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)

Activated vitamin D continues to be the major treatment for suppressing parathyroid hormone (PTH) levels in dialysis patients who have secondary hyperparathyroidism. Active vitamin D compounds are distinguished by their ability to bind with high affinity to vitamin D receptors (VDRs) not only in the parathyroid glands, but in cells throughout the body. Because of recent data showing that pulsatile, intravenous vitamin D treatment (calcitriol or paricalcitol) confers a survival advantage in the dialysis population, there is new interest in understanding the systemic effects of VDR activation, particularly in the predialysis stages of chronic kidney disease (CKD), where high mortality rates from cardiovascular disease have recently been documented. Previous underutilization of calcitriol treatment to control PTH levels in stages 3 and 4 CKD was often due to concerns about its potential for accelerating the progression of CKD as a consequence of hypercalcemia, hypercalciuria, or hyperphosphatemia. Vitamin D analogs with selective VDR activity (such as paricalcitol) have great potential for preventing parathyroid hyperplasia and bone loss in early CKD without adversely affecting kidney function. Whether they also reduce cardiovascular morbidity and mortality in early CKD, as they appear to do in dialysis patients, remains to be determined.
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PMID:Vitamin D treatment in chronic kidney disease. 1607 55

Childhood renal osteodystrophy (ROD) is the consequence of disturbances of the calcium-regulating hormones vitamin D and parathyroid hormone (PTH) as well as of the somatotroph hormone axis associated with local modulation of bone and growth cartilage function. The resulting growth retardation and the potentially rapid onset of ROD in children are different from ROD in adults. The biochemical changes of ROD as well as its prevention and treatment affect calcium and phosphorus homeostasis and are directly associated with the development of cardiovascular disease in pediatric renal patients. The aims of the clinical and biochemical surveillance of pediatric patients with CRF or on dialysis are prevention of hyperphosphatemia, avoidance of hypercalcemia and keeping the calcium phosphorus product below 5 mmol(2)/l(2). The PTH levels should be within the normal range in chronic renal failure (CRF) and up to 2-3 times the upper limit of normal levels in dialysed children. Prevention of ROD is expected to result in improved growth and less vascular calcification.
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PMID:Prevention and treatment of renal osteodystrophy in children on chronic renal failure: European guidelines. 1624 44

Vascular calcification is often encountered in advanced atherosclerotic lesions and is a common consequence of aging. Calcification of the coronary arteries has been positively correlated with coronary atherosclerotic plaque burden, increased risk of myocardial infarction, and plaque instability. Chronic kidney disease (CKD) patients have two to five times more coronary artery calcification than healthy age-matched individuals. Vascular calcification is a strong prognostic marker of cardiovascular disease mortality in CKD patients. Vascular calcification has long been considered to be a passive, degenerative, and end-stage process of atherosclerosis and inflammation. However, recent evidence indicates that bone matrix proteins such as osteopontin, matrix Gla protein (MGP), and osteocalcin are expressed in calcified atherosclerotic lesions, and that calcium-regulating hormones such as vitamin D3 and parathyroid hormone-related protein regulate vascular calcification in in vitro vascular calcification models based on cultured aortic smooth muscle cells. These findings suggest that vascular calcification is an actively regulated process similar to osteogenesis, and that bone-associated proteins may be involved in the development of vascular calcification. The pathogenesis of vascular calcification in CKD is not well understood and is almost multifactorial. In CKD patients, several studies have found associations of both traditional risk factors, such as hypertension, hyperlipidemia, and diabetes, and uremic-specific risk factors with vascular calcification. Most patients with progressive CKD develop hyperphosphatemia. An elevated phosphate level is an important risk factor for the development of calcification and cardiovascular mortality in CKD patients. Thus, it is hypothesized that an important regulator of vascular calcification is the level of inorganic phosphate. In order to test this hypothesis, we characterized the response of human smooth muscle cell (HSMC) cultures to inorganic phosphate levels. Our findings indicate that inorganic phosphate directly regulates HSMC calcification through a sodium-dependent phosphate transporter mechanism. After treatment with elevated phosphate, there is a loss of smooth muscle lineage markers, such as alpha-actin and SM-22alpha, and a simultaneous gain of osteogenic markers such as cbfa-1 and osteocalcin. Elevated phosphate may directly stimulate HSMC to undergo phenotypic changes that predispose to calcification, and offer a novel explanation of the phenomenon of vascular calcification under hyperphosphatemic conditions. Furthermore, putative calcification inhibitory molecules have been identified using mouse mutational analyses, including MGP, beta-glucosidase, fetuin-A, and osteoprotegerin. Mutant mice deficient in these molecules present with enhanced cardiovascular calcification, demonstrating that specific molecules are normally important in suppressing vascular calcification. These findings suggest that the balance of inducers, such as phosphate, and inhibitors, such as MGP, fetuin-A, and others, are likely to control whether or not calcification occurs under pathological conditions.
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PMID:Vascular calcification in chronic kidney disease. 1650 29

