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Iranian Journal of Kidney Diseases May 2013Leakage of small amounts of proteins in urine has been considered since 1980s a crucial sign of early kidney disease, especially in diabetic patients. An increasing... (Review)
Review
Leakage of small amounts of proteins in urine has been considered since 1980s a crucial sign of early kidney disease, especially in diabetic patients. An increasing interest in microalbuminuria as a cardiovascular risk marker has been more recently considered. Many studies linked microalbuminuria to early cardiovascular disease, as a marker of endothelial dysfunction, not only in diabetic patients, but also in hypertensive patients and in general population. Microalbuminuria is considered nowadays by guidelines as a cost-effective marker of subclinical organ damage in hypertensive patients and should be checked routinely in hypertensive patients. Assessing subclinical organ damage is recommended not only at the level of screening, but also during treatment. Microalbuminuria is also considered as a treatment outcome marker and useful for understanding the ability of a given therapeutic intervention to regress organ damage or slow down its progression.
Topics: Albuminuria; Cardiovascular Diseases; Comorbidity; Diabetes Mellitus; Humans; Hypertension; Predictive Value of Tests; Prognosis; Risk Assessment; Risk Factors
PubMed: 23689147
DOI: No ID Found -
Current Opinion in Nephrology and... Nov 1997Microalbuminuria continues to receive attention in patients with hypertension, even if they do not have diabetes mellitus. The attention appears deserved, because... (Review)
Review
Microalbuminuria continues to receive attention in patients with hypertension, even if they do not have diabetes mellitus. The attention appears deserved, because microalbuminuria has emerged as an important risk factor for left ventricular hypertrophy, myocardial infarction, stroke, peripheral vascular disease and retinopathy, independent of blood pressure. Microalbuminuria may be a useful measurement during pregnancy and appears particularly indicated in following up women who develop pre-eclampsia during pregnancy. In addition to diabetes, increased blood pressure and age, the smoking habit appears to be the most important factor contributing to microalbuminuria, although other influences including uranium exposure have been implicated. We need to learn more about the mechanisms of microalbuminuria, particularly in non-diabetic hypertensive patients. Microalbuminuria is potentially reversible. All antihypertensive agents appear to reduce microalbuminuria. In diabetic patients, angiotensin-converting enzyme inhibitor therapy is effective in reducing renal disease progression, even in the absence of hypertension. Antioxidant therapy may be effective. Stopping smoking should be the initial antioxidant measure.
Topics: Albuminuria; Cardiovascular Diseases; Diabetes Mellitus; Female; Humans; Hypertension; Male; Pre-Eclampsia; Pregnancy
PubMed: 9375269
DOI: 10.1097/00041552-199711000-00010 -
Pediatric Nephrology (Berlin, Germany) Nov 2011Management strategies are increasingly focused on tackling the increasing burden of cardiovascular disease worldwide. Microalbuminuria is a powerful predictor of... (Review)
Review
Management strategies are increasingly focused on tackling the increasing burden of cardiovascular disease worldwide. Microalbuminuria is a powerful predictor of cardiovascular disease and mortality in adults. This holds true in the general adult population but is particularly recognized in those with diabetes, where it identifies those likely to develop progressive atherosclerotic vascular disease and renal impairment. The atherosclerotic process begins in childhood with likely consequences in later life. In-depth understanding of the mechanisms through which microalbuminuria occurs holds promise for designing therapies to arrest its development in the future. Microalbuminuria arises from increased leakage of albumin through the complex glomerular sieve known as the glomerular filtration barrier. This requires changes in the physio-chemical properties of components of this barrier. However, the increased glomerular permeability confirmed in disease does not necessarily correlate with recognized histological changes in the glomerulus, suggesting that perhaps more subtle ultrastructural changes may be relevant. The epidemiology of microalbuminuria reveals a close association between systemic endothelial dysfunction and vascular disease, also implicating glomerular endothelial dysfunction in microalbuminuria. This review discusses the mechanisms of microalbuminuria in disease, particularly the emerging role of the glomerular endothelium and its glycocalyx, and examines its implications for cardiovascular disease in the pediatric population.
Topics: Albuminuria; Child; Humans; Risk Factors
PubMed: 21301888
DOI: 10.1007/s00467-011-1777-1 -
Journal of Hypertension. Supplement :... Sep 1996Microalbuminuria is defined as abnormally elevated urinary albumin excretion below the level of clinical albuminuria (albustix). This represents a urinary albumin... (Review)
Review
DEFINITION
Microalbuminuria is defined as abnormally elevated urinary albumin excretion below the level of clinical albuminuria (albustix). This represents a urinary albumin excretion rate of 20-200 micrograms/min, equal to 30-300 mg/24 h. Urinary albumin excretion can vary as much as 40% with natural fluctuations, and so several tests should be done. Inexpensive radioimmunoassay, enzyme-linked immunosorbent assays or immunoturbidimetric assays are now routine in many clinical laboratories.
