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Albuminuria is recognized in all hypertension guideline statements as a cardiovascular risk factor and indicator of kidney disease. Recent data also demonstrate a strong association between the presence of microalbuminuria and elevations in C-reactive protein. Thus, the increased membrane permeability that generates microalbuminuria may be secondary to an inflammatory process. Progression from microalbuminuria (>30 and < or =300 mg albumin/g creatinine) to macroalbuminuria (>300 mg albumin/g creatinine) indicates a worsening of vascular disease and the presence of kidney disease. Recent outcome trials of kidney disease progression have demonstrated the best results among those with reductions in albuminuria in concert with blood pressure (BP) reduction. Thus, use antihypertensive agents that not only lower BP but also lower or normalize albuminuria levels. All recent guideline statements support the use of agents that block the renin-angiotensin-aldosterone system as part of a regimen to achieve the BP goal. Further lowering of albuminuria may be achieved by adding either a nondihydropyridine calcium antagonist such as verapamil or diltiazem, or aldosterone receptor blockers. Use of an angiotensin receptor blocker added to an angiotensin-converting enzyme inhibitor or vice versa can further lower albuminuria by an additional 30%-40%, which is not true of the additional lowering of BP.
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PMID:Implications of albuminuria on kidney disease progression. 1553 7

Chronic renal disease is generally appreciated as a major and rapidly growing health problem. In the United States alone, as many as 19.5 million people may have markers of early renal disease, and more than 660,000 people are expected to require renal replacement therapy by the year 2010. By contrast, the presence and pathological role of renal disease in patients with cardiovascular disease are somewhat underrecognized. Evidence now shows that even minor impairments in renal function, as indicated by measures including glomerular filtration rate and microalbuminuria, are common in cardiovascular disease states and predictive of cardiovascular events. Indeed, microalbuminuria may be a marker of systemic vascular disease rather than kidney dysfunction alone. In patients with hypertension, diabetes, metabolic syndrome, acute coronary syndromes, and stroke, markers of renal disease have proved to be at least as predictive of morbidity and mortality as conventional risk factors. Yet, chart reviews in a variety of clinical settings reflect poor recognition and management of renal disease in at-risk patients. Models for renal protection are based on the control of risk factors, particularly blood pressure, that are associated with renal and cardiovascular outcomes. Screening protocols for markers of renal disease should recognize the potential inaccuracy of serum creatinine concentrations and the preferability of glomerular filtration rate estimates that take age and gender into account. Pilot programs for screening high-risk populations have shown efficacy in detecting renal disease.
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PMID:Renal disease in cardiovascular disorders: an underrecognized problem. 1578 15

Both diabetes mellitus and hypertension are major risk factors for cardiovascular, renal and atherosclerotic vascular disease. Hypertension is known to be more common in patients with diabetes than in the general population. Patients with diabetes mellitus are at high risk for renal injury, which may be exacerbated by abnormalities in circadian blood pressure pattern. Ambulatory blood pressure monitoring (ABPM) permits the observation of blood pressure throughout day and night in a non-medical environment, and to quantify the circadian blood pressure variability. Recent studies with the use of ambulatory blood pressure monitoring have shown that the physiological nocturnal fall in blood pressure is blunted or absent in some individuals with type 1 diabetes who are completely normotensive by conventional criteria. Patients with type 1 diabetes and microalbuminuria have higher nocturnal blood pressure than either patients with type 1 diabetes and normal albumin excretion or age-matched controls. Moreover, changes in the circadian pattern of blood pressure in patients with type 1 diabetes may predict the development of albuminuria.
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PMID:[Changes in blood pressure and methods of blood pressure monitoring in patients with type-1 diabetes]. 1585 May 36

