N-acetyl-β-glucosaminidase Research Articles

Effects of pentoxifylline administration on urinary N-acetyl-β-glucosaminidase excretion in type 2 diabetic patients: a short-term, prospective, randomized study

Background:Tubulointerstitial injury is a major feature of diabetic nephropathy and an important predictor of renal dysfunction. In 45 patients with type 2 diabetes mellitus (DM), we prospectively analyzed urinary excretion of N-acetyl-β-glucosaminidase (NAG), a marker of tubular renal damage; the potential relationship with urinary protein excretion; and effects of pentoxifylline (PTF) administration. Methods:Forty-five patients with type 2 DM initially were compared with 15 healthy controls matched for age and sex. After randomization, PTF (1,200 mg/d) was administered for 4 months to 30 patients and results were compared with data from a control group (n = 15). Results:Proteinuria and urinary NAG excretion were significantly greater in patients with DM with respect to healthy controls. Before PTF administration, baseline parameters were similar in both groups of patients with DM. At the end of the study, urinary protein excretion and NAG-creatinine ratios decreased in the active group from 920 ± 522 mg/d and 14.3 ± 16.9 U/g to 803 ± 523 mg/d (P < 0.001) and 10.5 ± 9.3 U/g (P < 0.05), respectively. Conversely, proteinuria and urinary NAG excretion did not change in the control group. Regression analysis showed that urinary NAG excretion was significantly associated with duration of DM (r = 0.61; P < 0.001) and proteinuria (r = 0.51; P < 0.001). Conclusion:Urinary NAG excretion is elevated in patients with type 2 DM compared with healthy individuals and increases as nephropathy progresses. PTF administration is effective in reducing proteinuria and urinary NAG excretion in these patients. These findings suggest that PTF may have beneficial effects on tubulointerstitial damage in diabetic kidney disease.

Comparison of laser-Doppler flowmetry with biochemical indicators of endothelial dysfunction related to early microangiopathy in Type 1 diabetic patients

The aim of this study was to compare biochemical markers of endothelial activation with microcirculation measured by laser-Doppler flowmetry in Type 1 diabetic patients with or without microangiopathy. A total of 44 Type 1 diabetic patients were subdivided into those with ( n=24) and without ( n=20) microangiopathy according to ophthalmological findings and the presence or absence of microalbuminuria. The control group consisted of 25 healthy people of comparable age, sex, and body mass index. Postocclusive reactive hyperemia (PORH) and thermal hyperemia (TH, at 44°C) were measured at the forearm. Serum N-acetyl-β-glucosaminidase (NAG) activity, serum E-selectin, and ICAM-1 concentrations were used as biochemical markers of endothelial dysfunction. A significantly lower velocity of perfusion increase during postocclusive hyperemia (PORH max· t 1 −1) and during thermal hyperemia (TH max· t 2 −1) ( P<.01) were accompanied by higher serum NAG activity (20.9±4.6 vs. 16.3±2.5 U l −1, P<.01) in diabetic patients with microangiopathy as compared to healthy persons. An inverse relationship was found between PORH max· t 1 −1 and NAG ( r=−.33) results in diabetic patients. In addition, higher mean values of serum NAG activity, E-selectin, and ICAM-1 concentrations were associated with significantly lower values of microcirculation parameters (PORH max· t 2 −1 and TH max· t 2 −1) in six patients without microangiopathy who had at least one of the above biochemical markers higher than mean+2 S.D. range. We suggest that serum NAG activity, E-selectin, and ICAM-1 concentrations may be used together with laser-Doppler flowmetry in Type 1 diabetic patients as early indicators of vascular changes in very early stage of diabetic microangiopathy.

Calculation of urinary enzyme excretion, with renal structure and function in dogs with pyometra

The urinary enzyme markers of renal damage, alkaline phosphatase (AP), γ-glutamyl transferase (GGT) and N-acetyl-β-glucosaminidase (NAG), glomerular filtration rate (GFR) and renal biopsies were studied to evaluate renal status in dogs with pyometra. After ovariohysterectomy, urinary enzymes were measured daily for 12 days in 55 dogs, and again at a later follow-up visit. Thirteen dogs had high levels of at least one enzyme at initial presentation. Seventeen dogs had a transient increase in urinary enzyme values between one and five days after surgery. Enzyme values usually declined to low activities within 12 post-operative days. Renal biopsies demonstrated tubular abnormalities in many dogs. Mean GFR was 2·4 and 2·0 ml min–1 kg–1, respectively on day 1 post-operatively and at the follow-up visit 1–4 months later. High urinary enzyme values often reflected extensive lesions in renal proximal tubular cells and sometimes reduced GFR.

Toxin synthesis and mucin breakdown are related to swarming phenomenon in Clostridium septicum.