PREVALENCE
The prevalence of microalbuminuria in essential hypertension and diabetes is about the same: 25% (range 14-31) and 20% (9-27), respectively.
MECHANISMS
Increased transglomerular passage is the major mechanism of microalbuminuria in both the above-mentioned conditions; increased hydraulic glomerular capillary pressure and glomerular lesions probably both contribute. Microalbuminuria is highly predictive of the development of diabetic nephropathy but the predictive power in relation to hypertensive nephropathy remains to be established. However, in both conditions microalbuminuria is associated with an increased risk of retinopathy, left ventricular hypertrophy, fatal and non-fatal cardiovascular disease and all-cause mortality. The following mechanisms have been suggested as a link between microalbuminuria and these findings: endothelial dysfunction, insulin resistance, hyperinsulinemia, dyslipoproteinemia and a procoagulant state.
EFFECT OF ANTIHYPERTENSIVE TREATMENT
Blood pressure lowering reduces microalbuminuria in essential hypertension and in diabetes mellitus. Long-term studies in diabetes suggest that angiotensin converting enzyme inhibitors postpone, and may even prevent, progression to overt clinical nephropathy in normotensive diabetic patients with persistent microalbuminuria. So far, there have been no long-term comparative trials on the beneficial effects of different antihypertensive drugs in hypertensive patients with microalbuminuria.
Topics: Albuminuria; Antihypertensive Agents; Diabetes Mellitus; Humans; Hypertension
PubMed: 8934384
DOI: 10.1097/00004872-199609002-00017 -
Journal of Internal Medicine Jul 2003Microalbuminuria and hypertension with Over the past decade, there has been considerable focus on the concept of microalbuminuria, not only because it predicts renal... (Review)
Review
UNLABELLED
Microalbuminuria and hypertension with Over the past decade, there has been considerable focus on the concept of microalbuminuria, not only because it predicts renal disease in type 1 and type 2 diabetes, but also because it relates to premature mortality in the diabetic and in the general population. More importantly, intervention at this stage is now possible with the perspective of preserving glomerular filtration rate (GFR) and ameliorating cardiovascular disease and ensuing strong end-points. INITIAL STUDIES: The concept of microalbuminuria was introduced about 20 years ago and since then there has been a multitude of studies and papers on this subject using the original definition, but not always, in the US. Before that time it was suggested, mainly from the US, that diabetic renal disease was an untreatable relentlessly progressive condition.
GENETIC STUDIES
There is an overwhelming number of studies on genetics and diabetes and also covering the genetics of diabetic complications including nephropathy. However, so far the results are extremely disappointing. Patients at risk cannot be identified and genetic analyses are of no value as a guide to treatment. The notion that the development of complications is controlled mainly by a special genetic pattern is increasingly doubtful. In genetic studies, it is rather phenotypic well-accepted risk factors that dominate. STRUCTURAL BASIS OF MICROALBUMINURIA: Patients with microalbuminuria have significant abnormalities in the kidney, including glomeruli. This is quite clear in patients with type 1 diabetes, but is also seen in type 2 diabetes, where on the other hand, other risk factors such as hypertension and dyslipidaemia also seem to be of importance, including loss of autoregulation. Renal biopsies are generally not indicated in the management of diabetic patients. MICROALBUMINURIA AND EARLY MORTALITY: It is quite clear that microalbuminuria predicts early mortality both in type 1 and type 2 diabetes. The association to other risk factors may partly explain this--but this does not account for the whole picture. Endothelial dysfunction as well as inflammatory and arteriosclerotic abnormalities in blood vessels may be a relevant hypothesis that needs to be further explored along with other possibilities. CLINICAL COURSE AND ASSOCIATED ABNORMALITIES: The risk factor for progression in normoalbuminuric patients to microalbuminuria is higher than normal albumin excretion (strongest factor), poor glycaemic control, elevated blood pressure, and to some extent smoking. The clinical course of microalbuminuria is usually progressive, but with the more effective intervention now available we encounter that the so-called natural history (without intervention) is increasingly difficult to study. Microalbuminuria is clearly associated with a number of abnormalities, almost in all organs, but GFR is generally well preserved in spite of more advanced structural lesions. Therefore, microalbuminuria is an important marker for more pronounced diabetic vascular disease in general as well as for nephropathy. Regression to normoalbuminuria only rarely occurs during standard unchanged nonintensive treatment. TREATMENT STRATEGIES: The best possible glycaemic control is important in preventing and ameliorating the course of normo- and micro-albuminuria. Another major treatment strategy, especially in microalbuminuric patients, is antihypertensive treatment including inhibition of the renal angiotensin aldosterone system. Numerous new studies are available, both in type 1 and type 2 diabetes, documenting that not only microalbuminuria but also renal and cardiovascular complications in these patient are also far better controlled by early detection and treatment. Therefore, screening for microalbuminuria should be a strategy in all diabetes management followed by effective intervention as outlined in this paper.
