The validity of screening based on spot morning urine samples to detect subjects with microalbuminuria in the general population

BACKGROUND: No study has yet investigated the validity of prescreening by albumin measurements in a spot morning urine sample to identify in the general population subjects with microalbuminuria. We therefore tested the diagnostic performance of urinary albumin concentration (UAC) and albumin-creatinine ratio (ACR), measured in a spot morning urine sample, in predicting a urinary albumin excretion (UAE) > or =30 mg in subsequent 24-hour urines (microalbuminuria). METHODS: Subjects (2527) participating in the PREVEND study, a representative sample from the general population, collected a spot morning urine sample and, on average, 77 days later, two 24-hour urine collections. RESULTS: The ROC curve of UAC in predicting microalbuminuria has an area-under-the-curve of 0.92 with a discriminator value of 11.2 mg/L. Using this cut-off value for UAC, sensitivity in predicting microalbuminuria is 85.0%, and specificity 85.0%. For ACR these values are, respectively: area-under-the-curve 0.93, discriminator value 9.9 mg/g, sensitivity 87.6%, and specificity 87.5%. Sensitivity for UAC in predicting microalbuminuria does not differ significantly from the sensitivity for ACR, whereas the difference between the specificities of UAC and ACR reaches statistical significance, but is numerically very small. In various subgroups characterized by differences in urinary creatinine excretion, the area-under-the-ROC curve, sensitivity, as well as specificity, do not increase relevantly compared to the results in the overall study population. This holds true for ACR as well as UAC. CONCLUSION: The diagnostic performance of measuring UAC in a spot morning urine sample in predicting microalbuminuria in subsequent 24-hour urine collections is satisfactory, and, moreover, comparable to that of measuring ACR. In order to keep the burden and costs involved in population screening for microalbuminuria as low as possible, we therefore propose prescreening by measuring UAC in a spot morning urine sample. Those subjects with a UAC above a certain predefined level (e.g., 11 mg/L) should be asked to collect timed urine samples.     

Genome-wide linkage analysis to urinary microalbuminuria in a community-based sample: the Framingham Heart Study

INTRODUCTION: Microalbuminuria is a powerful risk factor for cardiovascular disease. It is not known whether genetic factors play a role in the expression of microalbuminuria in population-based samples. METHODS: Genome-wide variance components linkage-analysis using 401 markers spaced at approximately 10 cM was performed on subjects from 330 extended families of the Framingham Heart Study; a subanalysis was performed on families enriched for hypertension. Urinary microalbumin was indexed to urinary creatinine [urine albumin/creatinine ratio (UACR)] and was log-transformed for analysis. Residuals of log-transformed UACR adjusted for age, gender, body mass index, diabetes, systolic blood pressure, hypertension treatment, smoking, and serum creatinine were used in the linkage analysis. RESULTS: Among 1055 subjects (52% women), mean age 56 years, median UACR was 5.8 mg/g (11% >30 mg/g). The unadjusted heritability for UACR was 0.20; after multivariable adjustment, heritability was 0.16. The peak multivariable-adjusted multipoint logarithm of odds (LOD) score was 2.22 on chromosome 8 at 135 cM (marker D8S1179); one LOD support interval = 129 - 145 cM. In the subanalysis in families enriched for hypertension (N= 676), the peak multivariable-adjusted LOD score of 2.11 was observed at the same location. CONCLUSION: We found suggestive linkage to urinary microalbumin on chromosome 8. At least one potential candidate gene implicated in the pathogenesis of nephropathy (HAS2) lies in this region. Further research is warranted to understand the genetic basis of microalbuminuria.     

Effect of glycemic control on microalbuminuria development among type 2 diabetes with high-normal albuminuria

This study was aimed at revealing the factors and the interrelationships between factors on microalbuminuria development among type 2 diabetes (T2D) patients. Between 2004 and 2011, 461 T2D patients with a baseline urine albumin-to-creatinine ratio (UACR) of <30?mg/g, and an estimated glomerular filtration rate (eGFR) of >60?mL/min were evaluated retrospectively. Sixty-eight (14.8%) subjects had developed microalbuminuria in a mean follow-up of 6.82 years. Statistical analysis had revealed that the higher baseline UACR (10?mg/g; sensitivity, 80.9%, specificity, 63.6%; AUC?=?0.774) and glycohemoglobin level (HbA1c) (8%; sensitivity, 72.1%, specificity, 61.6%; AUC?=?0.698) were the two independent microalbuminuria risk factors. When considering the risk of microalbuminuria, the data were normalized with respect to subjects with low-normal UACR (<10?mg/g) and HbA1c??8%, high-normal UACR/HbA1c?8% were 2.59 (p?=?0.107), 6.15 (p?=?0.001), and 16.96 (p?10%) showed a progressively increase of the hazard risk in baseline high-normal UACR group. But the same correlation was not shown in the low-normal UACR group. This study identified the relationships of high-normal albuminuria and glycemic control on microalbuminuria development among T2D patients. Glycemic control is especially beneficial for T2D patients with baseline high-normal UACR in preventing microalbuminuria development.     

