Determination of urinary enzymes as a marker of early renal damage in diabetic patients

Diagnosis of diabetic nephropathy in the early stages is very important since there are no clinical signs or symptoms. Urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion has been recommended as a tubular dysfunction marker that elevates before other markers, such as microalbuminuria and a decrease in creatinine clearance. In this study, we compared excretion of urinary enzymes with other markers that are used routinely in diabetic nephropathy assessment. Urinary NAG, lactate dehydrogenase (LDH), alkaline phosphatase (AP) activities, urea, creatinine, and albumin, with levels of serum glucose and creatinine and whole blood glycosylated hemoglobin (HbA1c) were measured in 32 diabetes mellitus patients and 25 healthy subjects (controls). Notably, urinary NAG, AP, LDH excretion, and microalbuminuria in the diabetic patients group were significantly increased compared to those in the control groups (P<0.001, P<0.05, P<0.01, and P<0.01, respectively). Meanwhile, our results showed that the urinary NAG excretion had the highest sensitivity and specificity (100% and 87.5%, respectively) compared to other markers. We showed that measuring urinary NAG excretion could be useful for the assessment of renal failure in diabetes mellitus patients and confirmed the use of NAG as a routine screening test.     

醛固酮受体拮抗剂治疗糖尿病肾病的临床研究

目的:探讨应用醛固酮受体拮抗剂能否改善糖尿病肾病患者的炎症病变、减少糖尿病肾病患者的蛋白尿排泄。方法:采用前瞻性随机对照方法,对糖尿病肾病(Ⅲ、Ⅳ期)患者60例,按照1:1分为治疗组(螺内酯)和对照组(安慰剂),予ACEI类或AT1RA类的药物治疗基础上加用螺内酯片(20mg/d)或安慰剂,共治疗12周。检测治疗前后24h尿微量白蛋白、尿单核细胞趋化蛋白-1(MCP-1)、肾功能等情况。结果:治疗后两组的肌酐清除率均较治疗前升高,但治疗组治疗前后比较差异有非常显著性(59.4±13.4,61.2±13.5,P=0.000)。两组治疗前后的24h尿微量白蛋白及尿MCP-1比较差异均有显著性(P<0.05),但治疗组治疗前后24h尿微量白蛋白及尿MCP-1比较差异有非常显著性(1450.13±1369.84,779.33±656.57,P=0.001;39.69±9.71,32.79±6.74,P=0.000)。治疗前后二者定量呈明显正相关。结论:醛固酮受体拮抗剂能改善糖尿病肾病患者的炎症病变,明显减少蛋白尿排泄,延缓了糖尿病肾病的进展。     

尿N-乙酰-β-D-氨基葡萄糖苷酶对监测早期肾功能损害的价值

目的探讨尿N-乙酰-β-D-氨基葡萄糖苷酶（NAG）监测早期肾功能损坏的价值。方法根据内生肌酐清除率（Ccr）将120例肾病患者分为A、B两组,A组58例,其Ccr≥80mL／min。B组62例,其Ccr〈80mL／min。分别检查A、B．两组和50例健康人的尿NAG（U／mmol Cr）,并与其尿微量清蛋白[mAlb（mg／mmol Cr）]和血肌酐（Cr）含量进行比较。结果A、B两组肾病患者尿NAG、rnAlb检测结果显著高于健康对照组,差异有统计学意义（P〈0．05）,B组患者尿NAG、mAlb检测结果显著高于A组,差异有统计学意义（P〈0．05）;在A、B两组中,尿NAG的阳性率显著高于尿mAlb和血Cr,差异也有统计学意义（P〈0．05）;肾病患者尿NAG活性与Ccr具有良好的相关性,差异有统计学意义（r=0．876,P〈0．05）。结论尿NAG在肾病早期有较高的检出率,可作为监测早期肾功能损害的敏感指标。     

N-Acetyl-beta-D-glucosaminidase levels and diabetic microangiopathy.

