尿微量白蛋白和软铁蛋白测定在2型糖尿病肾病筛选中的价值

选择尿常规检查蛋白阴性的2型糖尿病患者500例，糖尿病病程2个月－5年。采用酶免疫法测定24小时尿蛋白排泄率（VAER）、尿微量白蛋白（UAC）、尿转铁蛋白（UTC）。VAER为20－200μg/min患者120例。排除其他原因所致的蛋白尿，诊断为早期糖尿病肾病或糖尿病肾病微量白蛋白尿期。以VAER为金标准，计算UAC、UTC在不同截断点时的敏感度的特异度，根据ROC曲线确定最佳截断点，并比较这两项检查在糖尿病肾病筛选中的价值。结果：UAC最佳截断点为20mg/L，敏感度为83．3％，特 异度为92．1％；UTC最佳截断点为1mg/L，敏感度为91．7％，特异度为89．5％。认为随机尿UAC和UTC在早期糖尿病肾病筛选中的敏感度和特异度均较高，UTC比UAC有更高的敏感度，但特异度较前者差。     

2型糖尿病肾病患者血清血红素加氧酶-1检测的临床意义

目的 探讨2型糖尿病肾病患者血清血红素加氧酶-1(HO-1)的变化及意义.方法 将225例2型糖尿病患者根据尿微量白蛋白排泄率(UAER)分为3组:单纯糖尿病组96例(UAER＜ 30 mg/24 h),早期肾病组71例(30 mg/24 h≤UAER ＜300 mg/24 h),临床肾病组58例(UAER＞300 mg/24 h).另选取60例健康体检者作为对照组.采用酶联免疫吸附试验(ELISA)测定患者血清HO-1及丙二醛浓度,并比较各组HO-1的水平.结果 2型糖尿病肾病患者血清HO-1及丙二醛水平较单纯糖尿病组及对照组明显升高(P均＜0.01).糖尿病肾病患者中,临床肾病组HO-1水平明显高于早期肾病组(P＜0.01).Pearson相关分析显示,HO-1与UAER呈正相关(r=0.485,P＜0.01).结论 血清HO-1检测在2型糖尿病肾脏损伤早期即出现异常,并随着肾脏损害程度的加重而升高,其在2型糖尿病肾病的早期诊断及预测疾病进展中具有一定的临床意义.     

血浆同型半胱氨酸与2型糖尿病尿白蛋白的关系

目的探讨血浆同型半胱氨酸(Hcy)与2型糖尿病(DM)患者的尿白蛋白的关系.方法通过对80例2型DM患者及30例正常人测定Hcy、空腹血糖(FPG)、餐后2小时血糖(2hPG)、糖化血红蛋白(HbA1c)、总胆固醇(TC)、甘油三脂(TG)、尿素氮(BUN)、肌酐(Cr)、尿微量白蛋白排泄率(UAER).据UAER作为指标,将全部80例DM患者分成正常尿微量白蛋白排泄率组(UAER＜30mg/24h为Ⅰ组)、早期糖尿病肾病组(UAER≥30mg/24h、＜300mg/24h为Ⅱ组)、临床糖尿病肾病组(UAER≥300mg/24h或尿蛋白定量＞500mg/24h为Ⅲ组).四组的Hcy进行统计学的比较.结果Ⅲ组比Ⅰ、Ⅱ组(P分别为＜0.01、＜0.05)、Ⅱ组比Ⅰ组(P＜0.05)及Ⅰ、Ⅱ、Ⅲ组均比对照组(P值分别为＜0.05、＜0.01、＜0.01)的血浆Hcy水平高.存在高Hcy血症的2型DM患者,其UAER升高即早期糖尿病肾病发生率明显高于无高Hcy血症的患者.结论高Hcy血症与2型DM的尿白蛋白呈正相关系,其机制可能是通过血管内皮损伤有关.     

