Microalbuminuria

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.     

Microalbuminuria: marker or maker of cardiovascular disease

Advancing age is associated with albuminuria and vascular changes. This review will explore the putative links between the two. Vascular ageing involves endothelial dysfunction as well as increased arterial diameter, wall thickness and stiffness, ultimately leading to arterial sclerosis. This process is accelerated by a defective vascular repair process. Endothelial dysfunction is likely to be involved in the initiation and development of microalbuminuria. It is often followed by the development and progression of atherosclerosis. Initially, microalbuminuria is reversible but becomes fixed with the progression of vascular structural changes including glomerulosclerosis. The prevalence of microalbuminuria increases with age and has been shown to be a marker of widespread microvasculopathy at various levels including cerebral, cardiac and renal microcirculations. This has been linked to endpoint clinical events, with microalbuminuria increasing the risk of cognitive impairment and strokes, cardiovascular disease outcomes, and progression to end-stage renal failure. Evidence of microvascular damage such as microalbuminuria associated with increased cardiovascular risk may suggest that microvascular damage and dysfunction predate overt macrovascular disease. Microalbuminuria and reduced glomerular filtration rate (GFR) may be markers of different pathologic processes. It is likely that microalbuminuria and reduced GFR simply represent, respectively, the spectrum of renal vascular manifestations from systemic endothelial dysfunction (microvascular disease) to systemic atherosclerosis (macrovascular disease).     

Albuminuria: an indicator of cardiovascular risk]

BACKGROUND: The transition of albumin from the vascular lumen into the surrounding tissue always indicates a serious disturbance of the vascular wall. Clinically, this process can be recognized as "cotton-wool" spots of the retina or by testing the urine for the presence of albumin. The appearance of albumin in the urine is pathologic and should be evaluated within the context of the accompanying cardiovascular risk. PATHOPHYSIOLOGY AND DEFINITIONS: Albumin transition is indicative of a disturbance of the barrier function of endothelial cells. In the kidney, damage to podocytes, mesangial and endothelial cells, a loss of charge selectivity, and an altered expression of matrix proteins can be observed. However, vascular alterations are not confined to the kidney but can also be observed in the myocardium. Even though thresholds for microalbuminuria (> 30 mg/24 h) and proteinuria (> 300 mg/24 h) have been arbitrarily defined, an increase in risk starts at much lower levels of albumin excretion. PREVALENCE AND PROGNOSTIC IMPORTANCE: The prevalence of microalbuminuria in the general population is about 8%. However, prevalence rates of > 50% have been observed in high-risk groups, which are accompanied by an increased risk for cardiovascular morbidity and mortality. THERAPEUTIC OPTIONS: A number of therapeutic options (tight blood sugar control, blood pressure reduction, lipid lowering) lead to a reduction of albuminuria and an improvement in cardiovascular prognosis. This has particularly been described for renin-angiotensin-aldosterone system-(RAAS-)blocking agents. Their use is not only associated with a reduced risk of end-organ damage (heart failure, diabetic nephropathy, cerebrovascular events) but has been described to decrease mortality as well. RECOMMENDATION: A timely diagnosis, a consecutive cardiovascular diagnostic work-up and the subsequent use of RAAS-blocking agents is indicated in patients in whom albuminuria has been diagnosed.     

Microalbuminuria screening in patients with hypertension: recommendations for clinical practice

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.     

Microalbuminuria in hypertension

Microalbuminuria is a sensitive marker of early renal damage in essential hypertension as well as diabetes mellitus. Elevated urinary albumin excretion has positive correlations with other cardiovascular risk factors. Microalbuminuria has an independent value to predict cardiovascular disease in the patients with not only diabetes mellitus but also with essential hypertension and even in general population. The seventh report of the joint national committee on prevention, detection, evaluation and treatment of high blood pressure (JNC 7) has adopted microalbuminuria or estimated glomerular filtration rate < 60 ml/min as one of the major cardiovascular risk factors. It is an important future task whether decrease in urinary albumin excretion with treatment improves prognosis of individual patients.     

Rapid progression of albumin excretion is an independent predictor of cardiovascular mortality in patients with type 2 diabetes and microalbuminuria.

