Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The interlinking of CVD with CKD is undeniable. CVD accounts for more than 50% of all morbidity and mortality in patients with kidney disease who have undergone renal replacement therapy, and CVD is also prevalent in patients with mild and moderately severe kidney disease. To help address the elevated risks of these patients, primary care physicians need to maintain vigilance in (1) identifying patients who have CKD and (2) implementing strategies for reducing the prevalence of CVD in this population. It is essential that patients be screened for relatively mild kidney disease by measurement of serum creatinine and urine microalbumin and by calculation of the glomerular filtration rate in mL/min/1.73 m2 using equations based on serum creatinine. Rigorous assessment of conventional risk factors, including dyslipidemia, hypertension, and diabetes, is also necessary to prevent the poor outcomes currently observed in persons with CKD. Routine use of ACE inhibitors and aspirin is encouraged in all patients with CKD, and strict glycemic and blood pressure control is recommended for optimal outcomes. In addition, patients should be screened and treated for risk factors particularly associated with kidney disease and CVD morbidity and mortality, including anemia, hyperphosphatemia, and hyperparathyroidism. Finally, physicians should be careful to avoid therapeutic nihilism in patients with kidney disease; those at highest risk of CVD are likely to receive the greatest benefit from cardiovascular therapies.
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PMID:Cardiovascular disease and the kidney. Tracking a killer in chronic kidney disease. 1198 33

Vascular calcification is a frequent complication of uremic patients. In addition to classical risk factors such as age, male gender, smoking, inflammation, hypertension, dyslipidemia, and diabetes, which also exist in the general population, patients with chronic renal failure have other risk factors such as oxidative stress, inflammation, hyperparathyroidism, hypoparathyroidism, hypercalcemia, hyperphosphatemia, and overtreatment with calcium and vitamin D. These latter risk factors may even have a better predictive value than classical risk factors for coronary heart disease in uremic patients.
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PMID:Advanced oxidation protein products, parathyroid hormone and vascular calcification in uremia. 1220 1

Arteriosclerosis, atherosclerosis and vascular calcification are causally related to the high morbidity and mortality of patients with chronic renal failure. Oxidative stress and carbonyl stress of uremia, dialysis procedure and/or intravenous iron therapy result in AGE (advanced glycation end-product), ALE (advanced lipoxidation end-product) and AOPP (advanced oxidation protein product) formation, favouring together with elevated CRP (C-reactive protein) levels the development of cardiovascular and cerebrovascular complications. Enhanced plasma levels of homocysteine and ADMA (asymmetric dimethylarginine) contribute to this process. In addition, in chronic renal insufficiency hyperphosphatemia and an enhanced calcium x phosphorus ion product are associated with the morbidity and mortality of the patients, particularly in the presence of fetuin deficiency. Phosphorus, AGEs and AOPPs, beside other factors, catalyze the conversion of vascular smooth muscle cells to osteoblast--like cells (particularly in the presence of monocytes/macrophages), resulting in bone matrix protein formation. Other risk factors, such as age, male sex, smoking, hypertension, diabetes, chronic inflammation, insulin resistance or dyslipidemia (enhanced non-HDL-cholesterol) also contribute to the atherosclerotic risk profile of the patient with chronic renal insufficiency. While there is growing understanding of the mechanisms involved in arteriosclerosis, atherosclerosis and vascular calcification in uremia, we are still missing effective therapeutic maneuvers for reduction of excess mortality in uremic patients.
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PMID:[Atherosclerosis and uremia: signifance of non-traditional risk factors]. 1277 74

