Association of monocyte chemoattractant protein-1 with renal tubular damage in diabetic nephropathy

Monocyte chemoattractant protein-1 (MCP-1), is a chemokine that mediates renal interstitial inflammation, tubular atrophy, and interstitial fibrosis by recruiting monocytes/macrophages into renal tubulointerstitium. Recent studies have demonstrated that protein overload in renal tubular cells up-regulates MCP-1 gene and its protein expression. Therefore, we hypothesized that increased expression of MCP-1 in renal tubuli, probably triggered by an increase in the leakage of plasma protein from glomerular capillary to tubular fluid, may contribute to renal tubular damage and accelerate the progression of diabetic nephropathy. To test this hypothesis, we examined urinary excretion levels of MCP-1 and N-acetylglucosaminidase (NAG), a sensitive marker of renal tubular damage, in Japanese Type II diabetic patients with normoalbuminuria (n=29), microalbuminuria (n=25), and macroalbuminuria (n=18). The median urinary excretion level of MCP-1 in patients with macroalbuminuria (394.4 ng/g creatinine) was significantly elevated compared to the levels in patients with normoalbuminuria and microalbuminuria (159.6 and 193.9 ng/g creatinine, respectively). Furthermore, the urinary MCP-1 excretion level was positively correlated with urinary excretion levels of albumin (r=.816, P<.001) and NAG (r=.569, P<.001) in all subjects. These results suggest that MCP-1 is produced in renal tubular cells and released into urine in proportion to the degree of proteinuria (albuminuria), and that increased MCP-1 expression in renal tubuli contributes to renal tubular damage. Therefore, we conclude that heavy proteinuria itself may accelerate the progression of diabetic nephropathy by increasing the MCP-1 expression in renal tubuli.     

The meaning of serum levels of advanced glycosylation end products in diabetic nephropathy

It has been reported that advanced glycosylation end products (AGEs) play an important role in the development of diabetic complications. To evaluate the relationship between serum AGEs and diabetic nephropathy, we measured serum AGE levels in diabetic patients with normoalbuminuria (N), microalbuminuria (M), overt proteinuria (O), and hemodialysis (HD), non diabetic patients with nephropathy, and age-matched control subjects using the enzyme-linked immunosorbent assay (ELISA). Urine AGE levels were also measured in these subjects except group HD. Serum AGE levels in diabetic patients were not significantly higher than those in the normal subjects. When we compared serum AGE levels among various stages of diabetic nephropathy, groups O and HD had significantly higher serum AGE levels than the other groups. Serum AGE levels in group HD were almost 6-fold higher than those in groups N and M. In contrast, there were no significant differences in urinary AGE levels among any diabetic groups. As for the variables that determine serum AGE levels in diabetic patients, there was no significant correlation between serum AGEs and fasting blood glucose, hemoglobin A1c (HbA1c), or duration of diabetes. In contrast, serum AGEs showed a strong correlation with serum creatinine and an inverse correlation with creatinine clearance. To evaluate the relationship between serum AGEs and oxidative stress in diabetic nephropathy, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and serum malondialdehyde (MDA), which are biological markers of total oxidative stress in vivo, were also examined. Both urinary 8-OHdG and serum MDA levels were significantly higher in diabetic patients with proteinuria versus those without proteinuria. However, there was no significant correlation between serum AGEs and urinary 8-OHdG or serum MDA levels in diabetic patients. These results suggest that the accumulation of serum AGEs in diabetic nephropathy may be mainly due to decreased removal in the kidney rather than increased production by high glucose levels or oxidative stress.     