多项检测指标在2 型糖尿病早期肾损伤中的诊断价值

目的 分析尿白蛋白/ 肌酐比值(ACR)、尿α1-微球蛋白(α1-MG)、尿β2-微球蛋白(β2-MG)和血清胱抑素C(CysC)在2 型糖尿病早期肾损害中的诊断价值。方法 选取2019 年5 月至2020 年1 月芜湖市中医医院收治的2 型糖尿病患者108 例,根据尿蛋白排出率(UAER)将患者分为单纯糖尿病组(UAER <30 mg/ 24 h)68 例和糖尿病肾病组(30 mg/ 24 h≤UAER<300 mg/ 24 h)40 例。并选取同期健康体检者30 例为健康对照组。观察各组尿ACR、尿α1-MG、尿β2-MG 和血清CysC 水平并进行统计学比较。绘制受试者工作特征(ROC)曲线预测各指标对早期糖尿病肾损伤的曲线下面积(AUC),并计算各指标的敏感度和特异度。结果 糖尿病肾病组和单纯糖尿病组的尿ACR、尿α1-MG、尿β2-MG 和血清CysC 水平明显高于健康对照组(P 均<0. 05)。糖尿病肾病组的尿ACR、尿α1-MG、尿β2-MG 和血清CysC 水平明显高于单纯糖尿病组(P 均<0. 05)。尿ACR、尿α1-MG、尿β2-MG 和血清CysC的曲线下面积分别为0. 923、0. 851、0. 755 和0. 702,敏感度分别为84. 4%、75. 0%、71. 9%和62. 5%,特异度分别为96. 4%、85. 5%、81. 8%和67. 3%。结论 尿ACR、尿α1-MG、尿β2-MG 和血清CysC 在糖尿病早期肾损伤的进程中有着重要的作用,其测定有助于糖尿病肾病的早期诊断,为临床诊治提供可靠的依据。     

糖尿病肾病早期诊断的研究进展

本文综述近年来有关糖尿病肾病(DN)早期诊断的研究进展. 1微量白蛋白尿(UMA1b)微量白蛋白尿是目前优选的早期诊断指标.尿白蛋白排泄率(UAER)20～200ug/min为微量白蛋白尿,如果6个月内连续尿液检查有两次UAER在30～300mg/24h之间,并排除其他可能引起UAER增加的原因,如酮症酸中毒、泌尿系统感染、运动、原发性高血压,心力衰竭等,即可诊断早期DN.但是UAER的增加并非DN特异的,故对病程＜6年的糖尿病病人需除外其他肾病可能.近20年大量的临床研究[1].已证实UAER增加与HbA1c血糖控制、血压、蛋白摄入高度相关,并与心血管病死亡率、增殖性视网膜病变发生均相关.在DN早期积极控制高血压、糖尿病有益于延缓或阻止DN的进一步发展与恶化.     

尿转铁蛋白测定在糖尿病肾病早期诊断中的临床意义

目的探讨尿转铁蛋白(TRF)在糖尿病肾病(DN)早期诊断中的临床意义。方法分正常人组及糖尿病组,留取晨新鲜尿测定对比尿微量白蛋白(UAER)及转铁蛋白(TRF)。结果糖尿病病人中蛋白尿组和尿微量白蛋白正常组转铁蛋白升高者分别为100%、26.5%,差异有非常显著意义(PO.01)。结论转铁蛋白可以作为更敏感的糖尿病肾病早期诊断指标。     

随机尿微量白蛋白肌酐比值在糖尿病肾损伤患者诊疗中的应用分析

目的 分析糖尿病肾损伤患者诊疗中随机尿微量白蛋白肌酐比值的应用.方法 回顾性选取2020年2月—2021年2月该院糖尿病患者90例为研究对象,依据肾损伤程度分为24 h尿白蛋白排泄率(UAER)＜30 mg/24 h组(正常白蛋白尿组)、UAER 30～300 mg/24 h组(微量白蛋白尿组)、UAER＞300 mg...     