N-Acetyl-beta-D-glucosaminidase (NAG) activity has been measured in the serum and urine of primary and secondary diabetics and in primary diabetics with microangiopathy. NAG activity has also been measured in the tears of diabetics with ocular complications and diabetics with no ocular changes. Results have shown significantly higher levels of urinary NAG in diabetics with proteinuria (p less than 0.001) and proteinuria and retinopathy (p less than 0.001). There was no correlation between urinary NAG activity and serum creatinine (r = 0.28) or urinary NAG and the degree of proteinuria (r = 0.24). Increased urinary NAG levels were also observed in secondary diabetes associated with haemochromatosis and acromegaly. Significantly higher serum NAG levels were found in newly diagnosed diabetics (p less than 0.01) and significantly lower levels in chemical diabetics (p less than 0.01). Compared to non-diabetic controls tear NAG levels were significantly higher in the diabetic controls (p less than 0.01), in diabetics with retinopathy (p less than 0.01), and in diabetics with cataract formation (p less than 0.05). An assessment of this enzyme is made in relation to the development of diabetic microangiopathy.     

THE SIGNIFICANCE OF URINARY N-ACETYL-ß-D-GLUCOSAMINIDASE FOR PREDICTING EARLY STAGE DIABETIC NEPHROPATHY

We studied urinary N-acetyl-ß-D-glucosaminidase (NAG) in the early stage of diabetic nephropathy in 27 non-insulin-dependent diabetes mellitus (NIDDM) patients with a microalbumin level below 20 mg on 24-hour urine sample. Microalbumin and NAG excretion were measured in 24-hour urine samples collected on three separate occasions within seven days of admission. Creatinine clearance was determined simultaneously. There was a significant negative correlation between the creatinine clearance and 24-hour urinary NAG (r=-0.38, p<0.05). Elevation of urinary NAG may indicate decreased renal function during early stage NIDDM nephropathy.     

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.     

血清BLyS和APRIL水平与系统性红斑狼疮关联性研究

目的：探讨系统性红斑狼疮（SLE）患者血清B淋巴细胞刺激因子（BLyS）和增殖诱导配体（APRIL）蛋白水平与疾病活动性的关系。方法：应用酶联免疫吸附试验（ELISA）法检测SLE活动组（13例）和SLE缓解组（10例）患者血清BLyS和APRIL水平,以健康志愿者（23例）作为对照;同时将血清BLyS和APRIL水平与患者的临床检验指标（尿蛋白、抗dsDNA抗体）分组进行分析。结果：SLE患者组血清BLyS水平高于健康对照组,且活动期高于缓解期（P〈0.05）;尿蛋白阳性组血清APRIL水平明显低于尿蛋白阴性组患者（P〈0.05）;抗dsDNA抗体升高组血清BLyS和APRIL均高于抗dsDNA抗体滴度正常组,但均无统计学意义。结论：SLE患者血清BLyS水平增高,且增高与疾病的活动性有关;尿蛋白阳性组血清APRIL水平明显低于尿蛋白阴性组SLE患者,提示BLyS和APRIL可能参与SLE的发病过程。     

Clinical value of urinary kidney biomarkers for estimation of renal impairment in elderly Chinese with essential hypertension

The purpose of this work was to observe the excretion of specific types of urinary proteins and urinary enzymes in elderly essential hypertension patients, for early detection and targeted treatment of hypertensive nephropathy in the elderly. A total of 120 elderly essential hypertensive patients and 38 healthy elderly volunteers were involved. The urinary excretion rate of retinal-binding protein (RBP), transferrin (Tf), albumin (Alb), and urinary enzyme N-acetyl-beta-D-glucosaminidase (NAG) activity were determined. Patients were divided into two groups according to their creatinine clearance (Cockroft-Gault formula). There were 88 patients in group A, whose glomerular filtration rate (GFR) was >or=80 mL/min, and 32 patients in group B with a GFR <80 mL/min. Among the essential hypertensive patients, urinary excretion rates of RBP, Alb, Tf, and NAG were increased in both groups compared with the healthy controls. But the amount of urinary protein differed between group A and group B. The excretion rate of specific urinary protein and urinary enzyme had a positive relationship with the duration of course of hypertension. We believe that specific types of urinary proteins and urinary enzymes may be useful markers for early diagnosis of hypertensive nephropathy; they can also be regarded as a clinical indicator of the progression of hypertensive nephropathy, serving in the assessment of therapeutic effects.     