OBJECTIVE: In patients with type 2 diabetes, microalbuminuria is associated with an increase in predominantly cardiovascular mortality. Considerable interindividual variability in the rate of progression of microalbuminuria exists. The prognostic significance of rate of progression of microalbuminuria with regard to cardiovascular and renal clinical end points is, however, unknown. The purpose of this study was to determine the prognostic significance of rate of progression of microalbuminuria for cardiovascular end points and renal function. RESEARCH DESIGN AND METHODS: In a previous prospective cohort study, progression of microalbuminuria (expressed as mean yearly change in albumin-to-creatinine ratio) was assessed in 58 patients with type 2 diabetes. During a median follow-up of 7 years after progression of microalbuminuria was determined, we registered all-cause mortality and coronary heart disease mortality as primary end points and coronary heart disease (fatal or nonfatal), peripheral vascular disease, ischemic stroke, retinopathy, macroalbuminuria, and change in serum creatinine as secondary end points. RESULTS: Seven subjects died during the study; five of these subjects died of coronary heart disease. Cox's regression analysis identified progression of microalbuminuria as a significant predictor of all-cause mortality (hazard ratio 1.46 per point increase in albumin-to-creatinine ratio per year, P < 0.001), coronary heart disease mortality (hazard ratio 2.32, P = 0.006), and macroalbuminuria (hazard ratio 1.79, P < 0.001). Adjustment for multiple cardiovascular risk factors did not affect these results. Identical analyses for baseline level of microalbuminuria instead of progression rate of microalbuminuria did not show significant hazard ratios. In addition, progression of microalbuminuria significantly predicted an increase in serum creatinine (r = 0.29, P = 0.04). CONCLUSIONS: In patients with type 2 diabetes and microalbuminuria, the rate of progression of albumin excretion seems to be a powerful independent predictor of mortality caused mainly by coronary heart disease.     

Importance of low-grade albuminuria

The well-described association between chronic kidney disease and cardiovascular disease is typically thought to originate from loss of renal function, as estimated by the glomerular filtration rate. However, recent data suggest that urinary albumin excretion has an important role in this association. Albuminuria is a marker of underlying vascular dysfunction and has been correlated with structural and functional integrity of the vasculature. Although the traditional upper limit of normal daily albumin excretion has been 30 mg/d, recent epidemiologic data suggest that levels in the general population are actually much lower. Further, within this range of low-grade albuminuria (LGA), increasing excretion rates are associated with increasing risk of cardiovascular disease. This association is independent of renal function, and in the earliest stages of chronic kidney disease, LGA seems to be a more important determinant than the glomerular filtration rate. This emerging association underscores the complexity of albumin excretion, in which subtle changes in albumin excretion reflect widespread vascular processes. Using the key words albuminuria, low-grade albuminuria, and microalbuminuria in a PubMed search of literature from January 1, 1995, to February 29, 2008, this review summarizes the most recent data on LGA and its association with cardiovascular and renal disease.     

Etiology and prognostic significance of albuminuria in diabetes

Persistent clinical proteinuria (i.e., urinary protein excretion greater than 0.5 g/24 h) is an ominous development in a person with diabetes. It eventually leads to a decline in the glomerular filtration rate and ultimately to end-stage renal failure or premature cardiovascular mortality. Progression of renal disease appears to be related to arterial blood pressure and protein intake and is primarily independent of the metabolic state. More sensitive immunoassays for detecting low concentrations of albumin in urine have led to recognition of subclinical increases in albumin excretion rates in nonclinically proteinuric diabetic patients, a phenomenon named microalbuminuria. Studies have shown that patients with microalbuminuria have a significantly increased risk for clinical proteinuria and cardiovascular mortality. Microalbuminuria is rarely found during the first 5 yr of a patient's diabetes, suggesting that it is a sign of early glomerular damage rather than a marker for susceptibility to it. In patients with non-insulin-dependent diabetes mellitus (NIDDM), an association has been found between microalbuminuria and coronary heart disease, but this relationship needs further investigation. In patients with insulin-dependent diabetes mellitus (IDDM), this subclinical form of proteinuria is associated with poor metabolic control and, more important, with marginal elevation of blood pressure. Correction of hyperglycemia by intensified insulin treatment might arrest progression to persistent clinical proteinuria; moreover, restricted protein intake and lowering of blood pressure have been shown to reduce the albumin excretion rate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prospective evaluation of urinary N-acetyl-beta-D-glucosaminidase with respect to macrovascular disease in elderly type 2 diabetic patients.