血清胎球蛋白A对糖尿病肾病早期诊断的临床意义

目的比较不同尿白蛋白排泄状态的2型糖尿病患者血清胎球蛋白(Fetuin)-A变化,探讨Fetuin-A在糖尿病肾病(DKD)早期诊断中的临床价值。方法纳入170例糖尿病患者,依据尿微量白蛋白排泄率(UAER)分为正常白蛋白尿(NA)组、微量白蛋白尿(MA)组、临床肾病(CN)组,并选取60例健康体检者作为对照(NC)组,检测各组Fetuin-A的血清水平。结果 NC组、NA组、MA组和CN组血清Fetuin-A水平分别为(215.50±31.42)mg/L、(290.81±36.56)mg/L、(369.85±53.51)mg/L和(460.06±78.65)mg/L,组间具有统计学差异(P0.001);在糖尿病患者中,血清Fetuin-A水平与病程、体重指数(BMI)、空腹血糖(FPG)、糖化血红蛋白(HBA1c)、三酰甘油(TG)、尿素(Urea)、肌酐(Crea)和UAER呈正相关,与高密度脂蛋白胆固醇(HDL-C)呈负相关;受试者工作特征(ROC)曲线分析结果显示,Fetuin-A用于诊断糖尿病患者是否发生微量白蛋白尿的曲线下面积(AUC)为0.889;用于鉴别诊断微量白蛋白尿和临床肾病患者的AUC为0.817。结论 Fetuin-A在糖尿病患者中水平升高,且与UAER正相关,Fetuin-A用于判断糖尿病患者是否发生MA具有一定的临床价值。     

尿铜蓝蛋白、血清胱抑素C、视黄醇结合蛋白联合检测在早期糖尿病肾病中的诊断价值

目的探讨尿铜蓝蛋白、血清胱抑素(Cys)C和视黄醇结合蛋白(RBP)三者在早期糖尿病肾病(DN)中的诊断价值。方法糖尿病患者参照尿微量白蛋白排泄率(UAER)分成两组:早期DN组38例(30 mg/24 hUAER300 mg/24 h)和单纯糖尿病组44例(UAER30 mg/24h);健康体检者38例作为正常对照组。比较三组尿铜蓝蛋白、Cys C和RBP水平。结果三组尿铜蓝蛋白、Cys C、RBP水平均有显著差异(P0.01),且DN组最高,正常对照组最低;尿铜蓝蛋白、Cys C、RBP三者联合检测对于DN诊断的曲线下面积为0.948,敏感性为91.42%,特异性为90.51%,均显著高于三者单独检测。结论尿铜蓝蛋白、Cys C、RBP三者联合检测对于早期DN的诊断有着重要的意义。     

测定外周血内CysC及Hcy水平在早期糖尿病肾病临床诊断中应用价值的分析

目的探讨测定外周血内CysC及Hcy水平在早期糖尿病肾病(diabetic nephropathy,DN)临床诊断中的应用价值。方法选取2017年6月—2018年6月该院收治的2型糖尿病(T2DM)患者122例为研究对象,将UAER30 mg/24 h者纳入单纯T2DM组(64例),将UAER介于30～300 mg/24 h者纳入早期DN组(58例)。并选取同期健康体检者60例为对照组。检测并比较三组受检者外周血的Scr、BUN、CysC及Hcy水平;分析CysC、Hcy水平与UAER值的相关性,并绘制ROC曲线来检验CysC、Hcy水平对早期DN诊断效力。结果各组间Scr、BUN水平相比,差异无统计学意义(P0.05);单纯T2DM组、早期DN组的Cysc、Hcy水平均显著高于对照组,且早期DN组显著高于单纯T2DM组,差异有统计学意义(P0.05);Pearson相关性分析结果显示,CysC、Hcy水平与UAER均呈显著正相关(r=0.719、0.694,P0.05);CysC诊断早期DN的AUC为0.893,最佳临界值为1.3 mg/L,敏感度、特异度分别为0.881、0.832;Hcy诊断早期DN的AUC为0.887,最佳临界值为13.55 mg/L,敏感度、特异度分别为0.841、0.876; CysC联合Hcy诊断早期DN的AUC为0.961,最佳临界值分别为1.3 mg/L、13.55 mg/L,敏感度、特异度分别为0.910、0.891。结论测定外周血内CysC及Hcy水平在早期DN临床诊断中具有重要价值,值得临床推广。     

