Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0028754 (obesity)
124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity-related glomerulopathy (ORG) is a secondary form of focal and segmental glomerulosclerosis (FSGS) occurring in severely obese patients. A significant percentage of individuals with ORG will develop renal insufficiency or end stage renal disease. We report here a 17-year-old girl with morbid obesity (body mass index 56.8 kg/m(2)) and ORG presenting with nephrotic range proteinuria, who failed to improve following treatment with diet, exercise and angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB) therapy. Laparoscopic gastric bypass surgery was performed, and within 2 weeks following the surgery, the patient had lost 5.7 kg body weight and showed a remarkable decrease in protein excretion to one tenth of pre-surgery levels. More than 1 year after surgery, the patient's urine protein and kidney function have remained normal while off renin-angiotensin system inhibition therapy. This is the first report of successful use of gastric bypass surgery for obesity-related glomerulopathy in an adolescent. We propose that gastric bypass surgery be considered for patients with ORG.
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PMID:Obesity-related focal and segmental glomerulosclerosis: normalization of proteinuria in an adolescent after bariatric surgery. 1894 98

Of the more than 5 million Americans who have heart failure (HF), 30% to 50% have HF with preserved ejection fraction (HF-PEF). HF-PEF commonly occurs in elderly patients, especially women, with comorbidities of hypertension, left ventricular hypertrophy, diabetes, myocardial ischemia, and obesity. HF-PEF is associated with high morbidity and mortality. Although two large multicenter randomized, placebo-controlled trials evaluating an angiotensin-converting enzyme inhibitor (ACEI) and an angiotensin receptor blocker (ARB) in patients with HF-PEF did not demonstrate any statistically significant benefit in their primary end points, they did suggest that these agents may have a modest role in reducing HF hospitalizations. Although calcium channel blockers and beta-blockers may be of benefit in patients with HF-PEF, large clinical trial data are not available to support their routine use in all patients with HF-PEF. Subgroup analysis does not support the use of digoxin in patients with HF-PEF in sinus rhythm. Current therapeutic recommendations for HF-PEF are aimed at 1) management of HF symptoms with sodium and fluid restriction along with diuretics for volume overload and 2) treatment of concomitant comorbidities, especially hypertension, rate and possibly rhythm control of atrial fibrillation, and evaluation and treatment of myocardial ischemia and anemia. ACEIs, ARBs, calcium channel blockers, and beta-blockers are recommended for HF-PEF patients who have other established indications for their use. Results are awaited from ongoing clinical trials with another ARB, irbesartan, and an aldosterone blocker, spironolactone.
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PMID:Treatment of patients with heart failure and preserved ejection fraction. 1902 82

Obesity is closely associated with development of hypertension. Adipose tissue produces molecules of renin-angiotensin system, which contribute to metabolic as well as cardiovascular disorders that develop in obesity. CASE-J Study demonstrated the usefulness of angiotensin receptor blockade in preventing new onset diabetes in obese hypertensive patients.
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PMID:[Obesity in CASE-J Study]. 1920 19

The pathological mechanisms of out-of-office hypertension (e.g., masked hypertension and workplace hypertension) have been remained unclear, but several mechanisms for this unique phenomenon have been proposed. Altered neurohumoral regulations, increased activity of sympathetic nerve and renin-angiotensin-system (RAS), and reduced baroreflex gain, coupled to a prolonged endothelial dysfunction, play an important role in out-of-office hypertension. Previous studies showed that angiotensin receptor blocker (ARB) reduced not only RAS but also sympathetic activity, and improved baroreflex as well asendothelial function, which suggested that ARB may be suitable for treating subjects with out-of-office hypertension. In the TROPHY (TRial Of Preventing HYpertension) study, it has been demonstrated that treatment with ARB reduced the risk of development of true hypertension from a pre-hypertensive state. Because there were close associations between pre-hypertension and out-of-office hypertension, especially in those with obesity and metabolic syndrome, this study may also provide an important information about the treatment strategy of out-of-office hypertension.
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PMID:[The clinical utility of angiotensin receptor blockers in out-of-office hypertension (masked hypertension, workplace hypertension, and home hypertension)]. 1934 44

Diabetes mellitus and hypertension frequently coexist in patients with the insulin resistance syndrome (IRS). Patients with both diabetes and hypertension typically have widespread endothelial dysfunction, increased oxidative stress, an activated sympathoadrenal system, and an elevated systemic burden of inflammatory mediators. Patients with diabetes and hypertension also have concomitant mixed dyslipidemia and obesity with significant frequency, and are at high risk for the development of macro- and microvascular disease, congestive heart failure, and nephropathy. Current data suggest that ACE inhibitors or angiotensin receptor blockers with or without a diuretic are important, if not preferred, initial therapies for the patient with diabetes and hypertension. Other drug classes such as combined alpha-/beta-adrenoceptor antagonists, dihydropyridine calcium channel antagonists (CCAs), and peripheral alpha-adrenoceptor antagonists are also useful therapeutic options in these patients. In order to optimally reduce the risk for cardiovascular events in the patient with diabetes and hypertension, optimal BP control should be coupled with comprehensive lifestyle modification and aggressive management of dyslipidemia and hyperglycemia.
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PMID:A guide to the management of blood pressure in the diabetic hypertensive patient. 1946 21