Cardiovascular disease (CVD) remains the major mortality risk in dialysis patients, accounting for almost 50 percent of deaths. Risk is related to the increased prevalence of traditional risk factors for CVD and to the contribution of abnormalities in mineral metabolism as well as cardiovascular calcification. Hyperphosphatemia invariably is present among patients with end-stage renal disease and is becoming an increasingly important clinical entity. In addition to its role in the pathogenesis of secondary hyperparathyroidism, elevated serum phosphorus increases the mortality risk among these patients. The pathophysiologic mechanisms by which persistent hyperphosphatemia enhances mortality risk in dialysis patients are not yet completely understood. Given that inadequate control of serum phosphorus contributes to elevated calcium-phosphorus (Ca x P) product, hyperphosphatemia may play a key role in cardiovascular calcification. The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (K/DOQI) "Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease" recommends more stringent levels for controlling serum phosphorus and Ca x P product to improve patients' quality of life and longevity. Several studies, including the CARE study, have shown that calcium acetate is more cost-effective than sevelamer as a phosphate binder. Although concern has been raised about its purported link to cardiovascular calcification, the author demonstrates in this review that calcium acetate can be used effectively with doses of elemental calcium that meet the K/DOQI guidelines.
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PMID:The CARE study and cardiovascular calcification. 1660 43

In the last 10 years, it has been well documented that mineral metabolism abnormalities in dialysis patients are associated with an enhanced risk of morbidity and mortality for cardiovascular disease. Extraskeletal calcifications represent one of the major risk factors involved in the pathogenesis of cardiovascular disease in this population. In fact, secondary hyperparathyroidism and hyperphosphatemia associate with increased cardiovascular mortality in uremic patients for two reasons: first for the passive deposition of calcium and phosphate in soft tissues; second for the active role of inorganic phosphate on direct induction of extraskeletal mineralization of the tunica media in the vasculature of these patients. In peritoneal dialysis patients, many unbalances of calcium and phosphate metabolism are present. In particular, recent cohort studies indicate that most patients do not reach targets indicated by clinical practice guidelines. Further efforts to control hyperphosphatemia are essential, in order to reduce the impact of secondary hyperparathyroidism both on bone and cardiovascular system.
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PMID:Calcium and phosphate handling in peritoneal dialysis. 1672 Oct 13

Cardiovascular disease and stroke account for 60-70% of all deaths in patients with end-stage renal disease (ESRD), at a risk that is 10-20-fold the age- and sex-matched general population. There is also increased coronary artery calcification and increased cardiovascular mortality in chronic kidney disease (CKD) and dialysis patients compared with the general population. Bone is similarly abnormal in CKD. There is an increased incidence of low bone mass and fractures in dialysis patients compared with the general population. Furthermore, a hip fracture in a dialysis patient is associated with a doubling of the mortality observed in nondialysis patients with a hip fracture. These two problems may be linked, as cross-sectional studies have demonstrated an inverse relationship between osteoporosis and coronary artery calcification in the general population and in ESRD patients. In vitro and ex vivo, there is clear evidence that vascular calcification is an active cell-mediated process, made worse by disorders of mineral metabolism. Many factors known to be associated with cardiovascular disease in CKD patients can directly increase calcification in vitro. In addition, in CKD, there are many mechanisms by which bone may adversely affect vascular calcification including disorders of bone remodelling, altered secretion of parathyroid hormone (PTH), hyperphosphatemia, hypercalcaemia, use of calcium based binders, and excessive vitamin D therapy. The coexistence of vascular risk factors and abnormal bone represent a double threat to the well being of patients with CKD.
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PMID:Vascular calcification and renal osteodystrophy relationship in chronic kidney disease. 1688 98