First Morning Voids Are More Reliable Than Spot Urine Samples to Assess Microalbuminuria

Measurement of urinary albumin excretion (UAE) in a 24-h collection is the gold standard method to determine the presence of microalbuminuria. We sought to compare more practical alternatives—measurement of urinary albumin concentration (UAC) or albumin:creatinine ratio (ACR)—in a first morning void or in a spot urine sample with this gold standard. We asked 241 participants of a prospective cohort study to make three 24-h urine collections, a first morning void, and a spot urine sample. Regression analysis showed that the ACR in a first morning void best agreed with 24-h UAE. The prevalence of microalbuminuria determined by data from a first morning void (7.5%, whether by UAC or ACR) nearly equaled the prevalence of microalbuminuria determined by 24-h UAE (10.0%), whereas the prevalence was higher when determined by spot urine samples (25.4% for UAC and 22.4% for ACR; both P < 0.001 versus 24-h UAE). The intraindividual coefficients of variation of the ACR in a first morning void and 24-h UAE were similar (19%). Intraindividual coefficients of variations of all other measurements of albuminuria were significantly greater. In conclusion, measurement of albuminuria in a first morning void, preferably as the ACR, is more reliable than a spot urine sample to diagnose and monitor microalbuminuria.Microalbuminuria has been established as a valuable risk marker for renal and cardiovascular complications. Consequently, treatment guidelines from various medical societies have recommended assessment of urinary albumin in patients with hypertension or diabetes and even in the general population to identify individuals at increased risk for renal and cardiovascular disease.^1–4Various methods for urine collection are used in clinical practice to determine presence of microalbuminuria. Because urinary albumin excretion (UAE) follows a circadian rhythm, the amount of albumin excreted in urine during a 24-h period has been considered the “gold standard”; however, 24-h urine collection is a cumbersome procedure. More practical and easier alternatives are collection of a first morning void or a spot (random) urine sample. It has been suggested that a first morning void (collection of the first urine void after the individual awakes from sleep) is to be preferred over a spot urine sample (daytime random sample), because the former is less influenced by factors such as hydration status and physical activity, reducing the variability that is caused by these factors.⁵ From a practical point of view, however, spot urine samples are preferred because they can be collected during consultation at the doctor''s office and therefore pose the least inconvenience for individuals.As yet, only one study has compared the validity of using a first morning void or a spot urine sample as a substitute for a 24-h urine collection to diagnose microalbuminuria and to monitor albuminuria over time⁶; however, this study included only 11 patients, limiting the validity of the results. The aim of this study, therefore, was to investigate whether albuminuria measures derived from a first morning void or a spot urine sample could be used as an alternative to a 24-h UAE to diagnose microalbuminuria and to monitor albuminuria over time.     

Relationship between antinuclear antibody and microalbuminuria in the general population: the Takahata study

BACKGROUND: Microalbuminuria, a marker of vascular damage, is associated with increased risk of progressive renal deterioration, cardiovascular disease and mortality. However, the relationship between antinuclear antibody (ANA) and microalbuminuria in the general population is unknown. Thus, we conducted a cross-sectional study to examine the relationship between ANA and microalbuminuria. METHODS: The subjects of this community-based study were individuals over 40 years old in Takahata, Japan. The urine albumin-creatinine ratio (UACR) was calculated from a single-spot urine specimen collected in the morning. ANA was examined by enzyme immunoassay (EIA). RESULTS: Among the 2,875 subjects (mean age 63 years; men 1,276; women 1,599), positive ANA (ANA index >or=20.0) was detected in 16.9% of the total population (men 12.9%, women 20.3%) and the prevalence of positive ANA increased with age. The prevalence of microalbuminuria (UACR 30-300 mg/g), but not macroalbuminuria (UACR > 300 mg/g), was significantly higher in the positive ANA group than the negative ANA group (24.1% vs. 16.0%, respectively, P < 0.001). Along with the increase of the ANA index, the prevalence of microalbuminuria and UACR levels were increased. Multivariate logistic regression analyses showed that ANA was significantly associated with microalbuminuria (odds ratio [OR] 1.63 and 95% confidence interval [95%CI] 1.27-2.10). These associations were significant in women, but not men, when examined separately. CONCLUSIONS: These results indicate that the presence of ANA is associated with microalbuminuria in the general population, especially women.     