Prevalence of micro- and macroalbuminuria,arterial hypertension,retinopathy and large vessel disease in European Type 2 (non-insulin-dependent) diabetic patients

Summary The prevalence of micro- and macroalbuminuria was determined in Type 2 (non-insulin-dependent) diabetic patients, less than 76 years of age, attending a diabetic clinic during 1987. All eligible patients (n=557) were asked to collect a 24-h urine sample for quantitative albumin analysis. Urine collections were obtained in 296 males and 253 females (96%). Normoalbuminuria were defined as urinary albumin excretion30 mg/24 h (n=323), microalbuminuria as 31–299 mg/24 h (n=151), and macroalbuminuria as 300 mg/ 24 h (n=75). The prevalence of macroalbuminuria was significantly higher in males (20%) than in females (6%), while the prevalence of microalbuminuria was almost identical in males (26%) and females (29%). The prevalence of arterial hypertension increased with increased albuminuria, being 48%, 68%, and 85% in patients with normoalbuminuria, microalbuminuria, and macroalbuminuria respectively. Prevalence of proliferative retinopathy rose with increasing albuminuria, being 2%, 5% and 12% in patients with normoalbuminuria, microalbuminuria, and macroalbuminuria respectively. Prevalence of coronary heart disease, based on Minnesota coded electrocardiograms, was more frequent in patients with macroalbuminuria (46%) compared to patients with microalbuminuria (26%) and patients with normoalbuminuria (22%). Foot ulcers were more frequent in micro- and macroalbuminuric patients, being 13% and 25%, respectively, compared to 5% in patients with normoalbuminuria. This cross-sectional study has revealed a high prevalence of microalbuminuria (27%) and macroalbuminuria (14%) in Type 2 diabetic patients. Patients with raised urinary albumin excretion are characterized by obesity, elevated haemoglobin A_lc, increased frequency of arterial hypertension, proliferative retinopathy, coronary heart disease and foot ulcers. Thus, these findings suggest that urinary excretion of albumin should be monitored routinely in patients with Type 2 diabetes.     

N(carboxymethyl)lysine as a biomarker for microvascular complications in type 2 diabetic patients

AIMS: Hyperglycemia is linked to vascular dysfunction in patients with diabetes mellitus, either directly or through advanced glycation end product (AGE) formation. Experimental evidence has indicated the possible involvement of AGEs in the genesis of vascular complications. We investigated whether serum levels of AGEs and of the glycoxidation compound carboxymethyl-lysine (CML) were increased and correlated with vascular complications in type II diabetes mellitus. METHODS: Serum levels of AGEs and CML-human serum protein (CML-HSP) were measured by a specific immunoassay in 51 men and 26 women aged 58 +/- 6.1 years (mean +/- SD) who had been treated for type II diabetes mellitus for 11 +/- 8 years, and in a non-diabetic control group consisting of 39 men and 21 women aged 55.5 +/- 7.5 years. Patients with macroalbuminuria or abnormal creatinine clearance were excluded from the study. RESULTS: The serum levels of AGEs were significantly increased in patients with type II diabetes compared to controls (P<0.001). Blood levels of CML-HSP were significantly increased in diabetic patients compared to normal subjects [35.3 +/- 27.4 and 9.3 +/- 7.2 (mean +/- SD) pmol/mg of protein, respectively; P<0.0001]. In diabetic patients with retinopathy or microalbuminuria (urinary albumin excretion: UAE > 30 mg/24 h), CML-HSP levels were significantly higher (P<0.02), and even more elevated in patients with both complications. CONCLUSION: In patients with type II diabetes, CML-HSP levels that are at variance with the HbA(1c) index for blood glucose may be a biomarker of glycoxidation, and related to the development of microvascular complications.     

