Urinary protein excretion in Type 2 diabetes with complications

This study examined the association between urinary markers of early diabetic nephropathy and non-renal diabetic complications in 946 patients with type 2 diabetes mellitus. The association with hypertension was also studied. Data on macrovascular complications (ischaemic heart disease, stroke, peripheral vascular disease) and microvascular complications (retinopathy, peripheral neuropathy) were obtained from case records and clinical examination. Urine samples collected were analysed for albumin, beta(2)-microglobulin, retinol-binding protein (RBP), and N-acetyl-beta-D-glucosaminidase (NAG). Results showed that urinary albumin, RBP and beta(2)-microglobulin levels were higher in patients with macro- and/or microvascular complications, compared to those without. NAG levels were higher only in patients with both types of complications. A higher proportion of patients with complications had abnormally raised urinary protein and enzyme levels, compared to those without. Patients with associated hypertension had higher urinary levels of albumin and beta(2)-microglobulin, regardless of whether complications were present or not. RBP excretion was, however, markedly higher only in patients with microvascular complications, whereas hypertension did not influence NAG excretion. Urine albumin and RBP excretion were predictive of microvascular, as well as both macrovascular and microvascular complications, whereas NAG excretion was predictive of macro- and microvascular complications. These findings could mean that increased urinary protein and enzyme excretion were associated with more severe disease in these patients.     

Possible relationship between adiponectin and renal tubular injury in diabetic nephropathy

Adiponectin is an adipose-derived protein which has anti-inflammatory and anti-atherogenic properties in addition to insulin-sensitizing effects. To date, the role of adiponectin in the pathogenesis of diabetic nephropathy remains unclear. The aim of the present study was to explore the relationship between adiponectin and renal tubular injury in diabetic nephropathy. We determined serum and urinary adiponectin levels in type 2 diabetic patients with normoalbuminuria (n = 19), microalbuminuria (n = 18), and overt diabetic nephropathy (n = 16), and then analyzed the correlations between serum and urinary adiponectin, urinary N-acetylglucosaminidase (NAG) as a clinical marker of renal tubular injury, urinary monocyte chemoattractant protein-1 (MCP-1) as an inflammatory marker in renal tubulointerstitium, and clinical markers of renal disease. Notably, serum and urinary adiponectin levels were significantly increased in patients with overt diabetic nephropathy compared to those with normoalbuminuria and microalbuminuria. In univariate linear regression analysis, serum adiponectin levels were positively correlated with serum creatinine (r = 0.648, P<0.0001), urinary albumin (r = 0.583, P<0.0001), urinary NAG (r = 0.406, P<0.01), urinary MCP-1 (r = 0.514, P<0.0001), and urinary adiponectin (r = 0.691, P<0.0001) levels in all diabetic patients. Urinary adiponectin levels were also positively correlated with serum creatinine (r = 0.729, P<0.0001), urinary albumin (r = 0.799, P<0.0001), urinary NAG (r = 0.701, P<0.0001), and urinary MCP-1 (r = 0.801, P<0.0001) levels in all diabetic patients. Multiple linear regression analysis showed that serum creatinine and urinary adiponectin levels were independently associated with serum adiponectin levels (r(2) = 0.522), and that serum creatinine, urinary NAG, urinary MCP-1, and serum adiponectin levels were independent determinants of urinary adiponectin levels (r(2) = 0.851). These results collectively indicate that renal insufficiency and tubular injury possibly play a contributory role in increases in serum and urinary adiponectin levels in overt diabetic nephropathy. We presume that an increase in circulating adiponectin in overt diabetic nephropathy might be a physiological response to mitigate renal tubular injury and to prevent the further progression of diabetic nephropathy through its anti-inflammatory and anti-atherogenic effects.     

Contribution of hyperglycemia and renal damage to urinary C-peptide clearance in non-insulin-dependent diabetic patients.