Topics: Albuminuria; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diet, Protein-Restricted; Diet, Sodium-Restricted; Female; Humans; Hypertension; Male; Risk Factors
PubMed: 12823642
DOI: 10.1046/j.1365-2796.2003.01157.x -
Journal of Cardiovascular Pharmacology 2006A minor increase in urinary albumin excretion (microalbuminuria) is known to predict adverse renal and cardiovascular events in diabetic and hypertensive patients.... (Review)
Review
A minor increase in urinary albumin excretion (microalbuminuria) is known to predict adverse renal and cardiovascular events in diabetic and hypertensive patients. Recent intriguing findings show that microalbuminuria is an early and sensitive marker of future cardiovascular events even in healthy subjects. The mechanisms linking microalbuminuria with end-organ damage have not been fully explained yet; however, generalized endothelial dysfunction might play an important role. Prevailing experimental and clinical data suggest that generalized endothelial dysfunction, frequently characterized by decreased nitric oxide bioavailability, actually precedes the development of microalbuminuria. This review summarizes the current knowledge about the intricate relationship between microalbuminuria and endothelial dysfunction. On the basis of the current evidence, we propose that microalbuminuria and endothelial dysfunction are an emerging target for primary prevention strategies in cardiovascular disease. In near future, dietary components improving nitric oxide bioavailability, such as cocoa-derived flavanols may play important role in these preventive strategies.
Topics: Albuminuria; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Biomarkers; Capillary Permeability; Cardiovascular Diseases; Cell Adhesion Molecules; Diet; Endothelium, Vascular; Flavonoids; Humans; Kidney Failure, Chronic; Primary Prevention; Prognosis; Renin-Angiotensin System; Vasodilation; von Willebrand Factor
PubMed: 16794452
DOI: 10.1097/00005344-200606001-00009 -
International Journal of Clinical... Jan 2008Correlations between renal and cardiovascular (CV) pathologies in advanced kidney or heart disease are well characterised, but less clearly defined in the early stages.... (Review)
Review
INTRODUCTION
Correlations between renal and cardiovascular (CV) pathologies in advanced kidney or heart disease are well characterised, but less clearly defined in the early stages. Microalbuminuria, in addition to being an early sign of kidney damage, is often found in patients with essential hypertension, suggesting that it may reflect early vascular abnormalities.
EVIDENCE FROM LITERATURE
Studies have shown that even very low levels of microalbuminuria strongly correlate with CV risk: albumin excretion rates as low as 4.8 microg/min, well below the microalbuminuria thresholds stated in current clinical guidelines, are associated with increased risk of CV and cerebrovascular disease, independent of the presence of other risk factors. Increased microalbuminuria indicates endothelial dysfunction or developing atherosclerosis and predicts end-organ damage, major cardio or cerebrovascular events and death.
CLINICAL ASPECTS
Available tests for screening microalbuminuria are sensitive, reliable and accessible; current European and US guidelines advocate annual screening in patients with diabetes and wherever possible in non-diabetic patients with hypertension. Early identification of high-risk patients through detection of microalbuminuria allows selection of aggressive treatment to slow disease progression.
THERAPEUTIC IMPLICATIONS
Antihypertensive agents providing angiotensin II blockade are recommended for the treatment of hypertensive patients with microalbuminuria, regardless of diabetes and/or early or overt nephropathy. Treatment with angiotensin II receptor blockers provides effective reduction of microalbuminuria and blood pressure, and long-term prevention of CV events beyond blood pressure reduction. In addition, pharmacoeconomic studies have shown that these long-term benefits translate into a substantially reduced burden on healthcare resources.
Topics: Albuminuria; Antihypertensive Agents; Cardiovascular Diseases; Evidence-Based Medicine; Humans; Hypertension; Mass Screening
PubMed: 17971155
DOI: 10.1111/j.1742-1241.2007.01620.x -
Journal of Nephrology 1997Some patients with essential hypertension manifest increased urinary albumin excretion (UAE). Hypertensive patients with microalbuminuria manifest abnormal circadian... (Review)
Review
Some patients with essential hypertension manifest increased urinary albumin excretion (UAE). Hypertensive patients with microalbuminuria manifest abnormal circadian variation of blood pressure, increased serum levels of LDL-cholesterol and lipoprotein(a), a greater rise of serum insulin in response to an oral glucose tolerance test, and greater thickness of the carotid artery than patients without microalbuminuria. A 7 year follow-up of 141 hypertensive patients, 54 with microalbuminuria and 87 without microalbuminuria, we observed 12 cardiovascular events in patients with microalbuminuria and only 2 events in the patients with normal urine albumin excretion (P < 0.0002). Creatinine clearance decreased more in patients with microalbuminuria than in those with normal UAE. In conclusion, hypertensive individuals with microalbuminuria manifest a greater incidence of cardiovascular events and more decline in renal function than patients with normal UAE. We propose that measurements of UAE may be a useful marker for cardiovascular risk in patients with essential hypertension.