The endothelium is a complex organ with a multitude of properties essential for control of vascular functions. Dysfunction of the vascular endothelium is regarded as an important factor in the pathogenesis of diabetic micro- and macro-angiopathy. Endothelial dysfunction in Type I and II diabetes complicated by micro- or macro-albuminuria is generalized in that it affects many aspects of endothelial function and occurs not only in the kidney. The close linkage between microalbuminuria and endothelial dysfunction in diabetes is an attractive explanation for the fact that microalbuminuria is a risk marker for atherothrombosis. In Type I diabetes, endothelial dysfunction precedes and may cause diabetic microangiopathy, but it is not clear whether endothelial dysfunction is a feature of the diabetic state itself. In Type II diabetes, endothelial function is impaired from the onset of the disease and is strongly related to adverse outcomes. It is not clear whether impaired endothelial function is caused by hyperglycaemia or by other factors. Impaired endothelial function is closely associated with and may contribute to insulin resistance regardless of the presence of diabetes. Endothelial dysfunction in diabetes originates from three main sources. Hyperglycaemia and its immediate biochemical sequelae directly alter endothelial function or influence endothelial cell functioning indirectly by the synthesis of growth factors, cytokines and vasoactive agents in other cells. Finally, the components of the metabolic syndrome can impair endothelial function.
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PMID:Vascular complications in diabetes mellitus: the role of endothelial dysfunction. 1603 29

Hypertension and cardiovascular disease are leading causes of morbidity and mortality. Accumulating data demonstrate a relationship between hypertension and several vascular and metabolic abnormalities that are components of the cardiometabolic syndrome. The components of the cardiometabolic syndrome include insulin resistance/hyperinsulinemia, central obesity, dyslipidemia, hypertension, microalbuminuria, increased inflammation, and oxidative stress. There is growing evidence that tissue activation of the renin-angiotensin-aldosterone system participates in endothelial dysfunction, microalbuminuria, insulin resistance, and subsequent cardiovascular and chronic kidney disease. The notion that hypertension is a metabolic as well as a vascular disease opens a new paradigm for the treatment of this disorder.
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PMID:Hypertension and the cardiometabolic syndrome. 1610 58

The incidence of type-2 diabetes is increasing throughout the world. By 2010, 350 million people will have this disease. Microalbuminuria is present in more than one third, for some at diabetes diagnosis. Rather than a complication, it is an indication of a vascular disorder that is part of the metabolic syndrome. 25% will develop end-stage kidney failure. Several studies have identified microalbuminuria or proteinuria as an independent cardiovascular risk factor. Others have shown that antihypertensive treatments acting on the renin-angiotensin system (ACE inhibitors, ARBs agents) can reduce the progression of nephropathy in people with hypertension, type 2 diabetes and microalbuminuria. The "nephroprotective" effects of these drug classes, beyond their role in blood-pressure reduction, are suggested by modifications in renal structure and protein expression. But no study has so far examined their value in primary prevention in persons with type 2 diabetes without--but at risk of developing--microalbuminuria. The Roadmap study (Randomized Olmesartan And Diabetes Microalbuminuria Prevention Study) of primary prevention has as its objective measurement of the impact of ARBs (olmesartan 40 mg/d) treatment on renal outcome in 4400 patients with type 2 diabetes without microalbuminuria. Follow-up of this placebo-controlled study will last for 5 years. Conducted in 200 European centers, its results are expected for 2012.
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PMID:[Primary cardiorenal prevention in patients with type-2 diabetes. The Roadmap study]. 1626 93