The variation of urinary C-peptide clearance in relation to hyperglycemia and renal damage was evaluated in 57 patients with non-insulin-dependent diabetes mellitus (NIDDM) with and without overt proteinuria, 14 nondiabetic patients with renal disease (RD) and 18 healthy control subjects. Urinary C-peptide clearance expressed as the ratio of urinary C-peptide to creatinine clearance (CCP/CCR) in the fasting state did not differ in control subjects and RD patients, and was higher equally in NIDDM patients with and without proteinuria. In NIDDM patients without overt proteinuria, urinary levels of C-peptide, beta 2-microglobulin (B2M), N-acetyl-beta-D-glucosaminidase (NAG) and albumin as well as CCP/CCR ratio all decreased significantly with short-term glycemic control (P less than 0.05). Despite a wide range of CCP/CCR ratio (0.07-0.73), a weak but significant correlation (r = 0.56, P less than 0.005) was found between fasting serum and urinary C-peptide levels in NIDDM patients. These results suggest that urinary C-peptide may easily be affected by hyperglycemia per se rather than renal damage, while urinary B2M, NAG and albumin may be affected by both hyperglycemia and renal damage. When the urinary C-peptide level is interpreted, the influence of hyperglycemia on it must be taken into consideration.     

不同尿白蛋白水平的糖尿病患者单核细胞趋化蛋白-1和尿N-乙酰β-D-氨基葡萄糖苷酶的含量变化及其临床意义

目的观察不同尿白蛋白水平的糖尿病患者单核细胞趋化蛋白1(MCP1)和尿N乙酰βD氨基葡萄糖苷酶(NAG)的含量变化及其临床意义。方法将60例糖尿病患者按尿白蛋白排泄率(UAER)的不同分为正常白蛋白尿组、微量白蛋白尿组和大量白蛋白尿组3组。分别测定血清和尿MCP1的含量、尿NAG含量以及血肌酐(Scr)、糖化血红蛋白(GHbAlc),进行组间比较,并与对照组比较,同时做尿MCP1与GHbAlc、UAER、NAG的相关分析。结果尿MCP1含量及NAG含量在所有患者中均升高,明显高于对照组,且大量白蛋白尿组升高最明显,其升高程度与尿白蛋白排泄率增高程度一致,即随糖尿病肾病加重而逐渐升高。而血清MCP1水平较低,与对照组比较无显著性差异;尿MCP1与GHbAlc、UAER、NAG呈正相关关系。结论尿中MCP1升高与糖尿病肾病的发生发展有密切关系,尤其与肾小管间质损伤有更密切的关系。     

Urinary excretion of beta-thromboglobulin and N-acetyl-beta-D-glucosaminidase in type 1 diabetes: potential indicators of early nephropathy?

While microalbuminuria indicates the glomerular damage of early diabetic nephropathy, tubular abnormalities also occur at an early stage of diabetic renal disease. Urinary excretion of beta-thromboglobulin (BTG) and N-acetyl-beta-D-glucosaminidase (NAG) was measured in 132 normotensive Type 1 (insulin-dependent) diabetic patients with no evidence of overt renal disease, of whom 35 had microalbuminuria and the remainder had normal urinary albumin excretion. Of 21 patients in whom there was a detectable urinary BTG concentration, only 8 (38%) had a concurrently abnormal urinary albumin excretion. NAG excretion was elevated in 22 (63%) of the 35 patients with microalbuminuria; significant associations were also identified between urinary NAG excretion and smoking habit (x2 = 12.7, p less than 0.001) and glycated haemoglobin (r = 0.49, p less than 0.01). It is concluded that measurement of urinary BTG is not of sufficient sensitivity to be of value in the detection of early diabetic renal disease, but measurement of urinary NAG may be of value in the detection of diabetic nephropathy at a potentially reversible stage.     