Topics: Albuminuria; Biomarkers; Blood Pressure; Carotid Stenosis; Circadian Rhythm; Cohort Studies; Creatinine; Follow-Up Studies; Glucose Tolerance Test; Humans; Hypertension; Insulin Resistance; Lipoproteins; Predictive Value of Tests; Prognosis; Retrospective Studies
PubMed: 9377730
DOI: No ID Found -
Journal of the American Society of... Nov 2002Microalbuminuria is defined as abnormal urinary excretion of albumin between 30 and 300 mg/d. It can be measured accurately by several widely available and sensitive... (Review)
Review
Microalbuminuria is defined as abnormal urinary excretion of albumin between 30 and 300 mg/d. It can be measured accurately by several widely available and sensitive methods. This abnormality can be found in 8 to 15% of nondiabetic patients with primary hypertension, although its prevalence varies greatly in the literature, likely due to differences in the methods used to detect it and to the criteria applied in the selection of patients. The pathogenetic mechanisms leading to the development of microalbuminuria are still not completely known. BP load and increased systemic vascular permeability, possibly due to early endothelial damage, seem to play a major role. Increased urinary albumin excretion has been associated with several unfavorable metabolic and nonmetabolic risk factors and subclinical hypertensive organ damage. In fact, a higher prevalence of concentric left ventricular hypertrophy and subclinical impairment of left ventricular performance, as well as the presence of carotid atherosclerosis, have been reported in patients with microalbuminuria. These associations might per se justify a greater incidence of cardiovascular events. Long-term longitudinal studies have recently confirmed the unfavorable prognostic significance of microalbuminuria in hypertensive patients. It has also been hypothesized that microalbuminuria might be a forerunner of overt renal damage in primary hypertension. Clinical studies, however, have shown conflicting results, and this hypothesis has to be considered tempting but speculative at present. In conclusion, microalbuminuria is a specific, integrated marker of cardiovascular risk and target organ damage in primary hypertension and one that is suitable for identifying patients at higher global risk. A wider use of this test in the diagnostic work-up of hypertensive patients is recommended.
Topics: Albuminuria; Cardiovascular Diseases; Humans; Hypertension; Kidney Diseases; Risk Factors
PubMed: 12466308
DOI: 10.1097/01.asn.0000032601.86590.f7 -
Journal of Human Hypertension Mar 2002Microalbuminuria (urinary albumin excretion equal to 30-300 mg/24 h) is a reliable indicator of premature cardiovascular mortality in diabetic patients and in the... (Review)
Review
Microalbuminuria (urinary albumin excretion equal to 30-300 mg/24 h) is a reliable indicator of premature cardiovascular mortality in diabetic patients and in the general population. In insulin-dependent and non-insulin-dependent diabetes mellitus microalbuminuria is a marker of initial diabetic nephropathy and predicts the evolution toward renal insufficiency. In essential hypertension the clinical and prognostic role of microalbuminuria is more controversial. While it is a recognised marker of cardiovascular complications and a reliable predictor of ischaemic heart disease, its prognostic value on the risk of progressive renal alterations is still uncertain because no prospective studies, taking microalbuminuria as a selection criterion and renal insufficiency as an end point, are available. Blood pressure control with antihypertensive drugs is accompanied by a reduction in urinary albumin excretion. The favourable effects of antihypertensive agents on microalbuminuria appear to be proportional to blood pressure reduction, but angiotensin-converting enzyme inhibitors and angiotensin-II-receptor antagonists show an additional beneficial effect on urinary albumin excretion. Whether the reduction of microalbuminuria obtained through pharmacological intervention has favourable prognostic implications remain to be demonstrated. However, screening for microalbuminuria is a relatively easy and inexpensive procedure and reveals a potentially treatable abnormality. Thus, considering that microalbuminuria identifies hypertensive subjects at higher risk than standard, urinary albumin excretion should be routinely measured in hypertensive patients and, in the presence of microalbuminuria, antihypertensive treatment should be intensified in order to obtain an optimal blood pressure control.
Topics: Albuminuria; Antihypertensive Agents; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Humans; Hypertension; Kidney Diseases; Risk Factors
PubMed: 11986900
DOI: 10.1038/sj.jhh.1001348