A D/D (deletion/deletion) polymorphism within the ACE (angiotensin 1-converting enzyme) gene increases the risk of microalbuminuria, a predictor of atherosclerotic vascular disease, in essential hypertension. It is unknown, however, whether this genetic profile is accompanied by disturbed macromolecular permeability of systemic capillary endothelium, possibly in the context of generalized endothelial dysfunction. In the present study, the ACE gene polymorphism was determined by PCR in 79 never-treated uncomplicated hypertensive men and 16 normotensive men as controls. Evaluation variables were TERalb (transcapillary escape rate of albumin; the 1-h decline rate of intravenous (125)I-albumin, a measure of integrity of systemic capillary endothelium), albuminuria and forearm vasodilation to intra-arterial acetylcholine, an index of NO (nitric oxide)-mediated vasomotion, in addition to a series of sensitive parameters of albumin permeation (blood pressure, metabolic status and smoking habits). Analyses were done by comparing D/D homozygotes with grouped I/D (insertion/deletion) and I/I (insertion/insertion) subjects. TERalb was higher in D/D hypertensives, who had higher albuminuria, more frequent microalbuminuria and comparable forearm responsiveness to intra-arterial acetylcholine. Fasting glucose and insulin, insulin sensitivity, 24-h blood pressure, smoking habits and metabolic parameters did not differ between the two groups. TERalb and urine albumin values were positively associated in the hypertensive subjects. In conclusion, ACE D/D homozygosis, independently of several confounding factors, associates with higher TERalb in men with essential hypertension. This may reflect noxious genetic influences on systemic vascular permeability, a critical control mechanism for atherogenesis in the absence of grossly impaired NO-mediated arteriolar responsiveness. The parallel behaviour of TERalb and albuminuria suggests some shared genetically mediated determinant of renal and systemic microvascular abnormalities in hypertension.
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PMID:ACE gene insertion/deletion polymorphism modulates capillary permeability in hypertension. 1688 37

Microalbuminuria, originally described more than 3 decades ago as a predictor of nephropathy in patients who had type 1 diabetes mellitus and associated with higher cardiovascular risk, is now linked with increased risk for cardiovascular events rather than progression to end-stage kidney disease. This article reviews the role of microalbuminuria in the context of atherosclerotic vascular disease. It presents the methods for microalbuminuria assessment in clinical practice, its relations with other cardiovascular risk factors, and the pathophysiologic associations between microalbuminuria and vascular damage. In addition, this article discusses the prognostic significance of microalbuminuria for cardiovascular disease as well as existing therapeutic interventions for reducing urine albumin excretion in patients who are at high cardiovascular risk.
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PMID:Microalbuminuria. 1693 88

Hypertension (HTN) and type 2 diabetes mellitus (T2DM) are emerging as epidemics of the 21st century and are important components of the metabolic syndrome (MS). Evidence demonstrates a relationship between HTN, T2DM, and several vascular and metabolic abnormalities that are components of the MS. HTN affects nearly 70 million Americans and over one billion worldwide; likewise, the MS affects 44% of the US population above the age of 60 years and is rapidly increasing. HTN associated with the MS has certain pathophysiologic characteristics that provide clinical challenges. There is growing evidence that tissue activation of the renin-angiotensin system contributes to endothelial dysfunction, microalbuminuria, insulin resistance, and subsequent increased risk for cardiovascular and chronic kidney disease. The notion that HTN is a metabolic as well as a vascular disease provides a new treatment paradigm.
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PMID:Hypertension in people with diabetes and the metabolic syndrome: pathophysiologic insights and therapeutic update. 1754 38

To reduce the burden of cardiovascular disease (CVD), management strategies are increasingly focusing on preventive measures following early detection of markers of atherosclerosis. This review focuses on microalbuminuria, which is gaining recognition as a simple marker of an atherogenic milieu. Prospective and epidemiologic studies have found that microalbuminuria is predictive, independently of traditional risk factors, of all-cause and cardiovascular mortality and CVD events within groups of patients with diabetes or hypertension, and in the general population. The pathophysiologic mechanism underlying the association between albumin excretion and CVD is not fully defined. One hypothesis is that microalbuminuria may be a marker of CVD risk because it reflects subclinical vascular damage in the kidneys and other vascular beds. It may also signify systemic endothelial dysfunction that predisposes to future cardiovascular events. Based on this theory, periodic screening for microalbuminuria could allow early identification of vascular disease and help stratify overall cardiovascular risk, especially in patients with risk factors such as hypertension or diabetes. A positive test for urinary albumin excretion could signify the need for an intensive multifactorial intervention strategy, including behavior modification and targeted pharmacotherapy, aimed at preventing further renal deterioration and improving the overall CVD risk factor profile. Data from intervention studies suggest that treatment with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, statins, and/or strict glycemic control (in diabetics) offer significant reductions in cardiovascular and/or renal morbidity in patients with albuminuria. Use of this (old) marker may allow improved use of medications and strategies for secondary prevention.
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PMID:Microalbuminuria and cardiovascular disease. 1769 66


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