URINARY EXCRETION OF HUMAN EPIDERMAL GROWTH FACTOR IN THE VARIOUS STAGES OF DIABETIC NEPHROPATHY

Epidermal growth factor (EGF) is a polypeptide mitogen first isolated from mouse submaxillary glands and later from human urine. We have examined the pattern of urinary excretion of human EGF (hEGF) in normal subjects and in diabetic patients with varying degrees of nephropathy. hEGF was measured by homologous radioimmunoassay and expressed in terms of urinary creatinine excretion. On the basis of their albumin excretion rate, the diabetic patients were divided into those with normoalbuminuria (albumin excretion rate 3.5 (1.4-9.8) micrograms/min; mean (range)), microalbuminuria (albumin excretion rate 75 (30-128) micrograms/min) and macroalbuminuria (289 (169-879) micrograms/min). The albumin excretion rate for the normal subjects was 3.7 (1.6-9.7) micrograms/min. The mean (range) hEGF excretion (nmol hEGF/mmol creatinine) was 0.69 (0.47-1.29) for 19 healthy subjects, 0.60 (0.16-1.36) for the normoalbuminuric group (n = 18; NS), 0.47 (0.10-0.83) for the microalbuminuric patients (n = 19; P less than 0.001 vs controls and normoalbuminuric diabetics) and 0.38 (0.10-0.63) for the macroalbuminuric group (n = 18; P less than 0.001 vs controls and normoalbuminuric diabetics). There was an inverse correlation between albumin excretion rate and hEGF: creatinine ratio (r = -0.49; P = 0.02). These results show a progressive decline in hEGF excretion in diabetic patients with varying degrees of nephropathy and do not support the hypothesis that increased kidney size seen in early nephropathy is due to excessive amounts of EGF in the urine.     

The protein–creatinine ratio in spot morning urine samples and 24-h urinary protein excretion in patients with systemic lupus erythematosus

A 24-h urinary protein is a standard way to diagnose lupus nephritis. Assessment of protein–creatinine (Pr–Cr) ratio in morning spot urine is a valuable method in diabetic patients but not use in systemic lupus erythematous (SLE) patients routinely. In this study Pr–Cr ratio in spot urine was compare with 24-h urine protein; if they have valuable correlation we can use this test instead of 24-h urinary protein. The aim of this study was to evaluate the correlation of spot urine Pr–Cr ratio for prediction of significant proteinuria (≥300 mg/24 h) in patients with SLE. A cross-section study was conducted in 74 hospitalized women with SLE. The correlation between Pr–Cr in first morning urine specimens and urinary protein excretion in 24-h collections were analyzed. Correlation between Pr–Cr ratio in spot morning urine specimens and urinary protein excretion in 24-h collections was significant (P < 0.0001, r = 0.83). A high correlation and precision of agreement were demonstrated between the two methods of assessment proteinuria in lupus patients. The difference between the two methods was less than the biological variability in the protein excretion and its measurement, enabling the methods to be used interchangeably creatinine ratio in spot morning urine samples is a precise indicator of proteinuria in patients with lupus nephritis and represents a simple and inexpensive procedure in establishing severity of proteinuria in patients with SLE.     

Plasma concentrations of VCAM-1 and ICAM-1 are elevated in patients with Type 1 diabetes mellitus with microalbuminuria and overt nephropathy.

AIMS: Elevated urinary albumin excretion is associated with macrovascular atherosclerotic complications in Type 1 diabetes mellitus. Adhesion molecules mediate leucocyte adhesion to the endothelium early in the atherosclerotic process. The present study tests the hypothesis that microalbuminuria and diabetic nephropathy are associated with elevated plasma concentrations of soluble vascular adhesion molecule (sVCAM)-1, soluble intercellular adhesion molecule (sICAM)-1, and soluble E-selectin (sE-selectin) aiming to illustrate factors of potential pathogenetic relevance for the excess cardiovascular disease in diabetic patients with renal complications. METHODS: Soluble adhesion molecule concentrations were measured by enzyme-linked immunosorbent assays (ELISA) in healthy controls (n = 16) and in 59 Type 1 diabetic patients: group 1-patients with normoalbuminuria (n = 16); group 2-patients with microalbuminuria (n = 15); group 3-patients with macroalbuminuria and normal serum creatinine (n = 15), group 4-patients with macroalbuminuria and moderately elevated serum creatinine (n = 13). RESULTS: Plasma concentrations of sVCAM-1 and sICAM-1 were similar in healthy controls and normoalbuminuric Type 1 diabetic patients, but the concentrations were increased by the presence of microalbuminuria and overt nephropathy (P < 0.001 and P < 0.0001, ANOVA). Concentrations of sE-selectin did not differ between diabetic patients and controls. CONCLUSIONS: Plasma concentration of sICAM-1 is elevated in Type 1 diabetic patients with microalbuminuria and the concentrations of sICAM-1 as well as sVCAM-1 are elevated in patients with macroalbuminuria and normal s-creatinine. The elevated plasma concentrations of these soluble adhesion molecule concentrations in patients with renal complication can be of pathogenetic importance for the development of atherosclerosis and plasma soluble adhesion molecule concentrations may provide additional information on cardiovascular risk.     