OBJECTIVE: To analyze prospectively the importance of urinary N-acetyl-beta-D-glucosaminidase (NAG), a marker for renal tubular function, in comparison with urinary albumin excretion (UAE), a marker for glomerular renal function, with respect to macrovascular disease in elderly patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We followed 124 patients over a mean period of 7.0 +/- 0.5 years. At baseline, urinary NAG, UAE, age, diabetes duration, sex, blood pressure, lipids, and serum creatinine were determined. Also, history of myocardial infarction (MI), stroke, severe peripheral vascular disease (PVD), antidiabetic and concomitant medication, and smoking habits were recorded. After 7 years, patients were reevaluated, and a multivariate logistic regression analysis was used to test risk factors for significance in order to predict macrovascular disease. Subgroups of patients were analyzed with respect to severe macrovascular disease, with a separate analysis for surviving patients. RESULTS: Compared with known cardiovascular risk factors such as microalbuminuria and total cholesterol, urinary NAG was similarly associated with cardiovascular disease for the total cohort (P < 0.05). Analyzing the subgroup of 65 patients still alive after follow-up care, urinary NAG and UAE were significantly elevated at baseline and at the time of follow-up care in patients with MI and PVD, but not in those with stroke (P < 0.01). There was a positive predictive trend of NAG excretion for the development of MI and PVD in our patients (P = 0.07). CONCLUSIONS: Urinary NAG proved comparable to UAE when analyzed with respect to preexistence and development of severe macrovascular disease. It needs to be determined by further studies if urinary NAG will be of value to serve as an adjunct marker to UAE in type 2 diabetic patients.     

Low plasma concentrations of diet-derived antioxidants in association with microalbuminuria in Indigenous Australian populations

Microalbuminuria is a risk factor for renal and cardiovascular diseases. Oxidant stress may contribute to vascular disease risk by promoting damage to renal and vascular tissues. This study examined the associations of plasma levels of diet-derived antioxidants with albuminuria in Australian population groups at high risk of renal and cardiovascular disease. Data on microalbuminuria and diet-derived plasma antioxidants were drawn from results of cross-sectional community-based risk factor surveys of Aboriginal and Torres Strait Islander peoples (n =698, 15 years and older). Prevalence of microalbuminuria ranged from 17-21%. After adjustment for age, gender, body mass index, diabetes, smoking status, plasma lipids and blood pressure, microalbuminuria was associated with significantly lower plasma concentrations of lycopene (-29%; P <0.001), beta-carotene (-22%; P <0.001), alpha-carotene (-22%; P <0.001) and cryptoxanthin (-17%; P <0.001) compared with normalbuminuric persons. Significant associations of microalbuminuria with plasma concentrations of alpha-tocopherol, retinol, lutein plus zeaxanthin and homocysteine were absent. The data are consistent with a protective effect of diets rich in carotenoids on vascular endothelium and/or renal tissues, and support the need for interventions to address affordable food supplies and dietary quality among Indigenous Australians.     

Vascular endothelial markers, von Willebrand factor and thrombomodulin index, are specifically elevated in type 2 diabetic patients with nephropathy: comparison of primary renal disease

To elucidate the hypothesis that albuminuria in diabetic subjects reflects widespread vascular damage, plasma markers for vascular endothelial damage was measured in diabetic subjects with various degrees of albuminuria and compared to results in patients with primary renal disease. The groups consisted of 31 non-diabetic patient controls with normoalbuminuria, 109 type 2 diabetic patients with normo- micro- and macro-albuminuria, and 16 proteinuric patients with primary renal disease. Endothelial markers, plasma von Willebrand factor (vWF) and thrombomodulin (TM), were measured by enzyme-linked immunosolvent assay and enzyme immunoassay (EIA) methods, respectively. Plasma vWF levels were similar in controls (119+/-7%, mean+/-S.E.M.) and diabetic patients with normoalbuminuria (139+/-6), but significantly elevated in diabetic patients with microalbuminuria (174+/-11) and macroalbuminuria (204+/-17), while the level was not increased in patients with primary renal disease (124+/-11). Because plasma TM level was strongly affected by kidney function, TM index (TM (FU/ml)/serum creatinine (mg %)) was used as an endothelial marker. The TM index was substantially increased in diabetic patients with overt nephropathy compared with controls (5.29+/-2.98 vs. 2.35+/-0.85), whereas this was not observed in patients with primary renal disease (3.25+/-0.29). Both vWF and TM index were significantly higher in diabetic patients with retinopathy than in the patients without retinopathy. These results suggest that generalized vascular endothelial damage occurs in diabetic nephropathy including the microalbuminuric stage, which is not attributed to kidney damage per se.     