Urinary glycosaminoglycan excretion in rheumatic diseases.

We used Alcian Blue (AB) and dimethylmethylene blue (DMB) methods to measure glycosaminoglycan (GAG) excretion in the first morning urine specimens of patients with osteoarthritis (OA), ankylosing spondylitis (AS), and rheumatoid arthritis (RA) in different stages of disease. By the AB method, urinary GAG excretion in patients with RA was not different from healthy control subjects. However, the DMB method showed significant differences (in milligrams of GAG per gram of creatinine) for OA (median 25.4, range 14.3-44.0, P less than 0.01, n = 23) and RA patients (median 33.0; range 10.0-147.6; P less than 0.001, n = 63) in comparison with unaffected individuals (median 20.2; range 8.9-41.4, n = 38). We noted a significant difference in urinary GAG excretion between RA and OA patients (P less than 0.01) and between RA and AS (P less than 0.01) patients. The DMB method was further investigated by clinical decision analysis. The DMB method is simple and rapid and may be useful in diagnosing RA by distinguishing between RA and OA or AS.     

氯沙坦对2型糖尿病肾病患者尿转化生长因子β1的影响

目的通过检测糖尿病肾病患者尿转化生长因子β1(TGFβ1水平,探讨患者肾脏纤维化状况及氯沙坦对肾脏纤维化的影响。方法检测33例2型糖尿病肾病患者氯沙坦(50 mg/d×8周治疗前后24 h尿蛋白、尿肌酐,尿TGFβ1和肌酐。尿TGFβ1检测方法为ELISA法。20例健康志愿者的尿液标本作为对照组。结果糖尿病肾病患者尿TGFβ1明显高于正常对照组,经氯沙坦治疗后尿TGFβ1浓度明显下降(P<0.001。尿TGFβ1浓度变化与尿蛋白变化具有相关性(P<0.01)。结论氯沙坦通过降低糖尿病肾病患者尿TGFβ1水平发挥抗肾脏纤维化作用,这是氯沙坦延缓糖尿病肾病进展的机制之一,这一表现先于蛋白尿的减少。     

系统性红斑狼疮患者外周血单个核细胞干扰素诱导的蛋白10mRNA表达的临床价值

目的 探讨外周血单个核细胞（PBMCs）干扰素诱导的蛋白10（IP-10）mRNA表达与系统性红斑狼疮（SLE）活动的关系。方法 用逆转录-聚合酶链反应（RT—PCR）检测46例SLE患者、20例类风湿关节炎（RA）患者、11例非SLE肾损伤患者及20名正常健康人PBMCSIP-10mRNA表达。结果 SLE活动组PBMCSIP-10mRNA表达水平与非活动组间的差异有统计学意义（P〈0．01），活动性狼疮肾炎（LN）组与无肾损伤组之间PBMCSIP-10mRNA表达水平的差异亦有统计学意义（P〈0．05），而RA组和非SLE肾病组患者与正常对照组水平相近似（P〉0．05）。血清IP—10水平与PBMCSIP-10mRNA表达高度正相关（r=0．8971，P〈0．01）。PBMCSIP-10mRNA表达水平与狼疮病活动指数（SLEDAI）评分呈正相关（r=0．6837，P〈0．01），与肾SLEDAI评分亦高度正相关（r=0．7260，P〈0．01）。结论 SLE活动时期PBMCSIP-10mRNA表达增加，与SLE疾病活动状况相关，尤其与LN的活动状况密切相关。     