糖尿病患者尿液中期因子与糖尿病肾病的关系

目的探讨尿液中期因子（MK）与糖尿病肾病的关系。方法96例糖尿病患者,根据尿白蛋白排泄率分为正常白蛋白尿组（NUAlb组）,微量白蛋白尿组（MUAlb组）,大量白蛋白尿组（CUAlb组）,设对照组（NC组）。用酶联免疫吸附法测定尿液MK水平。结果CUAlb组尿液MK水平高于NC组、NUAlb组及MuAlb组（P〈0．01）,MUAlb组高于NC组及NUAlb组（P〈0．05）,NUAlb组与NC组差异无统计学意义（P〉O．05）。相关分析显示,尿液MK与尿白蛋白排泄率（r=0．40,P〈O．05）及病程（r=0．23,P〈0．05）呈正相关,与内生肌酐清除率（CCr）呈负相关（r=-0．20,P=〈0．05）。结论尿液MK可能参与临床糖尿病肾病的发生。     

尿脂联素与糖尿病肾病严重程度的相关性研究

目的 探讨尿脂联素与糖尿病肾病严重程度的相关性.方法 150例糖尿病患者根据尿微量白蛋白/肌酐(ACR)分为正常白蛋白尿组(ACR＜ 30 mg/g),微量白蛋白尿组(ACR30～300 mg/g),大量白蛋白尿组(ACR＞ 300 mg/g),每组均为50例.同时选取健康体检者30名作为对照组.应用全自动生化分析仪测定空腹血糖、HbA1c、肌酐、白蛋白、甘油三酯、总胆固醇、高密度脂蛋白-胆固醇(HDL-C)、低密度脂蛋白-胆固醇(LDH-C)等生化指标.采用酶联免疫吸附法测定血、尿脂联素水平.结果 血、尿脂联素及HbA1c水平在对照组、正常白蛋白尿组、微量白蛋白尿组及大量白蛋白尿组中依次升高,差异均有统计学意义(F=62.46,65.26,5.37,P均＜0.05);血肌酐水平随尿白蛋白水平升高依次升高,微量白蛋白尿组及大量白蛋白尿组与对照组之间比较,差异有统计学意义(F=8.25,P＜0.05),微量白蛋白尿组及大量白蛋白尿组与正常白蛋白尿组之间比较无明显统计学意义(P＞0.05);估算的肾小球滤过率(eGFR)随尿白蛋白水平升高依次降低(F=54.67,P＜0.01).Pearson相关分析显示尿脂联素与血肌酐、ACR、血脂联素、HbA1c呈正相关(r=0.66,0.61,0.62,0.35,P均＜0.05),与eGFR呈负相关(r=-0.71,P＜0.01).多元逐步回归分析发现尿脂联素与血肌酐、HbA1c、ACR、eGFR及血脂联素相关(P均＜0.05).结论 尿脂联素与糖尿病肾病的严重程度呈正相关.     

Screening for proteinuria in a rheumatology clinic: comparison of dipstick testing, 24 hour urine quantitative protein, and protein/creatinine ratio in random urine samples.