西洛他唑对2型糖尿病尿白蛋白排泄率的影响

目的探讨西洛他唑治疗2型糖尿病早期肾病的临床疗效.方法将60例血压正常伴微量白蛋白尿的2型糖尿病患者,随机分为两组：治疗组30例,予口服西洛他唑片（50 mg,bid）;对照组30例,予口服安慰剂维生素B1（10 mg,bid）,两组均治疗3个月.观察患者治疗前后尿白蛋白排泄率（UAER）的变化.结果治疗组与治疗前比较,UAER明显下降（P＜0.01）,下降幅度达51.6%,约3%病人仅有轻微头痛反应.对照组治疗前后UAER无明显变化（均P＞0.05）.结论西洛他唑能显著降低糖尿病尿白蛋白的排泄,对糖尿病早期肾病具有治疗作用,且安全性好.     

Evaluation of a dipstick test for microalbuminuria in three different clinical settings, including the correlation with urinary albumin excretion rate.

A dipstick test for microalbuminuria was compared with urinary albumin excretion and urinary albumin concentration. Elevated urinary albumin excretion was defined as > 30 mg/24 h, elevated urinary albumin concentration in early morning urine as = > 20 mg/l and sticks = > 20 mg/l were considered positive. 1,071 samples with urinary albumin concentration 20-200 mg/l from 258 diabetic subjects were evaluated in three settings: I. 3 trained nurses testing samples from day-clinic diabetic patients. Sticks v.s. urinary albumin excretion sensitivity 86%, specificity 97%, predictive value of negative test 97%, correlation coefficient 0.79. Values for same setting but v.s. urinary albumin concentration were almost identical. II. 1 laboratory technician testing not-hospitalised diabetic patients: Sticks v.s. urinary albumin concentration: sensitivity 91%, specificity 85%, predictive value of negative test 95%, correlation coefficient 0.82. III. 58 general practitioners testing not-hospitalized diabetic patients: Sticks v.s. urinary albumin concentration: sensitivity 66%, specificity 92%, predictive value of negative test 83%, correlation coefficient 0.70. Conclusions: In the hands of trained nurses and laboratory technician the Micral-Test showed good correlation with urinary albumin excretion and urinary albumin concentration for day-clinic and not-hospitalized patients and can be recommended as a screening tool. General practitioners obtained a lower sensitivity probably due to lack of experience and incorrect handling of the sticks leading to systematical errors. Training in the use of the stick must be emphasized, since under such circumstances the results are satisfactory.     

Semi-quantitative determination of microalbuminuri by urinary dipstick

Microalbuminuria predicts subsequent clinical nephropathy and mortality in diabetic patients. This study was undertaken to determine the usefulness of a new immunochemical urinary dipstick test (Micral-Test, Boehringer Mannheim, GmbH Mannheim, Germany) in identifying urinary albumin concentrations within the microalbuminuric range (urinary albumin concentration 20–200 mg/L). Twenty-four hour urine specimens were collected from 298 consecutive diabetic outpatients. Micral-Test was performed by two laboratory scientists blinded to each other's results and those of radioimmunoassay (RIA) and immunoturbidimetry on the same specimen. When compared with RIA, Micral-Test had an overall sensitivity of 92.2%, specificity of 92.3% and positive predictive value of 86.4%. However, at the threshold value of 20 mg/l Micral-Test showed false positive results in 37.8% of samples when compared with RIA. Similar results were obtained when Micral-Test was compared with immunoturbidimetry. We conclude that Micral-Test is a useful screening method for the detection of microalbuminuria. We suggest that positive tests be confirmed by a timed urine collection using established methodology and that patients whose Micral-Test is negative be subjected to annual retesting.     

