allows for a wider therapeutic window with effects beyond parathyroid hormone control and mineral management, and may explain, in part, the increased survival advantage with paricalcitol treatment.
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PMID:Restoring the physiology of vitamin D receptor activation and the concept of selectivity. 2162 4

Higher serum phosphate levels within the normal range are associated with substantially increased risk of cardiovascular disease events. Whether this reflects a causative relationship is unknown. Phosphate-responsive hormones (fibroblast growth factor-23, parathyroid hormone and calcitriol) are also predictors of cardiovascular mortality in populations without kidney disease or recognised disturbances of bone mineral metabolism. The high bioavailable phosphate content of Western diets may contribute to this apparent discrepancy between 'normal' and optimal phosphate axis parameters. Although uremic hyperphosphatemia is recognised to cause vascular medial calcification, this does not readily explain the association of higher-normal phosphate with common athero-occlusive phenomena. The phosphate axis may in fact play a role in atherogenesis; observational data link higher levels of phosphate and fibroblast growth factor-23 with coronary atheroma burden, whilst dietary phosphate supplementation accelerates atherosclerosis in a mouse model. In vitro studies show adverse effects of phosphate increases on both vascular smooth muscle cells and endothelium, though these observations have not yet been extended to phosphate increments within the normal range. Receptors for phosphate-responsive hormones are present throughout the cardiovascular system and may mediate atherogenic effects. Since interventions are already available to manipulate the phosphate axis, this is an important issue. If an atherogenic role for phosphate exposure is demonstrated then phosphate binders could become the new statins.
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PMID:Phosphate: the new cholesterol? The role of the phosphate axis in non-uremic vascular disease. 2196 38

Hyperphosphatemia is a major risk factor for cardiovascular disease, abnormalities of mineral metabolism and bone disease, and the progression of renal insufficiency in patients with chronic renal disease. In early renal disease, serum phosphate levels are maintained within the 'normal laboratory range' by compensatory increases in phosphaturic hormones such as fibroblast growth factor-23 (FGF-23). An important co-factor for FGF-23 is Klotho; a deficiency in Klotho plays an important role in the pathogenesis of hyperphosphatemia, renal tubulointerstitial disease, and parathyroid and bone abnormalities. Clinical hyperphosphatemia occurs when these phosphaturic mechanisms cannot counterbalance nephron loss. Hyperphosphatemia is associated with calcific uremic arteriolopathy and uremic cardiomyopathy, which may explain, in part, the epidemiologic connections between phosphate excess and cardiovascular disease. However, no clinical trials have been conducted to establish a causal relationship, and large, randomized trials with hard endpoints are urgently needed to prove or disprove the benefits and risks of therapy. In summary, hyperphosphatemia accelerates renal tubulointerstitial disease, renal osteodystrophy, as well as cardiovascular disease, and it is an important mortality risk factor in patients with chronic kidney disease.
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PMID:Phosphate Metabolism in Cardiorenal Metabolic Disease. 2209 58

Secondary and tertiary hyperparathyroidism (HPT) develop in patients with renal failure due to a variety of mechanisms including increased phosphorus and fibroblast growth factor 23 (FGF23), and decreased calcium and 1,25-dihydroxy vitamin D levels. Patients present with various bone disorders, cardiovascular disease, and typical laboratory abnormalities. Medical treatment consists of controlling hyperphosphatemia, vitamin D/analog and calcium administration, and calcimimetic agents. Improved medical therapies have led to a decrease in the use of parathyroidectomy (PTX). The surgical indications include parathyroid hormone (PTH) levels >800 pg/ml associated with hypercalcemia and/or hyperphosphatemia despite medical therapy. Other indications include calciphylaxis, fractures, bone pain or pruritis. Transplant recipients often show decreased PTH, calcium and phosphorus levels, but some will have persistent HPT. Evidence suggests that PTX may cause deterioration in renal graft function in the short-term calling into the question the indications for PTX in these patients. Pre-operative imaging is only occasionally helpful except in re-operative PTX. Operative approaches include subtotal PTX, total PTX with or without autotransplantation, and possible thymectomy. Each approach has its proponents, advantages and disadvantages which are discussed. Intraoperative PTH monitoring has a high positive predictive value of cure but a poor negative predictive value and therefore is of limited utility. Hypocalcemia is the most common complication requiring aggressive calcium administration. Benefits of surgery may include improved survival, bone mineral density and alleviation of symptoms.
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PMID:The surgical management of renal hyperparathyroidism. 2210 74