Limited contemporary data exist on the cardiovascular risk of patients with prior coronary artery bypass grafting surgery (CABG) requiring diagnostic coronary angiography. We examined the prevalence and control of coronary artery disease risk factors and the outcomes of 367 prior CABG patients who underwent diagnostic coronary angiography between October 1, 2004 and May 31, 2007 at the Dallas Veterans Affairs Medical Center. Mean age was 65 +/- 9 years, 97% were men, and the mean time from CABG to diagnostic angiography was 8.2 +/- 6.1 years. Hypertension, low-density lipoprotein cholesterol, diabetes mellitus, smoking, and obesity were suboptimally controlled in 70%, 59%, 47%, 33%, and 50%, respectively. Intake of statins and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was 88% and 81%, respectively. After a mean follow-up of 1.4 +/- 0.8 years, the incidence of death and major cardiovascular events was 10% and 32%, respectively. In spite of significant improvement compared to previous studies and good compliance with indicated medications, contemporary prior CABG patients undergoing coronary angiography still have multiple and poorly controlled coronary artery disease risk factors and high risk for cardiovascular events. Novel pharmacologic and behavioral treatment strategies are needed.
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PMID:Prior coronary artery bypass graft surgery patients undergoing diagnostic coronary angiography have multiple uncontrolled coronary artery disease risk factors and high risk for cardiovascular events. 1962 94

Microalbuminuria-increased urinary albumin excretion undetectable by traditional urinary dipstick-has been associated with insulin resistance, diabetes mellitus, obesity, and hypertension. It is also a powerful predictor for heart disease and all-cause mortality. In diabetic patients, microalbuminuria has been correlated with the progression of diabetic nephropathy and the development of renal insufficiency. Furthermore, its correlation with markers of inflammation such as C-reactive protein suggests that microalbuminuria may indicate generalized endothelial dysfunction rather than isolated nephropathy. Drugs that block the renin-angiotensin system, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), have been shown to reduce albuminuria, resulting in renal protection. Recently, dualaction beta-adrenergic blockers such as carvedilol have been shown to exert favorable effects on albuminuria in diabetic patients with hypertension. Insulin resistance reflects a predictable risk for diabetes, and there appears to be a good correlation between insulin resistance, albuminuria, and progression of renal disease in diabetes with or without hypertension. As in microalbuminuria, ACE inhibitors, ARBs, and dual-action beta-blockers help improve insulin sensitivity.
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PMID:Microalbuminuria, insulin resistance, diabetes, hypertension, and kidney function: the latest concepts in pathology and pharmacologic treatment. 1966 9

Non-immunological factors in the progression of kidney disease in transplant patients are the following: high blood pressure, proteinuria, dislypidemia, etc. 1. Arterial hypertension treatment: Blood pressure must be measured periodically in all transplant patients. Similarly to native kidneys, in renal transplant patients arterial hypertension is a risk factor in the progression of kidney disease. Arterial hypertension represent a clinical marker of chronic allograft nephropathy and contributes to graft loss and to the morbid- mortality of these patients (Evidence level C). Blood pressure control should be < 130/80 mm Hg for renal transplant patients without proteinuria and 125/75 mm Hg for proteinuric patients (> 1 g/24 hours). Hypertension and proteinuria are frequently associated in the same patients, a global treatment of both seems more rational (Evidence level C). General measures should be instigated first with pharmacological therapy. All antihypertensive drugs are useful in renal transplant patients and the majority of patients will need two or more drugs. In proteinuric patients an angiotensin receptor antagonist or an ACE-inhibitor should be initiated. It is advisable to monitor the serum potassium and creatinine after the start of this drugs or during the treatment periodically, especially in patients with chronic kidney disease stage IV-V. 2. Proteinuria treatment: Proteinuria has been strongly correlated with reduced function and graft survival. Lowering proteinuria to values as near to normal as possible (< 0.5 g/24 hours). To reduce proteinuria, an angiotensin receptor antagonist, an ACE-inhibitor or a combination of both are required, with serum potassium or creatinine monitoring, especially in patients with chronic kidney disease stage IV-V. 3. Dyslipidemia treatment: For kidney transplant recipients the assessment of dyslipidemias should include a complete fasting lipid profile with total cholesterol, LDL, HDL, and triglycerides. Evidence from the general population indicates that treatment of dyslipidemias reduces cardiovascular disease and evidence in kidney transplant patients suggests that judicious treatment can be safe and effective in improving dyslipidemia. Therapeutic goal must be LDL < 100 mg/dl. (Evidence level C). 4. Others: Cigarette smoking, glucose intolerance or diabetes control and obesity should be assessed.
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PMID:[Progression factors in chronic kidney disease. Non-immunological mechanisms]. 1967 57