Cross-sectional relations of serum aldosterone and urine sodium excretion to urinary albumin excretion in a community-based sample

Experimental models suggest that increased aldosterone and sodium intake are associated with renovascular damage and resultant proteinuria. We hypothesized that serum aldosterone and urinary sodium would be associated with urinary albumin excretion, an indicator of kidney damage. We evaluated 2700 participants (53% women, mean age 58 years) from the Framingham Offspring Study who attended a routine examination between 1995 and 1998, who were free of heart failure and renal failure, and underwent testing for serum aldosterone, spot urinary sodium, and urinary albumin excretion (urine albumin/creatinine ratio, UACR), the latter two indexed to urinary creatinine. Stepwise multivariable linear regression was used to evaluate the relations between UACR with urinary sodium index and serum aldosterone. In multivariable regression, log urinary sodium index was associated positively with log-UACR (P<0.0001). UACR levels in the fourth and fifth quintiles of urinary sodium index were 24% (95% confidence interval (CI) 3-49%), and twofold higher (95% CI 72-150%), respectively, relative to the lowest quintile (P-value for trend across quintiles <0.001). In multivariable models, log-transformed aldosterone was not related to log-UACR. The top quintile of serum aldosterone levels was associated with a 21% higher (95% 1-44%) UACR levels relative to the lowest quintile. Urinary albumin excretion was strongly and positively associated in a continuous fashion with urinary sodium excretion, whereas a weaker nonlinear positive relation with serum aldosterone was noted. Our cross-sectional observations raise the possibility that dietary salt intake may be associated with early renovascular damage.     

Non-albuminuric renal disease among subjects with advanced stages of chronic kidney failure related to type 2 diabetes mellitus

Urinary albumin excretion has been consistently found to be normal in a significant number of subjects with early stages of diabetic kidney disease. This study was aimed to estimate the prevalence and characteristics of non-albuminuric chronic kidney disease associated with type 2 diabetes mellitus among subjects who reach advanced stages of renal failure. Study population was composed of incident patients with advanced chronic kidney disease (glomerular filtration rate <30?mL/min) related to type 2 diabetes in a tertiary hospital from Gran Canaria (Spain) during a period of 2 years. Subjects were classified as normoalbuminuric (urinary albumin-to-creatine ratio [UACR] <30?mg/g), microalbuminuric (UACR ≥30 and <300?mg/g), or proteinuric (UACR ≥300?mg/g). Of 78 eligible patients, 21.8% had normoalbuminuria, 20.5% had microalbuminuria, and 57.7% had proteinuria. Individuals with normoalbuminuria were mostly women and had a lower prevalence of smoking and polyneuropathy than subjects with microalbuminuria or proteinuria. They also presented greater measures of body mass index and waist circumference, higher values of total and LDL cholesterol, and lower values of HbA_1c and serum creatinine than subjects with microalbuminuria or proteinuria. Multivariate analysis demonstrated that female sex (positively) and HbA_1c and polyneuropathy (negatively) were independently associated with absence of albuminuria. In conclusion, around 20% of subjects with diabetes-related advanced chronic kidney disease, characteristically women, have normal urinary albumin excretion. HbA_1c and polyneuropathy are inversely related to this non-albuminuric form of nephropathy.     

Clinical characteristics of normotensive renal transplant recipients with microalbuminuria and effects of angiotensin II type I receptor antagonist on urinary albumin excretion

AIM: Microalbuminuria is typically observed in renal transplant recipients with systemic hypertension. The effects of angiotensin II type 1 receptor antagonist (losartan) on the hypertensive recipients have been evaluated. However, the clinical background of normotensive recipients with microalbuminuria and the effect of losartan administration in those subjects have not been clarified. One of the two purposes for the present study was to investigate the clinical characteristics of normotensive recipients with microalbuminuria. The other was to evaluate the effect of losartan on urinary excretion of albumin in these patients. METHODS: The clinical data and the change of the single kidney glomerular filtration rate (GFR) for the graft by radionuclide study were assessed in 13 normotensive recipients with microalbuminuria. These were compared with the data of 13 normotensive patients without microalbuminuria. The 13 recipients with microalbuminuria were treated with losartan for one year and urine excretion of albumin, N-acetyl-beta-D-glucosaminidase (NAG) and serum creatinine (S-Cr) levels were measured. RESULTS: The GFR of the grafts from donors to recipients significantly increased (30.9 to 55.2 mL/min) in microalbuminuric recipients, but did not significantly increase in the non-microalbuminuric recipients. Decreases of the urinary excretion rate of albumin (351 +/- 261 at baseline to 158 +/- 14 mg/gCr at 12 months), NAG (13 +/- 5 to 10 +/- 3 IU/gCr) and S-Cr (1.7 +/- 0.6 to 1.5 +/- 0.4 mg/DL) were observed in the microalbuminuric recipients with losartan administration. CONCLUSIONS: The present study suggests that an increased single kidney GFR of the graft from the donor in situ to the recipient might be a cause of microalbuminuria in normotensive recipients. The one-year effects of losartan were observed in terms of the decrease in urinary excretion of albumin, NAG and S-Cr levels.     