Secondary hyperparathyroidism (SHPT) leads not only to bone disorders, but also to cardiovascular complications in long-term dialysis patients. Conventional treatment with calcium (Ca) supplement, phosphate (P) binders and active vitamin D analogs lead in part to amelioration of SHPT, but are simultaneously associated with unacceptable side-effects, including hypercalcemia, hyperphosphatemia, and increased Ca x P products, which are the risk factors for cardiovascular disease in dialysis patients. Conventional treatment has been unable to facilitate the attainment of optimal management of SHPT proposed in the K/DOQI guidelines. Cinacalcet HCl (cinacalcet), a novel calcimimetic compound, restores the sensitivity of the Ca-sensing receptor in parathyroid cells, and decreases serum parathyroid hormone (PTH) without introducing hypercalcemia or hyperphosphatemia. Cinacalcet treatment enables a significant number of patients to achieve the K/DOQI guideline. Based on experimental data, calcimimetics could ameliorate cardiovascular calcification and remodeling in uremic rats with SHPT. Clinical trials have shown that cinacalcet significantly reduced the risks of parathyroidectomy, fracture and cardiovascular hospitalization among long-term dialysis patients with SHPT. Parathyroid intervention therapy (parathyroidectomy and percutaneous direct injection) is also a useful alternative. In the present article, we review novel therapeutic strategies for SHPT.
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PMID:Therapeutic strategies for secondary hyperparathyroidism in dialysis patients. 1691 Nov 89

Cardiovascular disease occurs in ESRD patients at rates that are far higher than is seen in the general population, and cardiovascular deaths account for the majority of deaths among dialysis patients. Abnormal mineral metabolism is a novel cardiovascular risk factor among dialysis patients. Recently published results demonstrated that even with good control of BP and anemia, conventional hemodialysis is associated with significant left ventricular hypertrophy (LVH); however, daily hemodialysis was associated with a significant reduction in LV mass index (LVMI). Furthermore, it was shown that control of serum phosphorus correlates with the reduction in LVMI. These data suggest a novel mechanism for the deleterious effect of elevated serum phosphorus on cardiovascular outcomes among hemodialysis patients: LVH. Other investigators have noted an association of hyperphosphatemia and LVH; however, this study was the first to demonstrate that improvement in serum phosphorus is associated with reduction in LVM. In addition, it is shown that daily hemodialysis is an effective modality in improving serum phosphorus through significantly improved phosphorus removal. Elevated serum phosphorus leads to vascular calcification, which can lead to LVH by decreasing vascular compliance. However, our study showed an improvement in LVMI during a 12-mo period. Because vascular calcification is unlikely to remit over this time period, it is proposed that serum phosphorus has a reversible, cardiotoxic effect that leads to LVH that can be reversed successfully with good control of serum phosphorus.
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PMID:Left ventricular hypertrophy: is hyperphosphatemia among dialysis patients a risk factor? 1713 Feb 71

Hyperphosphatemia and hyperparathyroidism, frequently observed in patients with endstage renal disease, are associated with renal osteodystrophy, organ calcification, cardiovascular disease and sudden death. Restriction of dietary protein and phosphorus is beneficial in slowing the progression of renal failure. Dietary phosphorus restriction must be prescribed at all stages of renal failure in adults. It may be achieved by decreasing protein intake and avoiding foods rich in phosphorus. An average of 60-80% of the phosphorus intake is absorbed in the gut in dialysis patients. If phosphate binders are employed, the phosphorus absorbed from the diet may be reduced to 40%. Conventional hemodialysis with a high-flux, high-efficiency dialyzer removes approximately 30 mmol (900 mg) phosphorus during each dialysis performed three times weekly. Therefore, 750 mg of phosphorus intake should be the critical value above which a positive balance of phosphorus may occur. This value corresponds to a protein diet of 45-50 g/day or 0.8 g/kg body weight/day for a 60 kg patient. Target levels should become 9.2-9.6 mg/dl for calcium, 2.5-5.5 mg/dl for phosphorus, <55 mg2/dl2 for the calcium-phosphorus product, and 100-200 pg/ml for intact parathyroid hormone.
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PMID:Phosphate restriction in diet therapy. 1736 19

End-stage renal disease patients are at a heightened risk of developing cardiovascular disease, with contributions from both "traditional" and "nontraditional" cardiovascular risk factors. Some of the nontraditional risk factors, such as extracellular volume overload, inflammation, and hyperphosphatemia, have also been shown to be important predictors of mortality in the dialysis population. This article provides an in-depth review of the evidence that supports the substantial contributions of nontraditional risk factors to adverse cardiovascular outcomes in chronic peritoneal dialysis patients. In addition, it provides evidence to demonstrate how loss of residual renal function may be central to the development of cardiovascular disease in the peritoneal dialysis population.
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PMID:Cardiovascular risk factors in peritoneal dialysis patients revisited. 1755 9


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