Screening for Early Diabetic Nephropathy: Which Sample to Detect Microalbuminuria?

In a study to monitor the acceptability of using a timed overnight urine collection to measure microalbuminuria in a large diabetic population, it was found that only 184 (69.4%) of 265 diabetics returned the urine collection to the hospital laboratory. Three proposals for an initial screening test to predict high risk microalbuminuria were analysed. Proposal I: a random urinary albumin concentration (RAC) greater than 25 micrograms/ml predicts an overnight albumin excretion rate (AER) greater than 30 micrograms/min. In 159 diabetics, the sensitivity of this screening test was 56%, specificity 81%, and predictive value 15%. Proposal II: an albumin concentration greater than 20 micrograms/ml in an early morning urine sample predicts an overnight AER greater than 30 micrograms/min. In 175 diabetics, the sensitivity of this screening test was 86%, specificity 97%, and predictive value 71%. Proposal III: an albumin/creatinine ratio (albumin mg/l creatinine mmol/l) greater than 3.5 in an early morning urine sample predicts an overnight AER greater than 30 micrograms/minute. In 171 diabetics, the sensitivity of this screening test was 100%, specificity 95%, and predictive value 64%. It is concluded that an albumin/creatinine ratio performed on an early morning urine sample brought to the diabetic clinic would be a useful initial screening test to detect an overnight AER greater than 30 micrograms/min.     

2型糖尿病患者尿白蛋白排泄率与补体C5a的关系

目的探讨2型糖尿病患者血、尿补体活化片段C5a含量的变化与糖尿病肾病的关系。方法选2型糖尿病患者39例,健康体检者21名作为对照,检测血、尿C5a浓度以及血高敏C反应蛋白,测定尿白蛋白排泄率以及血糖控制情况,分析其关系。结果与对照组比较,2型糖尿病患者尿C5a浓度升高（11．4±21．1vs76．3±144．4,P〈0．05）,血C5a无明显变化,尿C5a与尿白蛋白排泄率正相关（r=0．378,P〈0．05）,糖尿病病程、尿C5a是尿白蛋白排泄率的独立预测因素。结论补体活化可能与糖尿病肾病的发生有关。     

Assessing urinary levels of IL-18, NGAL and albumin creatinine ratio in patients with diabetic nephropathy

AimsDiabetic nephropathy (DN) is a serious microvascular complication of a longstanding hyperglycemia. This study aims to evaluate whether urinary neutrophil gelatinase-associated lipocalin (NGAL) and urinary Interleukin-18 possess a better diagnostic value than albumin creatinine ratio in assessing the severity of nephropathy in patients with type 2 diabetes mellitus (T2DM).Material & methodsNinety participants diagnosed with T2DM were recruited and they were divided into three study groups according to their albumin/creatinine ratio (ACR): (Normoalbuminuria group, Microalbuminuria group, and Macroalbuminuria group). A matching of Ninety healthy subjects were included as controls. Blood and urine samples were collected to measure various markers of glycemic control and kidney function.ResultsIL-18 levels were not changed significantly between all study groups (P > 0.05), despite a significant positive correlation between IL-18 and urinary albumin levels.NGAL levels were significantly increased in Microalbuminuria group and Macroalbuminuria group as compared to the control and Normoalbuminuria groups. NGAL was also positively correlated with urinary albumin and ACR, but negatively correlated with the age and body mass index. Receiver Operating Characteristic curves revealed that for early detection of DN, the best cutoff values to discriminate DN and diabetic without nephropathy groups were ˃ 21.4 ng/ml for NGAL (94.67 sensitivity, 26.67% specificity), ≤0.34 pg/mL for IL-18 (72% sensitivity, 53.33% specificity), and ˃29.8 mg/g for ACR (80% sensitivity, 100% specificity).ConclusionWe conclude that the urinary ACR is a more accurate individual biomarker of DN when compared to both NGAL and IL-18.     

