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)

Management of secondary hyperparathyroidism (SHPT) in chronic kidney disease patients on hemodialysis (HD) can be challenging. Conventional treatments can lead to hypercalcemia and hyperphosphatemia, both of which are associated with vascular and soft tissue calcification and increased risk of cardiovascular disease. We report the effect of treatment with the Type II calcimimetic cinacalcet on vascular calcification in a HD patient with SHPT. A 40-year-old male with a 24-year history of kidney failure secondary to mesangial proliferative glomerulonephritis, commenced HD in October 2004 following chronic graft dysfunction. The patient was admitted to hospital with renal insufficiency and metabolic abnormalities. An anatomopathological study showed calcium (Ca) deposits in the alveolar septa, bronchial wall and pulmonary arterioles. Parathyroid methoxy isobutyl isonitrile (MIBI) scintigraphy revealed multiglandular parathyroid disease and an ectopic gland behind the sternal notch. Serum intact parathyroid hormone (iPTH) was repeatedly found to be > or = 2,500 pg/ml, and was accompanied by significant abnormalities in phosphorus (P) and Ca metabolism which were difficult to control. The patient was initially treated with sevelamer, low dose calcium carbonate, a low P and reduced protein diet and high doses of intravenous erythropoietin. In addition, he received HD with a high efficiency membrane for 4.5 hours, 4-times weekly. Treatment with cinacalcet was initiated at 30 mg/day and adjusted to achieve National Kidney Foundation Kidney Disease Outcomes Quality Initiative targets for iPTH, P, Ca and Ca-P product. One year following cinacalcet treatment, a chest x-ray showed a moderate reduction in Ca deposits, a bone X-ray showed a significant reduction in vascular calcifications, and parathyroid MIBI scintigraphy showed a disappearance of ectopic focus and minimal remains of glands. Significant reductions in calcemia were controlled by concomitant modifications to oral Ca supplementation, Ca concentration in the dialysis liquid, and administration of paricalcitriol. In the second year of treatment, iPTH was maintained within the target range, with moderate rises in P and stabilization of serum Ca. An echocardiogram showed an improvement in left ventricular hypertrophy. Chest and hand X-rays showed a progressive reduction in calcifications. Radiology showed an improvement in bone morphology, with reduced trabeculation and better cortical definition in the phalanx bones. In conclusion, the changes in iPTH, P and Ca associated with cinacalcet treatment were accompanied by reduced vascular and soft tissue calcification in this patient. There were no cardiovascular events and the patient experienced a marked improvement in quality of life.
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PMID:Cinacalcet reduces vascular and soft tissue calcification in secondary hyperparathyroidism (SHPT) in hemodialysis patients. 1920 18

Cardiovascular disease is a frequent complication of renal failure and is the most common cause of death in patients with chronic kidney disease (CKD). Accelerated atherogenesis has been widely documented in CKD and diabetic nephropathy is the leading cause of renal failure worldwide. Furthermore, CKD promotes hypertension and dyslipidemia, which in turn may contribute to the progression of renal failure. All together, hypertension, dyslipidemia and diabetes are considered major risk factors for the development of endothelial dysfunction and progression of atherosclerosis. Elevated inflammatory mediators and activation of the renin-angiotensin system contribute through enhanced production of reactive oxygen species, to atherogenesis in CKD. Vascular calcification is also important. Calcification of arteries occurs in the intima in association with atherosclerosis, where it may contribute to plaque formation, and in the media, where it causes stiffening. Increased serum levels of calcification promoters, such as hyperphosphatemia, and a decrease in circulating and local inhibitors of calcification, favor vascular calcification. On the other hand, transdifferentiation of vascular smooth muscle cells to osteblast-like cells would be the pivotal event in calcification. Bone morphogenetic protein agonists and antagonists are playing a role in this osteogenic differentiation. Accelerated atherosclerosis and media calcification will then lead to increased prevalence of coronary artery disease, heart failure, stroke, and peripheral arterial disease. Prevention and treatment of cardiovascular disease are major considerations in the management of individuals with CKD.
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PMID:[Vascular damage in chronic kidney disease]. 1930 81