膜性肾病患者尿蛋白成分与临床及病理的相关性分析

目的 探讨膜性肾病（MN）患者尿中N-乙酰-β-D-氨基葡萄糖苷酶（NAG）、视黄醇结合蛋白（RBP）、白蛋白（ALB）、免疫球蛋白G（IgG）、补体C3的构成特点及其与临床和病理的关系.方法 收集原发性膜性肾病患者95例,测定患者尿液中NAG、RBP、ALB、IgG及C3的浓度,并与各项临床及病理指标进行统计分析.结果 51 ～ 70岁年龄组患者尿RBP、IgG及C3含量较14～ 20岁组明显升高（P＜0.05）.血压升高组较血压正常组各种尿蛋白成分浓度均明显升高（P＜0.05）.肾功能不全组患者的尿NAG、RBP、ALB及IgG及补体C3水平均高于肾功能正常组（P＜0.05）.伴镜下血尿组患者尿RBP、ALB及IgG较不伴镜下血尿组明显增高（P＜0.05）.随着病理分期进展,患者尿NAG、RBP、IgG和C3等浓度明显升高（P＜0.05）;随着小管间质损害的加重,尿NAG、IgG和C3浓度均明显升高（P＜0.05）.结论 膜性肾病患者尿NAG、RBP、ALB、IgG及C3检测可以反映患者的病情,提示肾脏病理损害程度.     

老年糖尿病前期患者早期肾功能的变化

目的探讨老年糖尿病前期有无早期糖尿病肾病的改变。方法根据OGTT结果将68名老年人分为正常糖耐量（NGT）组和糖调节受损（IGR）组。测定尿微量白蛋白（mAlb）、转铁蛋白（TBF）、N-乙酰-B-D氨基葡萄糖苷酶（NAG）及视黄醇结合蛋白（RBP）。结果与TNG组比较，IGR组mAlb、NAG、RBP增高（P〈0．01）；IFG组RBP升高（P〈0．01）；IGT组四项指标均增高（P〈0．01）。糖负荷后2h血糖水平及血浆胰岛素水平与四种肾脏相关蛋白均有关联。结论老年糖尿病前期存在早期肾脏损害，并与血糖和胰岛素水平相关。     

Alteration of urinary sorbitol excretion in WBN-kob diabetic rats - treatment with an aldose reductase inhibitor

An accelerated polyol pathway in diabetes contributes to the development of diabetic complications. To elucidate diabetic nephropathy involving also renal tubular damage, we measured urinary sorbitol concentration concomitantly with urinary N-acetyl-D-glucosaminidase (NAG) excretion in WBN-kob diabetic rats.Twenty-four-hour urinary sorbitol concentrations increased in the diabetic rats in parallel with whole blood sorbitol concentrations. An increase in 24-h urinary NAG excretion coincided with the elevated urinary sorbitol levels in the diabetic rats. The administration of epalrestat, an aldose reductase inhibitor, reduced the increased whole blood and urinary sorbitol concentrations and urinary NAG excretion concomitantly with renal aldose reductase inhibition in the diabetic rats.These results indicate that diabetic nephropathy involves distorted cell function of renal tubules, and that treatment with epalrestat may prevent at least the progress of the nephropathy.     

血管紧张素转化酶抑制剂对糖尿病肾病早期肾小管功能的保护作用研究

目的探讨血管紧张素转化酶抑制剂（ACEI）对肾小管功能的保护作用。方法选择142例2型糖尿病合并高血压的患者，按治疗方法不同分A组（降糖的同时口服ACEI类降压药）和B组（降糖的同时口服非ACEI类降压药），检测各组尿N-乙酰-β-葡萄糖苷酶（NAG）、视黄醇结合蛋白（RBP）、α1微球蛋白（α1-MG）、IV胶原（CIV）水平，并进行统计学分析。结果组尿微量白蛋白排泄明显低于B组（P〈0．05）；肾小管功能指标中尿RBP明显低于B组（P〈0．05），而NAG、α1—MG、CIV差异无显著性意义（P〉0．05）。结论ACEI能明显减少糖尿病肾病患者尿白蛋白的排泄，而且对糖尿病肾病患者的肾小管功能有保护作用，糖尿病患者应提前使用ACEI类降压药。     

Urinary N-acetyl-ß-D Glucosaminidase as a Surrogate Marker for Renal Function in Autosomal Dominant Polycystic Kidney Disease: 1 year Prospective Cohort Study