Estimated glomerular filtration rate and urinary albumin excretion are independently associated with greater arterial stiffness: the Hoorn Study

Mild renal insufficiency is a risk factor for cardiovascular disease (CVD). Both a decline in GFR and (micro)albuminuria are associated with greater cardiovascular mortality. In ESRD, arterial stiffness, an important cause of CVD, is known to be greater, but few data exist in individuals with mild renal insufficiency or microalbuminuria. This study investigated the association of impaired renal function expressed as lower GFR or greater urinary albumin excretion with arterial stiffness. In a population-based study in 806 individuals (402 men), mean age 68 yr (range 50 to 87), peripheral arterial stiffness (by compliance and distensibility of the carotid, brachial, and femoral arteries and by the carotid elastic modulus [E(inc)]) and central arterial stiffness (by total systemic arterial compliance, carotid-femoral transit time, and aortic augmentation index) were measured ultrasonically. GFR was estimated (eGFR) by the Modification of Diet in Renal Disease (MDRD) formula. Urinary albumin excretion was expressed as urinary albumin/creatinine ratio (UACR). eGFR was 60.6 +/- 11.1 ml/min per 1.73 m(2). Median UACR was 0.57 mg/mmol (range 0.1 to 26.6). After adjustment for age, mean arterial pressure (MAP), gender, and glucose tolerance status (GTS), each 5-ml/min per 1.73 m(2) lower eGFR was associated with a lower distensibility coefficient of the carotid (regression coefficient beta -0.20 10(-3)/kPa; 95% confidence interval [CI] -0.34 to -0.07 10(-3)/kPa) and brachial artery (-0.15 10(-3)/kPa; 95% CI -0.28 to -0.03 10(-3)/kPa) and a greater carotid E(inc) (0.02 kPa; 95% CI 0.0004 to 0.04 kPa). No statistically significant association was found of eGFR with other arterial stiffness indices. After adjustment for age, MAP, gender, and GTS, a greater UACR (per quartile) was associated with a greater E(inc) (0.03 kPa; 95% CI 0.001 to 0.07 kPa) and a trend to a lower distensibility coefficient (-0.24 10(-3)/kPa; 95% CI -0.49 to 0.02 10(-3)/kPa) of the carotid artery. After adjustment for age, MAP, gender, and GTS, a greater UACR (per quartile) was in addition associated with a shorter carotid-femoral transit time (-1.67 ms; 95% CI -3.24 to -0.10 ms). These associations were not substantially changed by mutual adjustment for eGFR and UACR. In individuals with mild renal insufficiency, both a lower eGFR and a greater albumin excretion, even below levels that are considered to reflect microalbuminuria, are independently associated with greater arterial stiffness. Moreover, these associations were mutually independent. These findings may explain, in part, why eGFR and microalbuminuria are associated with greater risk for CVD and suggest that amelioration of arterial stiffness could be a target of intervention.     

Clinical utility of trace proteinuria for microalbuminuria screening in the general population

Background The urine dipstick test that regards > 1+ proteinuria as positive is unsuitable for microalbuminuria screening owing to its low sensitivity in the general population. We conducted a cross-sectional survey to examine whether trace proteinuria could be an indicator of microalbuminuria. Methods The subjects were 2321 participants in a community-based health check-up in Takahata, Japan. Dipstick tests for proteinuria and the urine albumin–creatinine ratio (UACR) measurement were performed with single-spot urine specimens collected early in the morning. The results of the dipstick tests were recorded as (−), trace, (1+), (2+), and (3+). Micro- and macroalbuminuria were defined as UACR 30–300 mg/g and > 300 mg/g, respectively. Results Overall, the prevalence and median UACR levels of urine protein (−), trace, (1+), (2+), and (3+) were 92.0% (8.8 mg/g), 3.5% (43 mg/g), 2.6% (81 mg/g), 1.4% (315 mg/g), and 0.5% (1073 mg/g), respectively. Within the trace proteinuria category, the prevalence of microalbuminuria in all subjects, men, subjects ≥60 years, diabetic subjects, and hypertensive subjects was 59.3%, 73.8%, 71.2%, 88.9%, and 68.0%, respectively. By regarding trace proteinuria as positive, the sensitivity of the urine protein dipstick test for micro- and macroalbuminuria was improved (from 23.3% to 37.1%), while its specificity was not significantly changed (from 98.9% to 97.3%). Conclusion Trace proteinuria could be a useful indicator of microalbuminuria in the general population, and especially in subjects at high risk of cardiovascular disease.     