Hyperphosphatemia and dyslipidemia are common clinically significant conditions in end-stage renal disease (ESRD). Hyperphosphatemia management is essential; however, use of calcium-based phosphate binder has been associated with elevated risk of cardiac calcification in ESRD, increasing risks for cardiovascular disease and death. An alternative to calcium-based phosphate binders is sevelamer hydrochloride, a calcium-free, metal-free, nonabsorbed polymer that binds phosphate effectively. We conducted a meta-analysis on the effects of sevelamer hydrochloride on parameters of mineral metabolism (serum phosphorous, calcium, Ca x P, and iPTH) and the lipid profile (total, LDL, HDL, and non-HDL cholesterol, and triglycerides) in dialysis patients. After application of inclusion/exclusion criteria, 17 core studies were statistically analyzed to determine the sevelamer treatment effect on the study parameters as demonstrated by simple, n-weighted, and inverse variance-weighted mean changes. Analysis of inverse variance-weighted mean changes indicated that sevelamer treatment was associated with a 2.14 mg/dL drop in serum phosphorus (P <.001), no significant overall effect on calcium (0.09 mg/dL, P =.364), significant decline in Ca x P product (15.91 mg(2)/dL(2), P <.001), 35.99 pg/mL reduction in iPTH (P =.026), significant reduction in total cholesterol (30.58 mg/dL, P <.001), 31.38 mg/dL drop in LDL cholesterol (P <.001), significant increase in HDL cholesterol (4.09 mg/dL, P =.008), and a significant reduction in triglycerides (22.04 mg/dL, P x.001). This meta-analysis suggests that sevelamer offers a dual therapeutic benefit in dialysis patients-a population at high risk for cardiovascular disease-by improving phosphorus control and the lipid profile, without altering serum calcium.
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PMID:Meta-analysis of the effect of sevelamer on phosphorus, calcium, PTH, and serum lipids in dialysis patients. 1287 74

Hyperlipidemia is a secondary disorder associated with many metabolic disorders including hypothyroidism. The occurrence of dyslipidemia in subclinical hypothyroidism is controversial. Hyperphosphatemia may accompany the dyslipidemia in some metabolic disorders. Both hyperlipidemia and hyperphosphatemia are considered to be risk factors for the coronary heart diseases. In the present study, we investigated the occurrence of dyslipidemia and altered serum phosphate concentrations in patients with thyroid disorders. The results indicated a significantly elevated serum cholesterol and triglyceride concentrations in the hypothyroid patients. The dyslipidemia was accompanied with significantly elevated serum phosphate level. On the other hand, no significant difference was evident in the serum lipid or phosphate concentrations of subclinical hypothyroid patients compared to euthyroid subjects. A significantly reduced serum phosphate level was shown in hyperthyroid patients with unaltered serum lipid levels. Significant correlations were evident between TSH and T(4) levels as independent parameters and the serum concentrations of triglyceride, cholesterol and phosphate. The results indicate in hypothyroidism that a secondary hyperphosphatemia may aggravate myocardial and arterial abnormalities induced by the secondary hyperlipidemia, which may need correction.
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PMID:The secondary dyslipidemia and deranged serum phosphate concentration in thyroid disorders. 1501 Feb 97

Vascular calcifications are more frequent in dialysis patients than in the general population or in patients with cardiovascular disease (CVD) and normal renal function. The reasons for this high incidence are multiple; they include traditional factors such as hypertension, diabetes, dyslipidemia, and specific factors such as sodium overload, hyperomocysteinemia, chronic inflammation and oxidative stress, as well as mineral metabolism disturbances. Specifically, hyperphosphatemia and the elevated calcium (Ca) x phosphate product have been associated with an increased risk for the development of vascular calcification and death. Treatment with Ca salts can induce hypercalcemia, increased Ca x phosphate product and Ca overload. Sevelamer substitution for Ca salts has been documented to attenuate the progression of coronary artery and aortic calcification. A possible mechanism explaining this observation could be ongoing Ca loading related to oral Ca ingestion. Treatment with Ca salts could induce Ca overload, particularly in patients dialyzed against a high dialysate Ca (>1.5 mmol/L) solution, which is known to determine a positive dialysis balance. Conversely, an overall negative Ca balance can result from low Ca dialysate use (1.25 mmol/L) when the patients do not receive Ca supplements or vitamin D metabolites. Maintaining normal Ca and phosphate balances remains a primary goal in the management of dialysis patients. Control of hyperphopshataemia should be achieved either using Ca and aluminum-free phosphate binders, such as sevelamer, or Ca salts, alone or in combination, provided that a daily oral elemental Ca intake of 1.5 g is not exceeded.
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PMID:[Control of calcium and phosphate metabolism and prevention of vascular calcifications in uremic patients]. 1578 2