Albuminuria and associated medical risk factors: A cross-sectional study in 476 type I (insulin-dependent) diabetic patients. Part 1

Albumin concentration in a morning urine sample was analyzed in a cross-sectional study in 476 insulin-dependent diabetic patients. The following groups of patients were defined: A) normal urinary albumin (urine albumin <12.5 mg/L); B) high normal albuminuria (12.5–30 mg/L); C) microalbuminuria, ie, incipient nephropathy (31–299 mg/L); and D) clinical nephropathy (≥300 mg/L). The prevalences of incipient and clinical diabetic nephropathy were 24.8 and 14.4%, respectively. There were no differences in clinical parameters such as age, age at onset or duration of diabetes, blood pressure, serum creatinine, or HbA_1c levels between groups A and B. The frequency of retinopathy in these groups was 55 and 50%, respectively. In group C, there were increases in age, duration of diabetes, blood pressure, serum creatinine, and HbA_1c levels. The frequency of retinopathy was higher (80%), and more patients had severe forms (47%). In group D, there were further increases in all parameters and, in addition, younger age at onset of diabetes. The frequency of retinopathy was 97%, and severe forms of retinopathy were more common (86%). Seventeen percent of the patients were treated for hypertension. These patients were older, had longer duration of diabetes, and had higher levels of blood pressure, serum creatinine, and urinary albumin, as well as a younger age at onset of diabetes than patients not requiring antihypertensive treatment.     

Albuminuria and associated medical risk factors: A cross-sectional study in 451 type II (noninsulin-dependent) diabetic patients. Part 2

The association between urinary albumin concentration (UAC) in a morning urine sample and medical risk factors was evaluated in a cross-sectional study of 451 type II (noninsulin-dependent) diabetic patients. The following four groups of patients were created according to their urinary albumin levels: A) normal (<12.5 mg/L); B) high normal (12.5–30 mg/L); C) microalbuminuria, ie, incipient nephropathy (31–299 mg/L); and D) clinical nephropathy (≥300 mg/L). The patients with high normal levels had higher HbA_1c and systolic blood pressure levels than patients with values within normal limits. The prevalence of incipient and clinical diabetic nephropathy was 20 and 7%, respectively. Incipient nephropathy was associated with higher blood pressures and body weights. Patients with clinical nephropathy had even further increases in these parameters, were older, and had longer duration of diabetes. In both groups of nephropathy, men were preponderant. Thirty six percent of all patients and 73% of patients with clinical nephropathy were treated for hypertension; 55% were treated with insulin. The insulin-treated patients had poorer metabolic control, but there were no differences in blood pressure or serum creatinine levels as compared with those of patients not receiving insulin treatment. The proportion of patients with severe retinopathy increased with the degree of albuminuria, although 22% of the patients with clinical nephropathy continued to be nonretinopathic.     

Current therapeutic management of diabetic nephropathy

Roughly 40% of all patients with insulin-dependent diabetes mellitus (IDDM) develop diabetic nephropathy with proteinuria, hypertension and a decrease in glomerular filtration rate 10 to 20 years after the onset of the disease, and 5 years later most patients suffer from end-stage renal disease. Microalbuminuria, defined as an urinary albumin excretion rate (UAER) between 30 and 300 mg/day, strongly predicts the development of nephropathy in IDDM. Nearly all patients with IDDM, a decreasing glomerular filtration rate and a UAER >300 mg/day have coexisting hypertensive disease additionally worsening renal function. We review the results of recent long-term studies of the current therapeutic management in diabetic patients by means of better blood pressure control, low-protein diet and near-normal blood glucose control in the early microalbuminuric phase as well as in the later phases of the disease characterized by diabetic nephropathy with a UAER >300 mg/day. Since the large majority of studies have been performed on IDDM, our conclusions with regard to therapy are only valid in this subgroup of diabetic patients.