Dose-dependent effect of rosuvastatin treatment on urinary protein excretion

Concerns have been raised because of observations of proteinuria associated with rosuvastatin treatment. In this open-label study, a potential dose-dependent effect was investigated of rosuvastatin on urinary protein excretion and renal function parameters in 90 hyperlipidemic patients randomly assigned to rosuvastatin 10 mg/day (n = 45) or 20 mg/day (n = 45). Urinary samples were collected from patients and 40 age- and gender-matched controls to determine electrolyte, uric acid, creatinine, and protein (total, albumin, IgG, and alpha1-microglobulin) levels at baseline and after 12 weeks. A dose-dependent increase in the excretion of alpha1-microglobulin (17.6% in rosuvastatin 10 vs 34.9% in rosuvastatin, 20 mg/day; P = .03 for the comparison between groups) was observed. A trend toward an increase in the estimated glomerular filtration rate was noted in only patients receiving 20 mg/day of rosuvastatin. These findings indicate that rosuvastatin treatment increases the urinary excretion of alpha1-microglobulin urinary excretion in a dose-dependent manner without adversely affecting renal function.     

Expression modes of urinary N-acetyl-beta-D-glucosaminidase in patients with chronic renal insufficiency

BACKGROUND: Urinary N-acetyl-beta-D-glucosaminidase (NAG) activity has emerged as potentially useful early marker of renal tubular injury. This activity is usually evaluated in random urine samples and is related to urinary creatinine concentration. Reports about the lack of correlation between NAG activity of 24-h urines and activity of random urine samples in some clinical and experimental situations led us to study the correlation existing between different procedures for expressing urinary NAG in patients with chronic renal insufficiency. METHODS: Thirty samples of 24-h urine and 30 random urine samples from chronic renal insufficiency patients were collected. The activity of urinary NAG was examined fluorimetrically. RESULTS: The following correlations were observed: (1) r = 0.431 (P = 0.017) for activity in random urine samples and total activity in 24-h urines); (2) r = 0.281 (P = 0.005) for activity in random samples and activity, expressed as U/l, in 24-h urines. CONCLUSIONS: The data show that collection of urine excreted over the whole day and evaluation of total daily excretion of NAG seems the method of choice, at least for patients with chronic renal insufficiency.     

尿五种蛋白联合检测对糖尿病肾病早期诊断的临床价值

目的　探讨联合检测尿五种蛋白对早期诊断糖尿病肾病的临床价值。方法　测定 10 4例 2型糖尿病患者 2 4h白蛋白 (Alb)、转铁蛋白 (TRF)、N 乙酰 β D氨基葡萄糖苷酶 (NAG)、免疫球蛋白 (IgG)、视黄醇结合蛋白 (RBP)以及空腹血糖、血尿素氮等指标。根据 2 4h尿白蛋白排泄率 (UAER)分为三组 ,第 1组 :正常白蛋白尿组 (UAER≤ 2 0 μg/min) ,6 1例 ;第 2组 :微量白蛋白尿组 (UAER 2 0～ 2 0 0 μg/min) ,2 5例 ;第 3组 :大量白蛋白尿组 (UAER≥ 2 0 0 μg/min) ,18例。三组之间进行统计学分析。 结果　①三组间年龄、收缩压(SBP)、舒张压 (DBP)差异有显著意义 (P <0 0 5 )。②尿TRF、NAG、IgG和RBP在第 1组增高的频率为9 84 %、4 92 %、4 92 %、8 19% ;在第 2组增高的频率为 96 %、84 %、88%、5 2 % ;在第 3组增高的频率为10 0 %、88 89%、10 0 %、77 78%。③偏相关分析显示 :UAER与尿TRF、NAG、IgG和RBP排泄相关性明显 (r分别为 0 5 6 6 3、0 36 6 8、0 5 4 92和 0 10 77,前三项P均 <0 0 5 ,后者P =0 2 84 )。结论　尿五种蛋白联合检测对糖尿病肾病的早期诊断具有较大的临床价值。     