ABSTRACT: BACKGROUND: Renal failure is one of the most serious complications associated with autosomal dominant polycystic kidney disease (ADPKD). To date, early markers have failed to predict renal function deterioration at the early stages. This 1-year prospective study evaluated N-acetyl-beta-D-glucosaminidase (NAG) as a new surrogate marker for renal function in ADPKD. METHODS: A total of 270 patients were enrolled in the study, and we measured urinary NAG, beta2-microglobulin, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) prospectively for 1 year to compare their predictive values for renal function. RESULTS: Baseline urinary NAG/Cr was negatively correlated with estimated glomerular filtration rate (GFR) (r2 = 0.153, P < 0.001) and positively correlated with total kidney volume (TKV) (r2 = 0.113, P < 0.001). Among other biomarkers, urinary NAG/Cr better discriminated patients with decreased renal function from those with conserved renal function, showing the largest area under the curve (AUC 0.794). Immunohistochemical study revealed strong staining along the cyst-lining epithelial cells as well as the nearby compressed tubular epithelial cells. However, both single and repeated measurements of urinary NAG/Cr failed to predict renal function decline in 1 year. CONCLUSIONS: Urinary NAG/Cr may be a useful surrogate marker for renal function in ADPKD patients.     

Increased excretion of N-acetyl-beta-D-glucosaminidase and beta2-microglobulin in gestational week 30

BACKGROUND: Little is known about when the urinary excretion of a combination of N-acetyl-beta-D-glucosaminidase (NAG) and beta2-microglobulin (beta2MG) concentration [relative to creatinine (Cr)] reaches maximal values during uncomplicated normotensive pregnancy. This study was thus designed to analyze when urinary excretion of biochemical parameters was increased during normotensive pregnancy. METHODS: NAG, beta2MG, total protein, albumin, and Cr were simultaneously measured in random (untimed) midstream urine samples from 22 healthy nonpregnant women and from 82 normotensive pregnant women (22 in gestational week 20, 25 in week 30, and 35 in week 37). RESULTS: NAG/Cr and beta2MG/Cr ratios were significantly higher (P < 0.01-0.05) in the normotensive pregnant women in gestational week 30 than in the nonpregnant control subjects and normotensive pregnant women in gestational week 20. The NAG/Cr and beta2MG/Cr ratios showed maximal values in gestational week 30. The total protein/Cr ratio was significantly higher in gestational weeks 20, 30, and 37 than in the control subjects. The albumin/Cr ratio was significantly higher in women in gestational week 30 and 37 than in women in gestational week 20 and in the control subjects. CONCLUSIONS: The excretion of both NAG and beta2MG relative to Cr was increased and showed the maximal values in gestational week 30 during normotensive pregnancy. The increase in a tubular enzyme (NAG) might be caused by renal tubular damage, and that in a low molecular weight protein (beta2MG) might result from decreased renal tubular reabsorption. These findings suggest that renal tubular damage and reabsorption dysfunction were increased in gestational week 30.     

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.     

Urinary angiotensin-converting enzyme activity in type 2 diabetes mellitus: its relationship to diabetic nephropathy

Urinary angiotensin-converting enzyme (ACE) and urinaryN-acetyl--d-glucosaminidase (NAG) were measured after a 5-year interval in 38 non-azotemic type 2 diabetic patients. Of these patients at baseline, 16 had nil nephropathy, 15 had incipient nephropathy, and 7 had overt nephropathy. During the follow-up, 6 and 1 of the 16 patients with nil nephropathy developed incipient and overt nephropathy, respectively. Four of the 15 patients with incipient nephropathy progressed to overt nephropathy. The 7 patients with overt nephropathy continued to have overt nephropathy, with slight azotemia in one. Urinary ACE and NAG levels were normal at baseline and showed no significant elevations at follow-up in the patients with nil nephropathy, no significant changes at baseline and modest elevations at follow-up in the patients with incipient nephropathy, and high at baseline and marked elevations at follow-up in the patients with overt nephropathy. In all patients, urinary ACE during the follow-up was positively correlated with urinary albumin or NAG, but not with glomerular filtration rate. Urinary ACE may be of poor prognostic value for the follow-up of diabetic patients, which is at variance with urinary albumin.     