Vascular calcification is associated with the mortality of patients with chronic kidney disease (CKD) . Susceptibility to vascular calcification is genetically determined and actively regulated by diverse inducers and inhibitors. One of these inducers, hyperphosphatemia, promotes vascular calcification and is a nontraditional risk factor for CVD mortality in CKD patients. Hyperphosphatemia promotes vascular calcification in part by promoting VSMCs to undergo an osteochondrogenic phenotype change through a mechanism requiring sodium-dependent phosphate cotransporters. Recent randomized clinical trials showed that lowering serum phosphate levels with a non-calcium containing phosphate binder slows progression of vascular calcification in ESRD patients. Moreover, calcimimetics reduce arterial remodeling and calcification in rats with subtotal nephrectomy. Whether this difference will also be found in humans and will ultimately translate into less CV events in calcimimetics treated uremic patients is for a matter for speculation. Calcium and phosphate load are an important driver of vascular calcification.
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PMID:[Chronic kidney disease (CKD) and bone. Vascular calcification in CKD]. 1932 35

Decline in renal function is related directly to cardiovascular mortality. However, traditional risk factors do not fully account for the high mortality in these patients. Activated vitamin D, a hormone produced by the proximal convoluted tubule of the kidney, appears to have beneficial effects beyond suppressing parathyroid hormone (PTH). However, activated vitamin D also can cause hypercalcemia and hyperphosphatemia in chronic kidney disease. Newer agents such as vitamin D receptor activators (eg, paricalcitol) suppress PTH with reduced risk of hypercalcemia and hyperphosphatemia. Recent evidence from animal and preliminary human studies supports an association between vitamin D receptor activators and reduced risk of cardiovascular disease deaths, irrespective of PTH levels. New pathways of vitamin D regulation also have been discovered, involving fibroblast growth factor-23 and klotho. Although considerable work has been performed to advance our understanding of the effects of vitamin D in health and chronic kidney disease, more investigations and randomized trials need to be performed to elucidate the mechanistic underpinnings of these effects.
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PMID:Role of vitamin D in chronic kidney disease. 1937 2

In recent years the interest in understanding the clinical significance and the pathogenic mechanisms involved in vascular calcification has rapidly increased. There are three reasons that explain this increasing interest in vascular calcification by nephrologists: a) cardiovascular disease is the leading cause of death in uremic patients; b) hyperphosphatemia is a predictor of death and bone mineral disorders are not only responsible for renal osteodystrophy but are also involved in the pathophysiology of vascular calcification, and c) vascular calcification in large arteries reduces vascular compliance inducing serious hemodynamic consequence. The aim of this review is to analyze the clinical aspects, summarize the mechanisms involved in vascular calcification, as well as, the strategies to prevent or at least to slow down progression of vascular calcification.
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PMID:[Vascular calcification and arteriosclerosis in chronic kidney disease patients]. 1946 Apr 80

Higher levels of serum phosphate are associated not only with progression of secondary hyperparathyroidism but also adverse cardiovascular outcomes, such as ectopic calcifications, cardiovascular events its death. The treatments of hyperphosphatemia with phosphate binders were shown to be effective on a risk factor for cardiovascular disease and mortality on hemodialysis patients.
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PMID:[Clinical aspect of recent progress in phosphate metabolism. Phosphate retension, a powerful risk factor for mortality in chronic kidney disease (CKD)]. 1948 78

The most frequent cause of death in hemodialysis patients is cardiovascular disease with chronic inflammation being an epidemiologically proved risk factor. Many studies have shown C-reactive protein (CRP) as the strongest predictor of long-term mortality of hemodialysis patients, while other reports have indicated acute phase proteins as potential predictors of the mortality. The present study therefore aimed to evaluate the prevalence of chronic inflammation in hemodialysis patients and the role of acute phase proteins together with lipids and divalent ions for predicting mortality in hemodialysis patients. Chronic inflammation was defined, based on the serum level of high sensitive CRP > 8.4 mg/L and/or serum amyloid-A (SAA) > 8.9 mg/L. Acute phase proteins are defined as one whose plasma concentration increase (positive) or decreases (negative) by at least 25% during inflammation. High sensitive CRP and SAA were positive acute phase proteins measured, while albumin and fetuin-A, a calcification inhibitor, were selected as negative acute phase proteins. This prospective 36-month follow-up study included 130 patients (60 males and 70 females, aged 55.1 +/- 12.9 years) maintained by hemodialysis for 107.2 +/- 54.72 months at a Nephrology Clinic in Belgrade. The prevalence of chronic inflammation was 35.4% (46 patients). During the follow-up period, 24 patients (18.5%) died and 2 patients received transplants. In multivariate analysis, potential independent predictors of mortality in hemodialysis patients are hyperphosphatemia, hypoalbuminemia, and high SAA. Considering that assays for SAA are widely used, we propose that SAA is the best predictor for outcomes of end-stage renal disease.
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PMID:Serum amyloid-A rather than C-reactive protein is a better predictor of mortality in hemodialysis patients. 1977 29