The predictive value of the product of contrast medium volume and urinary albumin/creatinine ratio in contrast-induced acute kidney injury

Preexisting renal impairment and the amount of contrast media are the most important risk factors for contrast-induced acute kidney injury (CI-AKI). We aimed to investigate whether the product of contrast medium volume and urinary albumin/creatinine ratio (CMV?×?UACR) would be a better predictor of CI-AKI in patients undergoing nonemergency coronary interventions. This was a prospective single-center observational study, and 912 consecutive patients who were exposed to contrast media during coronary interventions were investigated prospectively. CI-AKI is defined as a 44.2?μmol/L rise in serum creatinine or a 25% increase, assessed within 48?h after administration of contrast media in the absence of other causes. Fifty patients (5.48%) developed CI-AKI. The urinary albumin/creatinine ratio (UACR) (OR?=?1.002, 95% CI?=?1.000–1.003, p?=?.012) and contrast medium volume (CMV) (OR?=?1.008, 95% CI?=?1.001–1.014, p?=?.017) were independent risk factors for the development of CI-AKI. The area under the ROC curve of CMV, UACR and CMV?×?UACR were 0.662 (95% CI?=?0.584–0.741, p?p?p?相似文献   

人体测量学肥胖指标与微量白蛋白尿的相关性研究

目的 探讨人体测量学肥胖指标与微量白蛋白尿(microalbuminuria,MAU)的相关性.方法 在青岛市城阳区人民医院2012年流行病学调查数据库中收集调查人群1170例,留取清晨随机尿测定尿微量白蛋白(urinary albumin,UAlb)和尿肌酐(urinary creatine,UCr),计算比值(urinary albumin creatine rate,UACR)并根据UACR水平分为:正常白蛋白尿组(nornal albumin urine,NAU)(807例)和MAU组(363例),收集人体测量学指标和测定生化指标,作统计学处理.结果 ①与NAU组相比,MAU组年龄、空腹血糖(fasting blood glucose,FBG)、舒张压(diastolic blood pressure,DBP)、收缩压(systolic blood pressure,SBP)、血清尿酸(serun urinary acid,SUA)、腰围(waist circumference,WC)、腰身比(Waist to height ratio,WTHR)、腰臀比(Waist to hip ratio,WHR)均高于前者,差异有统计学意义(P＜0.05或P＜0.01);与NAU组相比,MAU 组高血糖(hyperglycemia,HG)、原发性高血压(primary hypertension,PHT)、血脂异常(dyslipidemia,DLP)及OB,尤其腹型肥胖(abdominal obesity,AOB)患病率升高,差异有统计学意义(P＜0.05或P＜0.01);②多元线性回归分析显示,对MAU贡献大小依次WTHR＞ WC＞ WHR;③采用受试者工作特征曲线(ROC)分析男性人群WTHR、WHR、WC等预测MAU的曲线下面积依次为0.68(95％CI:0.67 ～ 0.70)、0.64(95％ CI:0.62 ～0.65)、0.57 (95％ CI:0.55～0.59),预测切点0.52、0.90、91.8 cm.在女性人群中,WSR、WC、WHR等预测MAU的曲线下面积依次为0.71(95％CI:0.70～0.72)、0.69 (95％ CI:0.68～0.70)和0.64(95％ CI:O.62 ～0.65),预测切点0.52、0.84、82.5 cm.结论 ①AOB为MAU的高危人群;②WTHR为最佳预测指标,切点为0.52,其次为WC和WHR,男性切点分别为89.6 cm和0.88 cm,女性为84.5 cm和0.84 cm.     

Urinary albumin and insulin as predictors of coronary artery disease: An angiographic study.

Microalbuminuria has been associated with cardiovascular risk factors, events, and mortality. It also clusters with hyperinsulinemia and the metabolic syndrome. How urinary albumin excretion and the fasting serum insulin level relate to coronary artery disease (CAD) has not been previously determined. In 308 patients undergoing elective coronary angiography, the albumin to creatinine ratio was measured in urine from an early morning void. The fasting serum insulin level was also determined. CAD was assessed by angiography. Urinary albumin excretion was 28 +/- 5 mg/g (mean +/- SE) in patients with CAD and 10 +/- 1 mg/g in those without CAD (P < 0.001). Fasting serum insulin levels were also greater in patients with CAD compared with those without CAD; 20 +/- 3 and 13 +/- 1 microU/mL, respectively (P = 0.016). Urinary albumin excretion and fasting serum insulin levels increased progressively with severity of CAD. In patients without diabetes (n = 255), significant relationships of urinary albumin excretion and the fasting serum insulin levels to CAD were observed, but they were more pronounced when patients with diabetes (n = 53) were included. In multiple regression analysis, the odds ratios for severe CAD were 2.2 (95% confidence interval, 1.1 to 4.5) for microalbuminuria and 2. 2 (95% confidence interval, 1.3 to 3.8) for hyperinsulinemia. In summary, urinary albumin excretion and the fasting serum insulin levels were directly related to angiographic evidence of CAD. Microalbuminuria and hyperinsulinemia predict a significantly elevated risk for coronary atherosclerosis.     