Urinary N-acetyl-beta-D-glucosaminidase activity does not predict development of diabetic nephropathy

Urinary activity of N-acetyl-beta-D-glucosaminidase (NAG) has been suggested as a marker for diabetic nephropathy. In this study, urinary activity of NAG was measured with an interval of 5 yr in 36 insulin-dependent diabetic subjects to evaluate its predictive value for development of diabetic nephropathy. During the observation period, 9 patients developed detectable signs of diabetic nephropathy. In these patients, urinary albumin concentration had increased to 503 +/- 185 mg/L, compared to 16 +/- 1 mg/L in patients without nephropathy (P less than .01; means +/- SE), and the fractional albumin excretion rate was 0.21 +/- 0.07 X 10(-3), compared to 0.01 +/- 0.00 X 10(-3) (P less than .01). However, the activity of urinary NAG was not different in these patients compared with the patients without nephropathy (0.69 +/- 0.15 and 0.61 +/- 0.09 U/mmol creatinine, respectively). Furthermore, no increase in the activity of urinary NAG was seen during the observation period in either group. We concluded that the urinary activity of NAG is not related to the development of microalbuminuria and therefore cannot be used as a predictor for the development of diabetic nephropathy.     

绝经前女性风湿病患者骨密度变化影响因素分析

目的:对绝经前女性系统性红斑狼疮(SLE)与类风湿关节炎(RA)患者进行骨密度(BMD)的监测,评估发生骨量丢失的原因。方法:采用超声骨密度仪测量89例绝经前女性患者(SLE49例,RA40例)及68例健康志愿者(对照组)右跟骨部位的BMD,同时对患者诸多影响BMD的因素(年龄、病程、疾病活动度、激素使用时间、激素累积剂量及激素日剂量)与BMD进行相关分析及多元回归分析。结果:患者右跟骨部位的BMD(SLE为-1.42±0.56,RA为-1.36±0.63)明显低于对照组(-0.58±0.52,P<0.01),骨质疏松的发生率(SLE为17.1%,RA为13.3%)明显高于对照组(P<0.01)。线性相关分析结果显示SLE患者的BMD与C3呈正相关(r=0.521,P<0.01),与激素累积剂量呈负相关(r=-0.398,P<0.05);BMD与RA患者的CRP呈负相关(r=-0.431,P<0.05)。多元回归分析提示C3下降与激素累积剂量增高为SLE患者BMD下降的独立危险因素,CRP升高为RA患者BMD下降的独立危险因素。结论:绝经前女性SLE与RA患者骨质疏松的发生率较正常人群明显增高。SLE与RA患...     

Atrial natriuretic peptide and urinary dopamine output in non-insulin-dependent diabetes mellitus.

1. Disturbances of sodium and water homoeostasis may contribute to the close association between diabetes, hypertension and proteinuria. We therefore studied the patterns of two natriuretic hormones, plasma atrial natriuretic peptide and urinary dopamine, in 165 Chinese patients with non-insulin-dependent diabetes mellitus controlled by diet or oral hypoglycaemic agents on two occasions over a 6-week period. Patients were divided into three groups based on the mean value of two 24h urinary albumin excretion measurements. In group 1, 88 patients had normoalbuminuria (urinary albumin excretion < or = 30 mg/day), in group 2, 48 patients had microalbuminuria (urinary albumin excretion between 30 and 300 mg/day), and in group 3, 29 patients had macroalbuminuria (urinary albumin excretion > or = 300 mg/day). 2. The supine systolic blood pressure (mean +/- SD) was higher in patients with abnormal albuminuria (group 1: 140.9 +/- 27.4 mmHg; group 2: 158.1 +/- 26.4 mmHg; group 3: 166.7 +/- 23.9 mmHg; F = 13.1, P < 0.001, analysis of variance). Urinary sodium output was similar in these three groups of patients. The geometric means (anti-logarithm of 95% confidence interval logarithm) of plasma atrial natriuretic peptide concentrations increased with increasing proteinuria [group 1: 33.3 (29.9-37.1) pg/ml; group 2: 39.1 (34.2-44.6) pg/ml; group 3: 50 (38.6-54.7) pg/ml; F = 4.24, P < 0.01; analysis of variance], whereas those of urinary dopamine output were related inversely to proteinuria [group 1: 1291.7 (1167.2-1437.0) nmol/day; group 2: 1142.3 (975.9-1337.2) nmol/day; group 3: 982.7 (775.7-1245) nmol/day; F = 3.10, P < 0.05, analysis of variance].(ABSTRACT TRUNCATED AT 250 WORDS)     