Measurements of protein/creatinine ratio in 'spot' urine samples were compared with measurements of 24 hour quantitative proteinuria and side room 'dipstick' testing in 104 samples from 90 patients presenting consecutively to a rheumatology unit. Linear regression analysis showed a highly significant correlation between the random urinary protein/creatinine ratio and total protein excretion in 24 hour urine samples (r = 0.92, p less than 0.001, y = 6.55x + 0.04). Although an approximation of 24 hour urinary protein excretion could have been made from the regression line: 24 hour urine protein = 6.55 x protein/creatinine ratio + 0.04 (g/l), there was a wide scatter of values, particularly in patients with greater than 1 g/24 h urinary protein excretion. Nevertheless, significant proteinuria (greater than 300 mg/24 h) could have been confirmed or excluded with a sensitivity and specificity of 97% by adopting random protein/creatinine values of less than 0.04 as 'normal'. Specificity and sensitivity could have been increased to 100%, however, by excluding patients with values lying between 0.01 and 0.10 as all the false negatives (n = 3) and false positives (n = 3) lay within this range. In comparison, dipstick testing, although 100% sensitive, had a poor specificity due to the high false positive rate (40/83 (48%] in patients with 1+ to 3+ readings. Assessment of random urinary protein/creatinine ratio may obviate the need for 24 hour urine collections in the initial assessment of suspected proteinuria. A wider application of this technique seems indicated in view of the obvious advantages in terms of cost, time, and patient convenience.     

Screening of diabetic patients for microalbuminuria in primary care--The PROSIT-Project. Proteinuria Screening and Intervention.

The PROSIT (Proteinuria Screening and Intervention) Project started in 1993 in order to obtain data on the prevalence of micro- and macroalbuminuria in diabetic patients treated in primary care, to establish an easy screening programme for microalbuminuria, in which also diabetic patients can participate in self-responsibility, and to implement a specific intervention programme for incipient nephropathy. In 58 representative doctor's offices 647 diabetic patients were included, who performed at home self-tests for microalbuminuria on three days within one week using the early morning urine and a newly developed qualitative immunologic test-strip for microalbuminuria. After storage they returned the same urine samples to their doctors' offices for semiquantitative retesting with the immunologic test-strip Micral-Test II. In case of positive results the proteinuria dipstick Combur-9-Test was applied in order to exclude other causes of positive microalbuminuria (e.g. urinary tract infection). Data of 569 patients (6% Type 1, 88% Type 2 and 6% secondary diabetes) could be analysed. Both qualitative self-testing for microalbuminuria at home and semiquantitative retesting in doctors' offices were found to be feasible. Based on semiquantitative retesting the prevalences of microalbuminuria (macroalbuminuria) were 19.6% (0%) in Type 1 diabetes, 17.2% (10.8%) in Type 2 diabetes and 11.7% (7.8%) in secondary diabetes. Type 2 diabetic patients showed a clear correlation between albuminuria and diabetes duration, HbA1c, serum creatinine, triglycerides as well as micro- and macrovascular complications. 227 patients with micro- or macroalbuminuria were included into the ongoing PROSIT intervention programme.     

山莨菪碱与卡托普利对糖尿病肾病的影响

以放射免疫测定法检测尿白蛋白，筛选出糖尿病肾病４７例（其中早期４０例，临床期７例），随机分成两组，采用自身对照试验比较山莨菪碱与卡托普利对糖尿病肾病的影响。结果显示：山莨菪碱和卡托普利治疗４周后，患者有效肾血浆流量上升，肾小球滤过分数下降，而肌酐清除率无明显变化；尿白蛋白平均下降４９ｍｇ／ｄ（Ｐ＜０．０１）与５７ｍｇ／ｄ（Ｐ＜０．００５）：这表明山莨菪碱具有与卡托普利类似的降低尿蛋白和改善肾功能的作用。     

Plasma lipids and urinary albumin excretion rate in Type 1 diabetes mellitus: the EURODIAB IDDM Complications Study.