Inflammation and microalbuminuria in nondiabetic and type 2 diabetic subjects: The Insulin Resistance Atherosclerosis Study

BACKGROUND: Microalbuminuria is a risk factor for cardiovascular disease, but the underlying pathomechanisms are still poorly understood. A relationship between C-reactive protein (CRP), a sensitive marker of inflammation, and atherosclerotic disease has been reported recently. METHODS: We hypothesized that microalbuminuria might be associated with chronic inflammation and investigated the relationship of urinary albumin excretion, as assessed from the albumin-to-creatinine ratio (ACR), in an untimed morning urine specimen, and two inflammatory markers (CRP and fibrinogen) in the large, triethnic population of the Insulin Resistance Atherosclerosis Study (IRAS). After exclusion of subjects with macroalbuminuria, 1481 subjects were studied. RESULTS: Both inflammatory markers were related to urinary ACR (r = 0.17 for CRP and r = 0.14 for fibrinogen, both P = 0.0001), an association that remained significant after adjustment for demographic variables, diabetic status, smoking, and use of angiotensin-converting enzyme inhibitors (P < 0.01). Mean levels of CRP and fibrinogen were elevated in microalbuminuric (N = 262) versus normoalbuminuric (N = 1219) subjects (5.37 +/- 0.47 vs. 3.80 +/- 0.15 mg/L and 295.7 +/- 4. 0 vs. 278.2 +/- 1.6 mg/dL, both P < 0.0001). The associations were consistent among nondiabetic and type 2 diabetic subjects and among the three ethnic groups of the IRAS (non-Hispanic whites, blacks, Hispanics). In a logistic regression model, fibrinogen was independently associated with microalbuminuria (P = 0.047), along with hypertension, female gender, waist circumference, and fasting blood glucose, while CRP was not independently related to microalbuminuria in this model (P = 0.26). CONCLUSION: We have shown an association of CRP and fibrinogen with urinary albumin excretion in the microalbuminuric range in type 2 diabetic and nondiabetic individuals. Chronic inflammation therefore emerges as a potential mediator between microalbuminuria and macrovascular disease.     

Retinopathy is independently related to microalbuminuria in type 2 diabetes mellitus.

AIM, SUBJECTS AND METHODS: To evaluate whether microalbuminuria is related to retinopathy in type 2 diabetes, we studied a sample of 125 known diabetic subjects with a mean disease duration of 11 years (range 5-22 years), aged 46-71 years, by ophthalmoscopy, fundus photography and fluoresceine angiography. Urinary albumin excretion rate (UAER) was measured by nephelometry and the fractional clearance of albumin, i.e. in relation to creatinine was calculated from spot samples. The subjects were classified into groups based on the UAER/24 h. RESULTS: Microalbuminuria was present if UAER was 30-300 mg/24 h and overt nephropathy when UAER > or = 300 mg/24 h. Background (> or = 2 microaneurysms or > or = 2 hemorrhages or > or = 1 more advanced lesions, except proliferative changes) and proliferative retinopathies were found in 21% and in 3%, respectively. Subjects with microalbuminuria (p = 0.026) and overt nephropathy (p = 0.002) had more frequently background retinopathy than their counterparts with a normal UAER (chi2-test). A multivariate logistic regression model was obtained for background retinopathy (chi2 = 37.5, p = 0.0000039, OR 14.9, correct prediction of negative outcome in 97% and of positive outcome in 30.4%) including the following variables. The fractional clearance of albumin independently explained background retinopathy (OR 3.9, 95% CI 1.3-12, p = 0.028). Insulin therapy (p = 0.0017), diabetes duration (p = 0.048), blood glucose at 2 h in standard oral glucose tolerance test (p = 0.009) and low fasting serum HDL cholesterol (p = 0.023) also independently explained retinopathy. Age, gender, BMI, systolic blood pressure, ACE inhibitor therapy, fasting serum total cholesterol and triglyceride, blood glucose or insulin, hemoglobin A1c, glucagon-stimulated C peptide response, glomerular filtration rate or smoking habits did not independently explain retinopathy. CONCLUSION: We conclude that microalbuminuria is related to background retinopathy in type 2 diabetes.     