羟氯喹联合治疗对IgA肾病残余蛋白尿的影响

目的 探讨羟氯喹(HCQ)联合肾素-血管紧张素系统抑制剂、激素和/或免疫抑制剂对IgA肾病患者残余蛋白尿的影响.方法 纳入2018年9月至2020年8月四川省人民医院活检为IgA肾病的门诊患者,HCQ联合治疗组28例和对照组46例,均随访6个月.比较两组患者随访期间残余蛋白尿下降率以及残余蛋白尿有效下降率的累积频率等....     

不同免疫吸附方法治疗系统性红斑狼疮的对比研究

目的比较A蛋白免疫吸附、PH350免疫吸附、DNA免疫吸附对系统性红斑狼疮的治疗效果。方法 98例系统性红斑狼疮患者,根据选择免疫吸附治疗的方式分为3组,观察治疗前后患者尿蛋白定量、血肌酐、尿素氮、白蛋白、免疫球蛋白、补体、自身抗体(抗核抗体、抗双链DNA抗体)、活动指数、器官功能等。结果治疗前后比较,患者尿蛋白定量、血肌酐、尿素氮、免疫球蛋白、自身抗体显著下降(均P0.05),其中A蛋白吸附与其他两种治疗方法免疫球蛋白清除率差异有统计学意义(均P0.05)。随观察时间的延长,不同方法的狼疮活动控制情况差异无统计学意义(P0.05)。结论不同免疫吸附治疗方法均可对系统性红斑狼疮取得较好的病情控制效果,但A蛋白对自身抗体清除更彻底。在临床实践中应综合考虑,选择最佳治疗方案。     

Differential response of urinary N-acetyl-beta-D-glucosaminidase to two osmotic diuretics in the dog

Urinary N-acetyl-beta-D-glucosaminidase (NAG), a lysosomal hydrolase located the proximal tubule of the kidney, has been used as a marker for subtle renal injury. In humans and other animals with diabetes mellitus, urinary NAG activity has been shown to increase within 12 hours of the onset of hyperglycemia and glycosuria. Whether the rise in urinary NAG activity is in response to the hyperglycemia or to the osmotic diuresis associated with glycosuria is not known, nor has the time course of the rise in enzyme activity been determined. A study was designed using four groups of dogs to examine these possibilities: group 1 (n = 5), control dogs; group 2 (n = 5), mannitol-infused dogs; group 3 (n = 5), low-glucose dogs; and group 4 (n = 5), high-glucose dogs. In groups 2 and 4, mannitol and glucose, respectively, were infused at a rate to double urine flow from the left ureter without altering the contralateral urine volume. In group 3, sufficient glucose was infused to elevate left renal vein glucose level without producing glycosuria. In the control dogs infused with normal saline solution at a constant rate throughout the control and study periods, no differences were found in urinary NAG excretion when data from individual clearance periods were compared for the right and left kidneys. In the low-glucose dogs, urinary NAG/creatinine ratios were significantly increased (P less than 0.01) when the left and right kidneys were compared for the duration of the infusion.(ABSTRACT TRUNCATED AT 250 WORDS)