AIMS: To examine the relationship between increased urinary albumin excretion rate and fasting plasma lipids among male and female respondents to the EURODIAB IDDM Complications Study, and attempt to explain inconsistencies in previous reports. METHODS: A cross-sectional study of 3250 randomly selected Type 1 diabetic patients from 31 diabetes clinics in 16 European countries was carried out between 1989 and 1990. Plasma lipids and urinary albumin were measured centrally. The present analysis was confined to the subgroup of 2205 patients attending after a 10-12 h overnight fast. Mean age was 33 years (SD 10) and mean duration of Type 1 diabetes mellitus was 15 years (SD 9). RESULTS: The prevalence of microalbuminuria (24-h urinary albumin excretion rate 20-200 microg/min) was 21.7% (95% confidence interval 19.9-23.5) and macroalbuminuria (24-h urinary albumin excretion rate > 200 microg/min) 7.8% (6.6-9.0). In comparison to patients with normal urinary albumin excretion rate (< 20 microg/min), and after controlling for age, sex, glycaemic control, duration of diabetes and current smoking, macroalbuminuria was associated with significantly (P<0.01) increased fasting plasma triglycerides, cholesterol, LDL-cholesterol, cholesterol:HDL-cholesterol ratio and, in women, reduced HDL-cholesterol. In men and women with microalbuminuria, the only significant association was with increased plasma triglycerides. CONCLUSIONS: These data confirm that there is an association between fasting plasma lipids and increasing urinary albumin excretion rate in European Type 1 diabetic patients. In microalbuminuric patients, however, the association was weaker than previously reported and partly explained by confounding factors.     

环氧化酶2基因-765G／C多态性与昆明地区汉族2型糖尿病患者糖尿病肾病发生、发展的关系

目的 探讨环氧化酶2基因启动子区-765G/C多态性与昆明地区汉族2型糖尿病患者糖尿病肾病发生、发展的相关性.方法 选取2008年1月至12月昆明医学院第一附属医院糖尿病科收治住院的2型糖尿病患者252例,根据24 h尿白蛋白排泄率或随机尿白蛋白/肌酐比值分至无糖尿病肾病组（n=100）、隐性糖尿病肾病组（n=78）、显性糖尿病肾病组（n=74）.运用聚合酶链反应-限制性片段长度多态性方法检测环氧化酶2基因启动子区-765G/C多态性.检测血糖、血脂和其他生化指标.运用χ^2检验比较各组基因型频率和等位基因频率,运用方差分析比较各组相关临床及生化指标,采用logistic回归分析评价影响糖尿病肾病发生、发展的危险因素.结果 两糖尿病肾病组-765GG基因型频率与无糖尿病肾病组存在明显差异（0.901 vs 0.810;χ^2=4.309,P＜0.05）.糖尿病肾病患者中,-765GG基因型携带者空腹血糖、餐后2 h血糖与非携带者存在明显差异[分别为（7.9±4.0）vs（5.9±1.7）mmol/L,（12±5）vs（9±4）mmol/L;t值分别为0.001、0.020,均P＜0.05＝.logistic回归分析提示,-765GG基因型是糖尿病肾病发生的独立危险因素之一[比值比（OR）=3.25,95%可信区间（CI）为1.336～7.901].结论 在昆明地区汉族2型糖尿病患者中,环氧化酶2基因启动子区-765GG基因型与糖尿病肾病的发生、发展有关.     

Urinary N-acetyl-beta-D-glucosaminidase excretion in insulin-dependent diabetes mellitus: relation to microalbuminuria, retinopathy and glycaemic control

N-Acetyl-beta-D-glucosaminidase (NAG) excretion was measured in early morning urine samples from 133 Albustix-negative, normotensive insulin-dependent diabetic patients and 89 non-diabetic controls. Urinary NAG activity was determined using a chromogenic substrate, 2 methoxy-4-(2'-nitrovinyl)-phenyl 2-acetamido-3-deoxy-beta-D-glucopyranoside, and expressed as mumol MNP released/hour/mmol of creatinine. Overall, diabetic patients were found to have a significantly elevated mean urinary NAG activity (p less than 0.01) compared to controls. Within the diabetic patients urinary NAG activity was significantly elevated in patients with either microalbuminuria (p less than 0.001) or "poor" glycaemic control (p less than 0.001), but not in those with retinopathy (p = 0.117). Three-way analysis of variance revealed that the relationship of raised urinary NAG to microalbuminuria and "poor" glycaemic control were statistically independent. Elevated urinary NAG excretion in insulin-dependent diabetes mellitus appears to be associated with early diabetic nephropathy and poor long-term glycaemic control.     