Relationship between urinary albumin excretion and glomerular filtration rate in normotensive, nonproteinuric patients with type 2 diabetes mellitus

BACKGROUND/AIM: In patients with type 2 diabetes mellitus, the relationship between glomerular filtration rate (GFR) and urinary albumin excretion remains an unresolved issue. In order to investigate the early renal function abnormalities, GFR and urinary albumin excretion were assessed, and their relationship was examined in normotensive patients with type 2 diabetes mellitus. METHODS: In a cross-sectional study of 85 nonhypertensive Japanese patients with type 2 diabetes mellitus not showing overt proteinuria, the GFR was measured using (99m)Tc-diethylenetriamine pentaacetate renography. Fifty-one diabetic patients lacked microalbuminuria (albumin excretion <30 mg/day), while 34 patients showed microalbuminuria (between 30 and 300 mg/day). Fifteen healthy subjects served as controls. RESULTS: The three groups were well matched with regard to gender, age, and body mass index. The GFR in microalbuminuric patients (134 +/- 23 ml/min/1.48 m(2)) was significantly higher than in patients without microalbuminuria (108 +/- 21 ml/min/1.48 m(2)) and in controls (109 +/- 18 ml/min/1.48 m(2); p < 0.0001). In type 2 diabetic patients, the GFR positively correlated with the logarithmically transformed urinary albumin excretion. Multiple regression analysis showed that the urinary albumin excretion was significantly and independently affected by GFR (beta = 0.548), duration of diabetes (beta = 0.297), and systolic blood pressure (beta = 0.232; R(2) = 0.409; p < 0.0001). CONCLUSION: It is suggested that one of the mechanisms underlying increased urinary albumin excretion in early nephropathy in normotensive type 2 diabetes is glomerular hyperfiltration.     

Serum ionized magnesium levels in type 2 diabetic patients with microalbuminuria or clinical proteinuria

BACKGROUND/AIMS: The association between microalbuminuria and magnesium depletion is a controversial issue, and serum ionized magnesium levels have not been previously studied in patients with different grades of diabetic nephropathy. Therefore, the aim of this study was to evaluate circulating ionized magnesium concentrations in patients with non-insulin-dependent diabetes mellitus (NIDDM) and incipient or overt diabetic nephropathy. METHODS: We measured fasting plasma glucose, creatinine, creatinine clearance estimate, total cholesterol and triglycerides, and serum ionized magnesium (ion-selective electrodes, ISE) in 30 NIDDM patients with urinary albumin excretion rate (UAER) <20 microg/min (normoalbuminuria), 30 NIDDM patients with microalbuminuria (20 < UAER < 200 microg/min), 30 NIDDM patients with clinical proteinuria (UAER >200 microg/min), and 20 healthy subjects. RESULTS: Serum ionized magnesium levels were significantly reduced in diabetic patients when compared to control subjects (0.39 +/- 0.06 vs. 0.58 +/- 0.05 mmol/l, p < 0.001). Moreover, diabetic patients with microalbuminuria or clinical proteinuria showed a significant decrease in serum ionized magnesium with respect to normoalbuminuria group (normoalbuminuria: 0.45 +/- 0. 02 mmol/l; microalbuminuria: 0.36 +/- 0.05 mmol/l, p < 0.001; clinical proteinuria: 0.35 +/- 0.04 mmol/l, p < 0.001). Serum ionized magnesium showed a significant negative correlation with plasma HbA1c and triglycerides in both microalbuminuria and clinical proteinuria groups. Multiple linear regression analysis showed that circulating ionized magnesium levels decrease together with the increase of plasma HbA1c and triglycerides in NIDDM patients with incipient or overt nephropathy, also after adjusting for age, sex, BMI, diabetes duration, systolic and diastolic blood pressure, hypoglycemic therapy, plasma creatinine, creatinine clearance, plasma cholesterol and fasting glucose. CONCLUSIONS: Microalbuminuria and clinical proteinuria, as well as poor glycometabolic control and hypertriglyceridemia, are associated to relevant alterations in magnesium metabolism, and the measurement of serum ionized magnesium seems to represent a useful biochemical tool for the study of magnesium disturbances in patients with different grades of diabetic nephropathy.     