The course and treatment of chronic kidney disease (CKD) is adversely affected by numerous metabolic disarrangements, comorbid states and general diseases, i.e. hyperphosphatemia and metabolic bone disease, chronic inflammation, accelerated atherosclerosis (partly of infectious etiology) and devastating cardiovascular disease. Furthermore, CKD patients are usually afflicted by multiple oral abnormalities, including troublesome oral dryness and the very aggressive form of periodontal disease. The use of chitosan-containing chewing gum in CKD subjects seems to offer a novel therapeutic approach of interdisciplinary importance: the chitosan binds salivary phosphates and, when swallowed, likely phosphates in the alimentary tract, thus beneficially lowering blood phosphate levels, while the gum itself increases impaired salivary flow and has a potent oral antimicrobial activity. Thus, it effectively improves general oral hygiene and prevents progression of periodontal disease being (besides of hyperphosphatemia) one of the established causes of atherosclerosis development/progression. The undemanding maneuver of chewing the chitosan-containing, phosphate-binding gum has a potential to diminish excessive morbidity in CKD patients.
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PMID:[Salivary phosphate-binding chewing gum--an integrative approach to chronic kidney disease and oral diseases]. 2233 15

Osteoporosis is a common complication of chronic kidney disease (CKD), and the latter is a major risk factor for cardiovascular mortality. Recent studies have elucidated some of the mechanisms by which CKD is a cardiovascular risk, and they relate to osteoporosis. Thus, the mechanisms of CKD induced cardiovascular risk provide valuable insight into the relationship between cardiovascular disease and osteoporosis, and they are reviewed here. Observational studies have determined hyperphosphatemia to be a cardiovascular risk factor in chronic kidney disease. Mechanistic studies have elucidated that hyperphosphatemia is a direct stimulus to vascular calcification, which is one cause of morbid cardiovascular events contributing to the excess mortality of chronic kidney disease. Hyperphosphatemia in chronic kidney is due to failure of excretion by the kidneys and excess bone resorption. It stimulates vascular cells to mineralize atherosclerotic plaques through osteoblastic processes. Hyperphosphatemia in chronic kidney disease is a distinct syndrome characterized by disordered skeletal remodeling, heterotopic mineralization and cardiovascular morbidity. The heterotopic mineralization stimulated by CKD is relevant to osteoporosis.
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PMID:Osteoporosis and cardiovascular disease: lessons from chronic kidney disease. 2246 Aug 43

Awareness of phosphorus intake is important because both phosphorus deficiency and overloading impair bone health and quality of life. Phosphorus consumption is increasing in many countries. Most dietary phosphorus is contained in protein-rich foods such as meat, milk, cheese, poultry, fish, and processed foods that contain phosphate-based additives to improve their consistency and appearance. Elevation of extracellular phosphorus levels causes endothelial dysfunction and medial calcification, which are closely associated with the development of cardiovascular disease (CVD). Long-term excessive phosphorus loading, even if it does not cause hyperphosphatemia, can be a risk factor for CVD. In epidemiological studies, higher levels of phosphorus intake have been associated with reduced blood pressure. Interestingly, when examined further, phosphorus from dairy products, but not from other sources, was usually associated with lower blood pressure. A dietary approach to phosphorus reduction is particularly important to prevent bone impairment and CVD in patients with chronic kidney disease. In order to improve bone health and quality of life in the general population, the impact of phosphorous, including in processed foods, should be considered, and measures to indicate the amount of phosphorous in food products should be implemented.
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PMID:Dietary phosphorus in bone health and quality of life. 2264 25