糖尿病患者肾功能与糖尿病骨质疏松的关系

目的探讨糖尿病肾病与骨质疏松的关系.设计病例观察实验.单位四川大学华西医院内分泌科.对象依据1997年美国糖尿病协会诊断标准(空腹血糖≥7 mmol/L,餐后血糖≥11.1 mmol/L),选择入院96例糖尿病患者,男性56例,年龄＜60岁,女性40例,均未绝经,排除年龄的影响和因绝经导致的骨质疏松症,患者平均年龄为(48.7±10.5)岁,病程为1个月～21年不等,平均(7.85±2.56)年,所有患者一般情况差异无显著性.方法将纳入患者依据微量白蛋白排泄率及肾功能分成正常白蛋白尿组48例,微量白蛋白尿组28例,大量白蛋白尿组15例及肾功能衰竭组5例.采用双能X线仪测定96例患者的腰椎2～4节、股骨颈、沃德(氏)三角、转子的骨质密度,将有骨质疏松和无骨质疏松的患者分成2组对空腹血糖、餐后2 h血糖、糖基血红蛋白、碱性磷酸酶、钙、磷、血尿素氮、肌酐、体质量指数尿微量白蛋白排泄率等指标进行比较.主要观察指标所有糖尿病患者空腹血糖、餐后2 h血糖、糖基血红蛋白、碱性磷酸酶、钙、磷、血尿素氮、肌酐、体质量指数尿微量白蛋白排泄率;所有患者的骨密度.结果大量白蛋白尿组患者腰椎骨(L2～3)的骨密度与微量白蛋白尿组患者相比差异有显著性(P＜0.05),肾功能衰竭组患者髋关节及腰椎骨的骨密度与其他各组相比下降幅度较大,差异有显著性(P＜0.01).合并骨质疏松与未合并骨质疏松组间的病程、糖基血红蛋白、碱性磷酸酶、体质量指数差异有显著性(P＜0.05).结论随着肾脏损害加重骨质疏松发生率增高,糖尿病肾脏损害早期可能与骨密度下降和骨质疏松的发生密切相关.     

Therapeutic strategies for endothelial dysfunction

INTRODUCTION: A functionally compromised vascular endothelium is associated with tissue-damaging responses including inflammation, immune stimulation, oxidative stress and platelet activation/aggregation and can lead to severe end-organ damage, as implicated in the pathology of several cardiac, cerebral and renal disorders. Multiple noninvasive techniques are available for assessing endothelial dysfunction in clinical settings. Diverse interventions have been identified as having therapeutic potential for treating endothelial dysfunction and preventing its pathophysiological sequellae. AREAS COVERED: Evaluation techniques and interventional treatment approaches for endothelial dysfunction, with particular reference to prevalent cardiovascular and metabolic disorders such as coronary artery disease and diabetes. Limitations of the current treatments and avenues for improved endothelium-targeted therapies. EXPERT OPINION: Beneficial pleiotropic effects of various agents (cardiovascular medicines, antioxidants, nutritional supplements) on vascular endothelial function in humans notwithstanding, a growing body of preclinical data suggests that protein-, cell- and gene-based approaches hold promise for selective therapeutic targeting of the dysfunctional vascular endothelium. Additional efficacy data in appropriate animal models of vascular injury and cardiometabolic disease, further refinement of delivery modalities and continued investigation of the mechanisms underlying endothelial repair and regeneration should help identify the most promising therapeutic approaches for improving endothelial function that merit evaluation in human trials.     