Correlation between urinary activity of N-acetyl-β-d-glucosaminidase (NAG) and albumin excretion rate in type II (non-insulin-dependent) diabetic subjects

Summary Different kidney diseases are often associated with high urinary excretion of N-acetyl-β-D-glucosaminidase (NAG), a lysosomal enzyme involved in the breakdown of glycoproteins, whose activity is also increased in diabetic patients with poor metabolic control or vascular complications. In order to evaluate the relationship between renal function and urinary NAG levels in diabetes mellitus, 30 type II diabetic patients without evidence of kidney disease and 18 control subjects were studied. In each subject 24-h urinary excretion rates of NAG (fluorimetric method), albumin and β₂-microglobulin (radioimmunoassay), together with⁵¹Cr-EDTA clearance were performed. In diabetic patients urinary levels of NAG (356±25vs 162±9.2 nmol/h/mg creatinine, p<0.0001) and albumin (21±2.5vs 4.3±0.5 mg/24h, p<0.0001) were significantly higher than in the controls, while β₂-microglobulin levels and⁵¹Cr-EDTA clearance did not differ in the two groups. Moreover in diabetic patients NAG and albumin levels were positively and significantly correlated (r=0.63, p<0.001). These results suggest that urinary NAG excretion rate may be altered early in diabetic patients with apparently normal renal function; its diagnostic value seems to be similar to that of the albumin excretion rate.     

尿微量白蛋白、血清胱抑素C和β2微球蛋白联合检测对糖尿病肾病早期诊断的价值

目的:探讨尿微量白蛋白(mALB)、血清胱抑素C(CysC)和β2-微球蛋白(β2-MG)联合检测对糖尿病肾病早期诊断的价值。方法:根据尿微量白蛋白排泄率将115例2型糖尿病患者分为糖尿病无肾病组、糖尿病早期肾病组和糖尿病临床肾病组,45例健康体检人员为对照组;检测并比较4组mALB、血清CysC和β2-MG水平并进行相关分析。结果:糖尿病无肾病组尿mALB、血清CysC和β2-MG均明显高于对照组,差异有统计学意义(P0.05);糖尿病早期肾病组尿mALB、血清CysC和β2-MG均明显高于对照组和糖尿病无肾病组,差异有统计学意义(P0.05);糖尿病临床肾病组尿mALB、血清CysC和β2-MG均明显高于对照组、糖尿病无肾病组和糖尿病早期肾病组,差异有统计学意义(P0.05);3项指标联合检测的阳性率明显高于单项检测的阳性率;CysC和β2-MG与mALB呈正相关。结论:尿mALB、血清CysC和β2-MG都可作为糖尿病早期肾损害的敏感指标,联合检测对糖尿病肾病早期诊断具有重要的临床价值。     

Urinary N-acetyl-β-D-glucosaminidase activity predicts development of diabetic nephropathy

Background:   Urinary N-acetyl-β-D-glucosaminidase (NAG) has been suggested as a marker for diabetic nephropathy. A prospective study has therefore been performed to compare albuminuria and urinary NAG activities in type 2 diabetic patients.
Methods:   Forty-one patients (23 men and 18 women) with type 2 diabetes between 40 and 78 years of age were selected for a 5-year follow-up study. The urinary activities of NAG to creatinine ratios (NAG index) and albumin to creatinine ratios (albumin index) were measured in random spot urine samples. All patients were normoalbuminuric (albumin index < 30 mg/g Cr) at the beginning of the study. The mean NAG indexes and albumin indexes were calculated yearly.
Results:   During the observation period, 15 patients developed diabetic nephropathy (albumin index ≥ 30 mg/g Cr). Significantly higher mean NAG index and albumin index were found at the beginning of the study in patients who later developed diabetic nephropathy in comparison with those who did not (5.5 ± 2.0 vs 10.6 ± 4.2 U/g Cr, 11.0 ± 5.0 vs 17.8 ± 5.7 mg/g Cr, respectively). A gradual increase of the NAG index was found during the study in both patients who developed diabetic nephropathy and those who did not. On multiple logistic regression analysis, the NAG index at the beginning of the study was an independent predictor for the development of diabetic nephropathy.
Conclusions:   These results suggest that the NAG index may serve as an early functional indicator of diabetic nephropathy.     