Hyperphosphatemia causes endothelial dysfunction as well as vascular calcification. Management of serum phosphate level by dietary phosphate restriction or phosphate binders is considered to be beneficial to prevent chronic kidney disease patients from cardiovascular disease, but it has been unclear whether keeping lower serum phosphate level can ameliorate endothelial dysfunction. In this study we investigated whether low-phosphate diet can ameliorate endothelial dysfunction in adenine-induced kidney disease rats, one of useful animal model of chronic kidney disease. Administration of 0.75% adenine-containing diet for 21 days induced renal failure with hyperphosphatemia, and impaired acetylcholine-dependent vasodilation of thoracic aortic ring in rats. Then adenine-induced kidney disease rats were treated with either control diet (1% phosphate) or low-phosphate diet (0.2% phosphate) for 16 days. Low-phosphate diet ameliorated not only hyperphosphatemia but also the impaired vasodilation of aorta. In addition, the activatory phosphorylation of endothelial nitric oxide synthase at serine 1177 and Akt at serine 473 in the aorta were inhibited by in adenine-induced kidney disease rats. The inhibited phosphorylations were improved by the low-phosphate diet treatment. Thus, dietary phosphate restriction can improve aortic endothelial dysfunction in chronic kidney disease with hyperphosphatemia by increase in the activatory phosphorylations of endothelial nitric oxide synthase and Akt.
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PMID:Dietary phosphate restriction ameliorates endothelial dysfunction in adenine-induced kidney disease rats. 2279 9

Vitamin D and its metabolites have wide-spread physiological roles far beyond the well described effects in skeletal biology. Many physiological processes are directly or indirectly regulated by vitamin D and in consequence, vitamin D deficiency is implicated in numerous disease conditions. Summarizing previous assumptions on the optimal vitamin D levels in humans these data point towards calcidiol levels of approximately 30 ng/ml as being sufficient. The role of vitamin D deficiency in cardiovascular disease is a relatively novel field of interest. Well substantiated experimental data describe convincingly regulatory effects of vitamin D regarding various cardiovascular risk factors such as hypertension and diabetes mellitus. Activation of the vitamin D receptor suppresses e.g. the renin-angiotensin system. These experimental data are strongly supported by epidemiological and observational human data that link vitamin D deficiency to the incidence, degree and prevalence of cardiovascular risk factors and disease conditions. In contrast to the in vivo data and to the homogenous non-interventional observations, we know much less about controlled prospectively evaluated supplementation of vitamin D as a potentially therapeutic agent on cardiovascular events. High quality, large, and randomized controlled trials aiming primarily on cardiovascular end-points are absent. Speculations about the vitamin D usage in prevention or therapy of cardiovascular disease need to take potential drawbacks of vitamin D overdosing into account: Vitamin D overdosing might induce hypercalcemia, hyperphosphatemia, and increases in fibroblast growth-factor 23. The limited evidence regarding vitamin D therapy currently prevents general recommendations for vitamin D application in cardiology.
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PMID:The role of vitamin D in cardiovascular disease: from present evidence to future perspectives. 2292 24

Hyperphosphatemia is the most common complication among patients with chronic kidney disease. Large scale observational studies have identified hyperphosphatemia as an independent risk factor for cardiovascular disease and mortality in hemodialysis patients. The combination therapy of dietary phosphate restriction and phosphate removal with dialysis treatment is still not enough to achieve the serum phosphate within the target. Thererfore, phosphate binders is necessary for many dialyzed patients with hyperphosphatemia. In this article, we will review the detail and development of phosphate binders and recommendation for clinical practice in hyperphosphatemia.
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PMID:[Newly development of phosphate binders in hyperphosphatemic patients with kidney dysfunction]. 2302 37


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