尿胞外体1型辅助性T细胞/2型辅助性T细胞失衡与2型糖尿病肾病的相关性

目的 探讨2型糖尿病（DM）患者尿胞外体1型辅助性T细胞/2型辅助性T细胞（Th1/Th2）的变化与2型糖尿病肾病（DN）发生发展的相关性。 方法 选取120例2型糖尿病患者及健康对照组30例为对象,根据尿白蛋白肌酐比（UACR）,2型糖尿病患者分为糖尿病非肾病组（DM,40例,UACR<30 mg/gCr）、微量白蛋白尿组（DN1,50例,UACR≥30~300 mg/gCr）和临床白蛋白尿组（DN2,30例,UACR＞300 mg/gCr）。用特异性单克隆抗体提纯尿胞外体。用酶联免疫吸附法（ELISA）检测尿胞外体干扰素γ（IFN-γ）和白细胞介素4（IL-4）水平。用多元逐步回归方法分析尿胞外体IFN-γ/IL-4比值与糖化血红蛋白（HbA1c）、胆固醇（CH）、UACR、血肌酐（Scr）、尿素氮（BUN）相关性。 结果 DM、DN1、DN2组胞外体Th1/Th2水平显著高于健康对照组（0.8089±0.2458、0.8993±0.3515、0.8571±0.2470比 0.6198±0.1769,均P < 0.01）。DN1组胞外体Th1/Th2显著高于DM组（P < 0.01）。尿胞外体IFN-γ/IL-4与UACR（r = 0.213,P = 0.015）、BUN（r=0.292,P = 0.001）呈正相关。逐步多元回归分析显示, BUN是尿胞外体IFN-γ/IL-4的独立影响因素（β = 0.246,P = 0.006）。 结论 尿胞外体Th1/Th2漂移与2型糖尿病肾病密切相关,可能在糖尿病早期肾病发病过程中起重要的作用。     

Urinary albumin excretion rate during angiotensin II infusion in microalbuminuric patients with insulin and non-insulin-dependent diabetes mellitus

As angiotensin-converting enzyme inhibition is accompanied by a marked decrease in glomerular protein loss, the hypothesis was tested that an increase of the glomerular transcapillary hydraulic pressure difference by exogenous angiotensin II would increase microalbuminuria in patients with insulin (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM). Acute effects of increasing doses of angiotensin II (1, 3 and 6 ng/kg/min) were studied on mean arterial pressure (MAP), glomerular filtration rate (GFR); effective renal plasma flow (ERPF), filtration fraction (FF), total renal vascuclar resistance (TRVR), and urinary albumin excretion rate (UAER) in 11 IDDM and 11 NIDDM microalbuminuric patients. Angiotensin II infusion changed MAP from 100±3 mmHg at baseline to 105±3, 111±3, and 116±3 mmHg (P <0.001), ERPF from 542±29 to 478±24, 429±23, and 382±19 ml/min (P <0.001), FF from 20.2±0.06 to 23.1±0.07, 27.1±1.1, and 29.8±1.2% (P <0.001), and TRVR from 9454±809 to 11 158±930, 13 310±1206, and 15 538±1362 dyne s cm^-5 (P <0.001). GFR and UAER, however, did not change significantly. Therefore, during angiotensin II infusion ERPF decreased, while FF and TRVR increased. As UAER and GFR remained unchanged, the presumed rise in intraglomerular capillary pressure by exogenous angiotensin II did not increase UAER. We suggest that during manipulation of the renin-angiotensin system, as in other renal diseases with proteinuria, factors other than glomerular transcapillary hydraulic pressure determine the degree of urinary albumin loss in microalbuminuric IDDM and NIDDM patients.     

Microalbuminuria as a possible marker of risk of Balkan endemic nephropathy

Aim: To evaluate whether microalbuminuria could be a marker of early tubular damage in individuals at risk of developing Balkan endemic nephropathy (BEN). Methods: A cross-sectional study was used to determine urinary albumin-to-creatinine ratio (UACR) in a test group of 61 participants from a BEN endemic region and control group of 64 participants from a nearby non-endemic region, both recruited from the general population of Bosnia and Herzegovina. The correlation between UACR and urinary b2 microglobulin-to-creatinine ratio (UBCR) and the receiver operating characteristic curve for UACR were analyzed in the test groups of 58 participants. The correlation analysis was also performed in a subset of nine subjects with elevated UBCR. Results: Medians, interquartile ranges and confidence intervals (CI) for medians of UACR in the test and control groups were 2 mg/mmol, 0.975–8.247 mg/mmol, 1.3472–3.2691 mg/mmol and 1 mg/mmol, 0.695–1.41 mg/mmol, 0.8466–1.2053 mg/mmol, respectively (P = 0.0001). Microalbuminuria was found in 30 of the 61 examinees in the test group, in contrast to six of the 64 examinees in the controls (P < 0.0001). Participants from the endemic region had 9.3 times the odds of having microalbuminuria in contrast to participants from the non-endemic region. Pearson's correlation coefficients r of the log-transformed ratios and Kendall–tau coefficients of rank correlation in the group of 58 and in a subset of nine subjects with elevated UBCR were: 0.55 (P < 0.0001); 0.317 (P = 0.0005) and 0.59 (P = 0.045); 0.48 (P = 0.037), respectively. The area under the curve for UACR was 0.882 (P = 0.0001), sensitivity 100% and specificity 67.3%. Conclusion: Microalbuminuria may be a useful marker of early tubular injury in individuals at risk of developing BEN.