We have shown that renal injury and chronic kidney disease (CKD) directly inhibit skeletal anabolism, and that stimulation of bone formation decreases the serum phosphate. Most recently, these observations were rediscovered in low-density lipoprotein receptor null mice fed high-fat/cholesterol diets, a model of the metabolic syndrome (hypertension, obesity, dyslipidemia, and insulin resistance). We had demonstrated that these mice have vascular calcification (VC) of both the intimal atherosclerotic type and medial type. We have shown that VC is worsened by CKD and ameliorated by bone morphogenetic protein -7 (BMP-7). The finding that high-fat-fed low-density lipoprotein receptor null animals without CKD have hyperphosphatemia led us to examine the skeletons of these mice. We found significant reductions in bone formation rates, associated with increased VC and superimposing CKD results in the adynamic bone disorder (ABD), while VC was worsened and hyperphosphatemia persisted. A pathological link between abnormal bone mineralization and VC through the serum phosphorus was demonstrated by the partial effectiveness of directly reducing the serum phosphate by a phosphate binder that had no skeletal action. BMP-7 treatment corrected the ABD and corrected hyperphosphatemia, compatible with BMP-7-driven stimulation of skeletal phosphate deposition reducing plasma phosphate and thereby removing a major stimulus to VC. Thus, in the metabolic syndrome with CKD, a reduction in bone-forming potential of osteogenic cells leads to ABD producing hyperphosphatemia and VC, processes ameliorated by the skeletal anabolic agent BMP-7, in part through increased bone formation and skeletal deposition of phosphate, and in part through direct actions on vascular smooth muscle cells. We have demonstrated that the processes leading to vascular calcification begin with even mild levels of renal injury before demonstrable hyperphosphatemia, and they are preventable and treatable. Therefore, early intervention in CKD is warranted and may affect mortality of the disease.
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PMID:Connections between vascular calcification and progression of chronic kidney disease: therapeutic alternatives. 1633 68

Vascular calcification increasingly afflicts our aging and dysmetabolic population. Once considered a passive process, it has emerged as an actively regulated form of calcified tissue metabolism, resembling the mineralization of endochondral and membranous bone. Executive cell types familiar to bone biologists, osteoblasts, chondrocytes, and osteoclasts, are seen in calcifying macrovascular specimens. Lipidaceous matrix vesicles, with biochemical and ultrastructural "signatures" of skeletal matrix vesicles, nucleate vascular mineralization in diabetes, dyslipidemia, and uremia. Skeletal morphogens (bone morphogenetic protein-2 (BMP) and BMP4 and Wnts) divert aortic mesoangioblasts, mural pericytes (calcifying vascular cells), or valve myofibroblasts to osteogenic fates. Paracrine signals provided by these molecules mimic the epithelial-mesenchymal interactions that induce skeletal development. Vascular expression of pro-osteogenic morphogens is entrained to physiological stimuli that promote calcification. Inflammation, shear, oxidative stress, hyperphosphatemia, and elastinolysis provide stimuli that: (1) promote vascular BMP2/4 signaling and matrix remodeling; and (2) compromise vascular defenses that limit calcium deposition, inhibit osteo/chondrogenic trans-differentiation, and enhance matrix vesicle clearance. In this review, we discuss the biology of vascular calcification. We highlight how aortic fibrofatty tissue expansion (adventitia, valve interstitium), the adventitial-medial vasa, vascular matrix, and matrix vesicle metabolism contribute to the regulation of aortic calcium deposition, with greatest emphasis placed on diabetic vascular disease.
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PMID:Molecular mechanisms of vascular calcification: lessons learned from the aorta. 1660 Dec 33