尿白蛋白排泄率异常的2型糖尿病患者尿N-乙酰-β-葡萄糖苷酶、α1-微球蛋白及视黄醇结合蛋白检测的改变

目的检测不同尿白蛋白排泄率（UAER）的2型糖尿病（T2DM）患者尿N-乙酰-β葡萄糖苷酶（NAG）、α1-微球蛋白（α1-MG）、视黄醇结合蛋白（RBP）水平,探讨其对2型糖尿病早期肾损害诊断的应用价值。方法选择我院就诊的T2DM患者196例,健康体检者57名,检测12小时UAER水平。根据UAER水平将T2DM患者分为UAER正常组和异常组。分别检测尿NAG、α1-MG、RBP,肌酐（Cr）水平,并分析各组间差异。结果196例T2DM患者NAG／Cr、α1-MG／Cr及RBP／Cr水平较健康对照组明显升高（P〈0．05）;与对照组比较,T2DM患者中UAER正常组及异常组NAG／Cr、α1-MG／Cr及RBP／D水平具有显著性差异（P〈0．05或P〈0．01）。在T2DM患者中,UAER与NAG／Cr、α1-MG／Cr及RBP／Cr之间没有相关性,而NAG／Cr与α1-MG／Cr及RBP／Cr之间存在相关性（P〈0．01）。T2DM患者中UAER、NAG、劬MG、RBP联合检测阳性率高于各单-指标的检测阳性率（P〈70．05）。结论T2DM患者联合检测尿NAG、α1-MG、RBP可以提高糖尿病早期肾损害的诊断的敏感性,利于糖尿病肾病的早期预防。     

Clinical significance of determination of urinary albumin, beta 2 microglobulin and Tamm-Horsfall protein in diabetics

Twenty-four hour urinary albumin (Alb) beta 2 microglobulin (beta 2m) and Tamm-Horsfall protein (THP) were measured by radioimmunoassay in 69 diabetics and 23 normal controls. The excretion of urinary Alb, beta 2m and THP in the patients with diabetic nephropathy was found to be different from that of normal controls. The abnormality of excretion of Alb, beta 2m and THP is particularly evident in the patients with clinical diabetic nephropathy. These results indicate that the renal lesions of diabetes mellitus exist not only in the glomeruli but also in the proximal and/or distal tubules. There was a significantly positive correlation between THP excretion and creatinine clearance (less than 127 ml/min/1.73m2). The findings suggest that the excretion of urinary THP is a valuable index for evaluating the damages of nephrons. It is believed that determination of urinary Alb, beta 2m and THP in diabetics is beneficial to early detection of the sites and degree of the renal lesions.     

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.     

N-acetyl-beta-D-glucosaminidase urinary excretion as an early indicator of kidney dysfunction in rheumatoid arthritis patients on low-dose methotrexate treatment

The N-acetyl-beta-D-glucosaminidase (NAG) activities and albumin levels in the urine of 32 patients with active rheumatoid arthritis treated with low-dose pulse methotrexate (MTX) have been investigated. An increase in NAG urinary excretion was more frequent than the incidence of micro- or macroalbuminuria on entry, and during treatment with MTX. There was also a significant decrease in NAG levels observed at week 24. Parameters such as patient's age, time from onset, previous and current treatment did not allow us to predict the degree of NAG enzymuria. We conclude that MTX does not cause marked damage to renal proximal tubules; on the contrary, the observed significant decrease of urinary NAG on week 24 could be interpreted as a beneficial effect of MTX on kidney function. Early detection of high NAG enzymuria and elevated albumin levels in urine before the initiation of MTX therapy could be helpful in predicting possible MTX toxicity probably related to impaired renal clearance of MTX. Patients withdrawn from the study for non-renal-related adverse events also had an unusually large increase in urine NAG activity and urine albumin levels.