Most patients with chronic kidney disease experience abnormalities in serum calcium, phosphorus, parathyroid hormone, and vitamin D metabolism. These can lead to vascular calcification (VC), which has been associated with increased risk for cardiovascular disease and mortality. Although hyperphosphatemia is believed to be a risk factor for mortality and VC, no randomized trial was ever designed to demonstrate that lowering phosphate reduces mortality. Nonetheless, binders have been used extensively, and the preponderance of evidence shows that sevelamer slows the development of VC whereas calcium salts do not. Four studies have demonstrated a slower progression of VC with sevelamer than with calcium-containing binders, although a fifth study showed nonsuperiority. Conversely, the results on mortality with sevelamer have been variable, and data on calcium-based binders are nonexistent. Improved survival with sevelamer was demonstrated in a small randomized clinical trial, whereas a larger randomized trial failed to show a benefit. In addition, preclinical models of renal failure and preliminary clinical data on hemodialysis patients suggest a potential benefit for bone with sevelamer. Meanwhile, several randomized and observational studies suggested no improvement in bone density and fracture rate, and a few noted an increase in total and cardiovascular mortality in the general population given calcium supplements. Although additional studies are needed, there are at least indications that sevelamer may improve vascular and bone health and, perhaps, mortality in hemodialysis patients, whereas data on calcium-based binders are lacking.
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PMID:Ten-year experience with sevelamer and calcium salts as phosphate binders. 2008 1

The death rate from cardiovascular disease for dialysis patients is much higher than the general population, regardless of age. Observational data indicate that there is a close inter-relationship between progressive renal dysfunction in patients with chronic kidney disease cardiovascular disease and mortality. Continuously evidence indicates that deficiencies in vitamin D receptor activation represents one of key players in adversely affecting cardiovascular health, as well as inducing to secondary hyperparathyroidism in chromic kidney disease patients. Vitamin D receptors are widely expressed throughout the body and modulations of vitamin D levels results in correlative regulatory effects on mineral metabolism homeostasis, cardiovascular disease, and vascular calcification. The management of SHPT has developed enormously in recent years and different drug classes are available to treat this disease. Potentially, selective VDR activators not only reduce serum parathyroid hormone levels minimizing the risk of hypercalcemia and hyperphosphatemia, but also may improve patient health, reducing the risk of cardiovascular disease.
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PMID:The role of vitamin D receptor activation in chronic kidney disease. 2041 Oct 52

Cardiovascular disease is the leading cause of death among patients with stage 5 chronic kidney disease. Several mechanisms are thought to contribute to vascular calcification and subsequent cardiovascular disease in patients who require hemodialysis. One of these mechanisms is the use of calcium-containing phosphate binders to treat hyperphosphatemia. Although most phosphate binding occurs in the gastrointestinal tract, some calcium is inevitably absorbed and has the potential to perpetuate the calcium-phosphorus product and the development of vascular and soft tissue calcification. Some phosphate binders such as sevelamer hydrochloride do not contain calcium and therefore may not carry the same risks. We examined the cardiovascular calcification effect and morbidity and mortality data with calcium-containing phosphate binders compared with sevelamer hydrochloride when given to patients with stage 5 chronic kidney disease for the treatment of hyperphosphatemia. A literature search using the MEDLINE and PubMed databases identified relevant articles from 1989-2009; nine studies compared vascular calcification between a calcium-containing phosphate binder and sevelamer hydrochloride. Three mortality studies were also identified. Seven of the nine studies reported a statistically significant increase in vascular calcification in patients taking calcium-containing phosphate binders as measured by coronary artery calcification scores and aortic calcification scores. In two trials, lower mortality rates were observed in the patients receiving sevelamer hydrochloride compared with calcium-containing phosphate binders. No significant difference in the mortality rate was observed in the third trial. Based on the current literature, it appears that calcium-containing phosphate binders promote the progression of vascular calcification to a greater extent than does sevelamer hydrochloride. In addition, some evidence suggests that sevelamer hydrochloride may reduce all-cause mortality rates in patients undergoing hemodialysis, particularly those aged 65 years or older. Thus, although sevelamer hydrochloride appears to be the more appropriate choice of phosphate binder for patients undergoing hemodialysis in whom cardiovascular calcification is a concern, more clinical trials are needed to further guide practitioners on the selection of phosphate binders.
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PMID:Evaluation of morbidity and mortality data related to cardiovascular calcification from calcium-containing phosphate binder use in patients undergoing hemodialysis. 2057 37


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