In two independent and separate studies, we have shown that renal injury and chronic kidney disease (CKD) directly inhibit skeletal anabolism, and that stimulation of bone formation decreased the serum phosphate. In the first study, the serum Ca PO(4), parathyroid hormone (PTH), and calcitriol were maintained normal after renal ablation in mice, and even mild renal injury equivalent to stage 3 CKD decreased bone formation rates. More recently, these observations were rediscovered in low-density lipoprotein receptor null (LDLR-/-) mice fed high-fat/cholesterol diets, a model of the metabolic syndrome (hypertension, obesity, dyslipidemia and insulin resistance). We demonstrated that these mice have vascular calcification (VC) of both the intimal atherosclerotic type and medial calcification. We have also shown that VC is made worse by CKD and ameliorated by bone morphogenetic protein-7 (BMP-7). The finding that high-fat fed LDLR-/- animals with CKD had hyperphosphatemia which was prevented in BMP-7-treated animals lead us to examine the skeletons of these mice. It was found that significant reductions in bone formation rates were associated with high-fat feeding, and superimposing CKD resulted in the adynamic bone disorder (ABD), while VC was made worse. The effect of CKD to decrease skeletal anabolism (decreased bone formation rates and reduced number of bone modelling units) occurred despite secondary hyperparathyroidism. The BMP-7 treatment corrected the ABD and hyperphosphatemia, owing to BMP-7-driven stimulation of skeletal phosphate deposition reducing plasma phosphate and thereby removing a major stimulus to VC. A pathological link between abnormal bone mineralization and VC through the serum phosphorus was demonstrated by the partial effectiveness of directly reducing the serum phosphate by a phosphate binder that had no skeletal action. Thus, in the metabolic syndrome with CKD, a reduction in bone forming potential of osteogenic cells leads to the ABD producing hyperphosphatemia and VC, processes ameliorated by BMP-7, in part through increased bone formation and skeletal deposition of phosphate and in part through direct actions on vascular smooth muscle cells. We have demonstrated that the processes leading to vascular calcification begin with even mild levels of renal injury affecting the skeleton before demonstrable hyperphosphatemia and that they are preventable and treatable. Therefore, early intervention in the skeletal disorder associated with CKD is warranted and may affect mortality of the disease.
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PMID:Function and effect of bone morphogenetic protein-7 in kidney bone and the bone-vascular links in chronic kidney disease. 1688 97

Systemic fungal infections are increasingly reported in immunocompromised patients with hematological malignancies, recipients of bone marrow and solid organ allografts, and patients with AIDS. Mycoses may infiltrate endocrine organs and adversely affect their function or produce metabolic complications, such as hypopituitarism, hyperthyroidism or hypothyroidism, pancreatitis, hypoadrenalism, hypogonadism, hypernatremia or hyponatremia, and hypercalcemia. Antifungal agents used for prophylaxis and/or treatment of mycoses also have adverse endocrine and metabolic effects, including hypoadrenalism, hypogonadism, hypoglycemia, dyslipidemia, hypernatremia, hypocalcemia, hyperphosphatemia, hyperkalemia or hypokalemia, and hypomagnesemia. Herein, we review how mycoses and conventional systemic antifungal treatment can affect the endocrine system and cause metabolic abnormalities. If clinicians are equipped with better knowledge of the endocrine and metabolic complications of fungal infections and antifungal therapy, they can more readily recognize them and favorably affect outcome.
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PMID:Endocrine and metabolic manifestations of invasive fungal infections and systemic antifungal treatment. 1877 5


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