The role of red blood cell distribution width in cardiovascular and thrombotic disorders

The red blood cell (RBC) distribution width (RDW) is a measurement of the size variation as well as an index of the heterogeneity of the erythrocytes (i.e., anysocytosis), which is typically used in combination with the mean corpuscular volume to troubleshoot the cause of an underlying anemia. Reliable data emerged from a variety of clinical studies have, however, disclosed a new and unpredictable scenario in the clinical usefulness of this measure, supporting the hypothesis that RDW might be a useful parameter for gathering meaningful clinical information, either diagnostic or prognostic, on a variety of cardiovascular and thrombotic disorders. Highly significant associations have been described between RDW value and all-cause, non-cardiac and cardiac mortality in patients with coronary artery disease, acute and chronic heart failure, peripheral artery disease, stroke, pulmonary embolism and pulmonary arterial hypertension. It is however still unclear whether anysocytosis might be the cause, or a simple epiphenomenon of an underlying disease, such as inflammation, impaired renal function, undernutrition, oxidative damage, or perhaps an element of both. Nevertheless, RDW is an easy, inexpensive, routinely reported test, whose assessment might allow the acquisition of significant diagnostic and prognostic information in patients with cardiovascular and thrombotic disorders.     

高尿酸血症与相关机体损伤研究进展

高尿酸血症是长期嘌呤代谢障碍致尿酸生成增多及（或）尿酸排泄减少所致的一种代谢性疾病。近年来,其发病率呈逐年上升趋势,发病年龄呈低龄化,这一情况引起了人们的关注。通过从分子水平及基因水平对高尿酸血症形成机制进行研究,经动物实验、临床研究以及体外细胞培养实验发现高尿酸血症与高血压、心血管、代谢综合征以及肾脏疾病等关系密切,被认为是导致这些疾病的危险因素。特别是高尿酸血症对肾脏的损伤,既往认为其损伤机理主要是尿酸结晶引起的梗阻及局部炎症反应,对无症状高尿酸血症不予以干预。现发现高尿酸血症可以激活肾素一血管紧张素一醛固酮（rennin—angioten—sin—aldoste—rone—system,RAAS）、启动炎症反应、引起血管内皮细胞损伤、血管平滑肌增殖等,是引起、加重甚至是预测肾脏损伤的因素,促使人们对其。肾损伤机理制的进一步探讨。     

Microalbuminuria in treated hypertensives: only a mirror image of cardiovascular risk? The HUNT Study, Norway

OBJECTIVES: Microalbuminuria as an independent marker of cardiovascular morbidity and mortality in hypertensive individuals is under debate. The aim of this study was to study the possible associations between microalbuminuria on one hand and known cardiovascular risk factors and cardiovascular disease on the other hand, in a large, unselected population of treated hypertensives without diabetes. DESIGN: Cross-sectional study. SETTING: Participants of the HUNT Study, Norway (n = 65,258). SUBJECTS: 5,369 individuals (> or =20 years) with treated hypertension delivered three morning urine samples for microalbuminuria analysis. MAIN OUTCOME MEASURES: Microalbuminuria expressed as albumin-to-creatinine ratio, cardiovascular risk factors and cardiovascular disease. RESULTS: Increasing age, pulse pressure (systolic blood pressure-diastolic blood pressure), s-creatinine, cigarette pack years, cardiovascular disease, antihypertensive medication group, and years with antihypertensive medication were significantly associated with microalbuminuria in men. Increasing pulse pressure, cigarette pack years, and antihypertensive medication group were associated with microalbuminuria in women, adjusted for other cardiovascular risk factors. When excluding individuals of both sexes with self-reported cardiovascular disease and blood pressure > 160/90 mm Hg, no variable associated with cardiovascular risk factors registered was statistically associated with microalbuminuria. CONCLUSION: The present study indicates that microalbuminuria mainly represents a mirror image of hypertension (BP > 160/90) and prior or present cardiovascular disease. We therefore question whether the treatment quality would improve if yet another risk factor, microalbuminuria, were introduced as a routine test in treated hypertensives.     

Dealing with diabetic nephropathy

Nephropathy may develop in patients with type 1 diabetes because poor glycemic control produces effects that eventually lead to glomerular scarring and renal failure. The worse and more prolonged the hyperglycemia, the greater the risk of diabetic nephropathy. In patients with type 2 diabetes, hyperglycemia, as well as insulin resistance and generalized vascular disease, is involved in the pathogenesis of nephropathy. The glomerular changes of early diabetic nephropathy can be identified only by renal biopsy or by testing for microalbuminuria. Once macroalbuminuria occurs (albumin excretion rate, > 300 mg/day), usually after type 1 diabetes has been present for 10 to 15 postpubertal years, end-stage renal disease is almost inevitable. However, aggressive control of hypertension in diabetic patients without microalbuminuria helps avoid nephropathy, and tight glycemic control in those with microalbuminuria can avoid or delay its onset. Even when macroalbuminuria is present, treatment can prolong renal function. Aggressive antihypertensive therapy, especially with ACE inhibitors, can reduce renal decline by half. Avoiding circumstances that may damage the kidneys (e.g., use of radiocontrast materials or nephrotoxic drugs, dehydration, hyperlipidemia, urinary tract infection, buildup of AGEs) is critical. Some treatment methods are controversial (dietary protein restriction) or still under investigation (use of injected or oral heparin) but may help delay renal transplantation or dialysis.     