Microalbuminuria in diabetes: a population study of the prevalence and an assessment of three screening tests

A single observer reviewed 842 of the 917 known diabetic patients registered with 40 GPs in the Poole area. A midstream urine specimen was tested for proteinuria using Albustix (Ames) and cultured to detect bacterial infection. After the first 3 months of the survey, the aliquot of this specimen was frozen for later determination of the random albumin/creatinine ratio (R-Alb/Creat). Patients were requested to submit a timed overnight urine collection for estimation of urinary albumin excretion rate (AER). Of the 842 patients reviewed, 493 (59%) submitted timed overnight urine collections; 43 were excluded because of urinary infection and/or proteinuria. One hundred and thirty-three (30%) of 450 diabetic patients were found to have microalbuminuria, although only 31 (7%) had an AER greater than 30 micrograms/min. Six hundred and seven urine samples were collected for R-Alb/Creat but 68 were excluded because of infection and/or proteinuria; in 10 further samples urinary creatinine was not measured. Two hundred and four (38%) of 532 diabetic patients were found to have an elevated R-Alb/Creat. There was a significant correlation between AER and R-Alb/Creat (r = 0.32, p less than 0.001) but a considerable number of patients showed either a normal AER and high R-Alb/Creat or the reverse. The value of R-Alb/Creat or an overnight urinary albumin concentration, or an overnight urinary albumin/creatinine ratio (ON-Alb/Creat) as screening tests to predict AER greater than 30 micrograms/min was assessed. An ON-Alb/Creat greater than 2.0 mg/mmol was the optimal screening test (sensitivity 96% and specificity 99.7%).(ABSTRACT TRUNCATED AT 250 WORDS)     

糖尿病肾病患者血清电解质水平变化的研究

目的 探讨糖尿病肾病(DN)患者血清电解质变化,及与尿微量白蛋白的相关性.方法 选取2013年4月至2014年10月在天津中医药大学第二附属医院内科住院的2型糖尿病患者450例,按尿微量白蛋白排泄率(UAER)结果分为3组,＜20 μg/min为无DN组(176例),20～200 μg/min为微量白蛋白尿组(182例),≥200 μg/min为大量白蛋白尿组(92例).同时检测患者血清电解质钾、钠、氯、磷、镁、钙水平,并留取患者一般资料,分析各种电解质变化与DN的关系.结果 3组间的钾、磷、钙、镁水平有差异,大量白蛋白尿组的钾(F=11.139,P＜0.01)、磷(F=3.115,P＜0.05)水平最高,镁(F=7.251,P＜0.05)、钙(F=5.721,P＜0.01)水平最低.微量白蛋白尿组与大量白蛋白尿组患者的钾、磷水平均高于无DN组,镁水平低于无DN组(P＜0.05或P＜0.01).大量白蛋白尿组钙水平低于无DN组(P＜0.01).与微量白蛋白尿组相比,大量白蛋白尿组钾、磷水平升高,而钙、镁水平降低(P＜0.05或P＜0.01).直线相关分析显示,磷、钾水平与24 h尿微量白蛋白呈正相关(r=0.348,0.258,P＜ 0.001).钙、镁水平与24h尿微量白蛋白呈负相关(r=-0.360,-0.374,P＜0.001).结论 DN患者随着尿微量白蛋白的增多,钾、磷水平逐渐升高,镁、钙水平逐渐降低.     

von Willebrand factor antigen in plasma and urine in patients with type I (insulin-dependent) diabetes mellitus with and without nephropathy.