Valsartan is a nonpeptide angiotensin receptor antagonist that selectively blocks the binding of angiotensin II to the angiotensin II type 1 receptor. The efficacy, tolerability and safety of valsartan have been demonstrated in large-scale studies in hypertension, heart failure (HF) and post-myocardial infarction (MI). This review focuses on what was learned from the valsartan clinical research programme and other comparative trials published from 1997 to the present. Many studies have demonstrated the efficacy of valsartan in lowering blood pressure (BP) in a variety of patient populations (including elderly, women, children, obese patients, patients with diabetes mellitus, patients with chronic kidney disease [CKD], patients at high risk of cardiovascular [CV] disease, African Americans, Hispanic Americans and Asians) and in improving outcomes in CV disease and CKD. In hypertension, valsartan exhibits dose-dependent efficacy in reducing both systolic and diastolic BP over the once-daily dose range of 80-320 mg; doses as high as 640 mg/day have been studied and found to be efficacious and safe. BP control can be enhanced with a more consistent 24-hour BP-lowering profile by using single-pill, fixed-dose combination therapy with valsartan plus hydrochlorothiazide (HCTZ). The cardioprotective benefits of valsartan have been demonstrated in large-scale outcome trials and include significant reductions in CV morbidity and mortality in HF, following MI, and in patients with co-morbid hypertension and coronary artery disease and/or HF; reductions in HF hospitalizations; and reductions in the incidence of stroke. The magnitude of these effects is comparable with that demonstrated with angiotensin-converting enzyme (ACE) inhibitors; however, valsartan has a more favourable tolerability profile, with a significantly lower incidence of cough and only rare reports of angio-oedema, both class effects of ACE inhibitor use. Consistent with its angiotensin receptor-blocking effects, valsartan also reduces circulating levels of biochemical markers that are associated with angiotensin II-mediated endothelial dysfunction and CV risk (e.g. high-sensitivity C-reactive protein or oxidized low-density lipoprotein). Improvements in CKD with valsartan include statistically and clinically meaningful reductions in urinary albumin and protein excretion in patients with type 2 diabetes and in nondiabetic patients with CKD. In short-term studies, valsartan has improved or stabilized various indices of metabolic function in at-risk patients, including those with co-morbid hypertension, obesity and/or metabolic syndrome. Because of this, valsartan is being prospectively investigated for its ability to reduce the incidence of new-onset diabetes and provide cardioprotection in patients with impaired glucose tolerance. Valsartan and valsartan/HCTZ are well tolerated. In clinical trials, adverse events during valsartan treatment were similar to those occurring with placebo. The combination of valsartan/HCTZ was better tolerated than HCTZ alone. Valsartan is administered once daily for hypertension; doses are usually taken upon awakening. In patients with HF or MI, valsartan is administered twice daily.
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PMID:Valsartan: more than a decade of experience. 1991 55

Obesity is fast becoming a bane for the present civilization, as a result of sedentary lifestyle, atherogenic diet, and a susceptible thrifty genotype. The concept of metabolic syndrome, which is a constellation of metabolic disturbances, has crystallized over the last 80 years with the aim of identifying those at greater risk of developing type 2 diabetes and cardiovascular disease. These patients have visceral obesity and insulin resistance characterized by hypertyriglyceridemia. Recently, it has been realized that they are also at an increased risk of chronic renal disease. Release of adipocytokines leads to endothelial dysfunction. There is also activation of systemic and local renin-angiotensin-aldosterone system, oxidative stress, and impaired fibrinolysis. This leads to glomerular hyperfiltration, proteinuria, focal segmental glomerulosclerosis (FSGS), and ultimately end-stage renal disease (ESRD). Treatment consists of lifestyle modifications along with optimal control of blood pressure, blood sugar and lipids. Metformin and thiazolidenidiones reduce insulin resistance; while angiotensin converting enzyme inhibitors and angiotensin receptor blockers reduce proteinuria and have a renoprotective effect. Exciting new medical therapies on the horizon include rimonabant a cannabinoid receptor type 1 antagonist, soy proteins, and peroxisome proliferator-activated receptor (PPAR) agonist. Bariatric surgery for morbid obesity has also been shown to be effective in treating metabolic syndrome.
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PMID:Metabolic syndrome and chronic kidney disease. 2036 11


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