Asymmetric dimethylarginine (ADMA): the silent transition from an 'uraemic toxin' to a global cardiovascular risk molecule

Endothelial dysfunction as a result of reduced bioavailability of nitric oxide (NO) plays a central role in the process of atherosclerotic vascular disease. In endothelial cells NO is synthesized from the amino acid l-arginine by the action of the NO synthase (NOS), which can be blocked by endogenous inhibitors such as asymmetric dimethylarginine (ADMA). Acute systemic administration of ADMA to healthy subjects significantly reduces NO generation, and causes an increase in systemic vascular resistance and blood pressure. Increased plasma ADMA levels as a result of reduced renal excretion have been associated with atherosclerotic complications in patients with terminal renal failure. However, a significant relationship between ADMA and traditional cardiovascular risk factors such as advanced age, high blood pressure and serum LDL-cholesterol, has been documented even in individuals without manifest renal dysfunction. As a consequence, the metabolism of ADMA by the enzyme dimethylarginine dimethylaminohydrolase (DDAH) has come into the focus of cardiovascular research. It has been proposed that dysregulation of DDAH with consecutive increase in plasma ADMA concentration and chronic NOS inhibition is a common pathophysiological pathway in numerous clinical conditions. Thus, ADMA has emerged as a potential mediator of atherosclerotic complications in patients with coronary heart disease, peripheral vascular disease, stroke, etc., being the culprit and not only an innocent biochemical marker of the atherosclerotic disease process.     

糖尿病患者尿液中白蛋白尿指标检验研究

目的：研究糖尿病患者尿液中白蛋白尿指标对于疾病的反映程度.方法：选取2011年8月至2013年12月泰安市某中医院临床确诊的男性2型糖尿病患者,所有患者符合2007年美国糖尿病学会（ADA）制订的《糖尿病临床实用指南》中糖尿病诊断标准.依据尿蛋白水平分为3组,研究白蛋白尿指标的变化.结果：本研究发现,各组患者的尿液代谢产物水平呈现完全不同的分布.其中,尿白蛋白正常组可能包括单纯DN（糖尿病肾病）以及Mogensen（糖尿病肾病疾病）分期中Ⅰ期和Ⅱ期DN患者.结论：据此发现疾病早期诊断和进展的候选标志物.进一步证实尿白蛋白正常组并非一个均一整体,部分尿白蛋白正常患者与微量白蛋白尿患者代谢水平差异不大,可能已存在肾脏损伤.     

Microalbuminuria associated with diabetic neuropathy.

OBJECTIVE--To test the hypothesis that microalbuminuria may show an independent statistical association with diabetic neuropathy. RESEARCH DESIGN AND METHODS--An observational study of a prospectively identified cohort was conducted at the University Medical Center. The cohort consisted of 78 consecutive diabetic patients who fulfilled the criteria of having diabetes for greater than 10 yr, a normal serum creatinine, urine negative for macroalbuminuria by a commonly used dipstick method, a blood glucose less than 13.8 mM (less than 250 mg/dl), and an HbA1 less than 11% (normal range 5.5-8.5%). Medical record review established the presence of chronic complications of diabetes. Urine albumin level was measured by radioimmunoassay. Albumin concn greater than or equal to 15 mg/L was used as a cutoff value for microalbuminuria. RESULTS--Twenty-five of 78 patients (32%) showed microalbuminuria. Of these, 51% had neuropathy, 39% had retinopathy, 35% arterial hypertension, 17% peripheral vascular disease, and 15% ischemic heart disease. After adjusting for age, sex, and type and duration of diabetes, diabetic neuropathy and hypertension showed a significant association with microalbuminuria. After adjusting for other diabetic complications, diabetic neuropathy showed a significant association with microalbuminuria. CONCLUSIONS--Microalbuminuria is independently associated with diabetic neuropathy. This association lends support to the theory of a vascular etiology for diabetic distal symmetrical neuropathy.