von Willebrand factor (vWF) antigens were quantitatively and qualitatively analyzed in plasma and urine in 41 patients with type I (insulin-dependent) diabetes. The patients were divided into three groups according to their albumin excretion: group N (n = 24) without any excretion (less than 20 micrograms/min), group M (n = 8) with microalbuminuria (20-200 micrograms/min), and group P (n = 9) with persistent albuminuria (greater than 200 micrograms/min). Healthy subjects served as controls (n = 28). The plasma concentration of vWF was higher (p less than 0.05) in the patients with diabetes mellitus than in the controls. Differences between the groups of patients were not statistically significant. The typical multimeric structure described for vWF in normal plasma was observed in all patients. In urine, significantly higher excretion of vWF fragments was observed in the three diabetic study groups as compared with the controls. In group P the patients' urinary vWF/creatinine levels tended to be higher than in groups N and M. Qualitative analysis of urinary vWF fragments demonstrated a similar distribution pattern of fragments, with three distinctive peaks, in the patients of groups N and M and in the controls. The distribution pattern of vWF fragments in group P, however, differed clearly from that in the controls and showed a great variation within the group. The urinary fragments tended to be of a higher molecular weight and several less distinct fragments with the whole spectrum of molecular weight were observed. Because in these patients with proteinuria no qualitative changes appeared in plasma, it is suggested that abnormal degradation of vWF occurred in the kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)     

Elevation of urinary betaig-h3, transforming growth factor-beta-induced protein in patients with type 2 diabetes and nephropathy

Transforming growth factor-beta (TGF-beta) is a pro-sclerotic growth factor implicated in the pathogenesis of diabetic nephropathy. betaig-h3 is an extracellular matrix protein which is induced in many cells by TGF-beta. This study examined urinary betaig-h3 excretion in diabetic patients with elevated urinary albumin excretion and the clinical application of urinary betaig-h3 as a marker of diabetic nephropathy. Urinary and serum betaig-h3 levels were determined by enzyme-linked immunosorbent assay in 163 type 2 diabetic patients and 101 healthy control subjects of comparable age and weight. The ratio of urinary betaig-h3 and TGF-beta to creatinine was analyzed in patients with different degree of nephropathy. The betaig-h3 to creatinine ratio in urine was elevated in all groups of type 2 diabetics with normoalbuminuria (101.6 +/- 9.27), microalbuminuria (120.2 +/- 14.48), and overt proteinuria (146.3 +/- 16.34), when compared with control subjects (64.8 +/- 7.14) (P < 0.01). There was a positive correlation between urinary betaig-h3 and TGF-beta excretion rate and a positive correlation between urinary betaig-h3 and albumin excretion rate (AER). These data show that urinary levels of betaig-h3 are elevated in type 2 diabetic patients with nephropathy and may be used as a marker of diabetic nephropathy.     

Coronary arterial calcification is associated with albuminuria in type 2 diabetic patient

AIM: Although microalbuminuria has been suggested as an independent risk factor for ischemic heart disease, the relationship between diabetic nephropathy and macroangiopathy remains unclear. Previously, we reported that coronary artery calcification detected by electron beam computed tomography (EBCT) could indicate the degree of coronary atherosclerosis in type 2 diabetic patients. In this study, we examine the association between coronary arterial calcification and microalbuminuria and aortic calcification and microalbuminuria. METHODS: Two hundred and fifty-six patients, including 177 type 2 diabetic patients (106 patients with normoalbuminuria, 71 with microalbuminuria) and 79 non-diabetic patients were evaluated by assessing the urinary albumin excretion rate and using EBCT to determine a coronary calcification score (CCS) and an aortic calcification score (ACS). RESULTS: No differences were observed regarding age, smoking index or BMI. Diabetic patients exhibited a greater CCS than non-diabetic subjects (non-diabetes 33 +/- 75 vs. diabetes 203 +/- 467, p < 0.05). Diabetic patients with microalbuminuria exhibited the most advanced CCS (253 +/- 491, p < 0.05). In contrast, no difference was observed in ACS among three groups. Multiple regression analysis showed that CCS is significantly associated with urinary albumin excretion rate as well as age, duration of diabetes and serum creatinine (R(2) = 0.31), while ACS is strongly associated with age, smoking, serum creatinine, systolic blood pressure and low-density lipoprotein cholesterol level (R(2) = 0.29). CONCLUSION: Increased urinary albumin excretion is associated with coronary arterial calcification in diabetic patients.