Clostridium septicum is responsible for several diseases in humans and animals. The bacterium is capable of a simple kind of multicellular behavior known as swarming. In this investigation, environmental and physiologic factors affecting growth and swarm cell formation in C. septicum were studied over a range of dilution rates (D = 0.02 to 0.65 h(-1)) in glucose-limited, glucose-excess, and mucin-limited chemostats. Cellular differentiation was observed at low specific growth rates, irrespective of the carbon and energy source, showing that swarming occurred in response to nutrient depletion. Differential expression of virulence determinants was detected in swarm cells. Hemolysin was secreted by short motile rods but not swarm cells, whereas in cultures grown with glucose, only swarm cells formed DNase, hyaluronidase, and neuraminidase. However, neuraminidase and, to a lesser degree, hyaluronidase were induced in short motile rods in mucin-limited cultures. Both swarm cells and short rods were cytotoxic to Vero cells. Mucin was chemotaxic to C. septicum, and large amounts of mucin-degrading enzymes (beta-galactosidase, N-acetyl beta-glucosaminidase, glycosulfatase, and neuraminidase) were produced. Synthesis of these enzymes was catabolite regulated. In chemostat experiments, glycosulfatase secretion occurred only in swarm cells at low dilution rates in mucin-limited cultures. Determinations of oligosaccharide utilization demonstrated that N-acetylglucosamine, galactose, and N-acetylgalactosamine were the main carbon sources for C. septicum in mucin. Neuraminic acid was not assimilated, showing that neuraminidase does not have a direct nutritional function in this pathogen.

A preliminary investigation of the nephroprotective effects of the adenosine antagonist aminophylline in patients undergoing abdominal aortic aneurysm repair

Infra-renal clamping of the abdominal aorta during aneurysm repair is associated with a significant reduction in renal blood flow. Adenosine has been implicated as a mediator of renal ischemia in a number of human and animal models and its antagonism with theophylline has lead to the attenuation of these effects. In order to investigate the possible attenuation of renal arterial vasoconstriction associated with infrarenal cross clamping of the aorta we prospectively randomised 8 consecutive patients undergoing abdominal aortic aneurysm repair to receive aminophylline 5 mg/kg (n = 5) in 500 ml normal saline or placebo (n = 3) on the morning of surgery followed by an infusion of 6 mg/hour of aminophylline or placebo for 24 hours. Staff, investigators and patients were blinded. Inulin clearance as an indicator of glomerular filtration rate (GFR) was measured pre-operatively and again on the 2nd post-operative day. N-Acetyl-β-glucosaminidase (NAG) activity (mmol PNP/hour/mol creat) and Retinol Binding Protein (RBP) excretion (mg/mol creat) were measured to assess renal tubular damage and albumin excretion (mg/mol creat) as a marker of glomerular injury.

Relationship of N-Acetyl-β- Glucosaminidase Levels to Seriousness of Suicide Attempts

We hypothesized that levels of N-acetyl-β-glucosaminidase (NAG) would differ between patients making serious versus nonserious suicide attempts. The levels of NAG from 11 patients hospitalized for serious suicide attempts were compared to 5 patients whose suicide attempts were not rated serious. There was a significant difference in the mean NAG levels of the serious suicide attempters and the nonserious attempters (23 versus 52; p = 0.01). NAG may be a marker for a biological variable that is associated with the seriousness of a suicide attempt.

Polymorphonuclear elastase as a diagnostic marker of acute pyelonephritis in children.

Experimental evidence suggests that neutrophils and their metabolites play an important role in the pathogenesis of pyelonephritis. The aim of this study was to investigate the diagnostic value of polymorphonuclear elastase-a(1)-antitrypsin complex (E-a(1)-Pi) for the detection of acute pyelonephritis in children. Eighty-three patients, 29 boys and 54 girls, 25 days to 14 years of age, with first-time symptomatic urinary tract infection were prospectively studied. Fifty-seven healthy children served as controls. Dimercaptosuccinic acid (DMSA) scan and voiding cystourethrography were performed in all patients. Plasma and urinary E-a(1)-Pi, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), neutrophil count, urinary N-acetyl-beta-glucosaminidase (NAG), N-acetyl-beta-glucosaminidase b (NAG b), and creatinine levels were measured in all patients on admission and 3 days after the introduction of antibiotics. The same markers were also measured in the control subjects. Planar DMSA scintigraphy demonstrated changes of acute pyelonephritis in 30 of 83 children (group A). It was normal in the remaining 53 children (group B). The sex and age distributions were not significantly different between the 2 groups, as well as between the patients and the control subjects (group C). Nineteen of the 53 children with a normal DMSA had body temperature >/=38 degrees C, whereas all but 4 children with abnormal DMSA had temperature >/=38 degrees C. Therefore, the temperature was significantly different between these 2 groups. The sensitivity and specificity of fever (>/=38 degrees C) as an indicator of renal involvement based on isotopic findings were 86% and 64%, respectively. Given the significant number of the febrile children with normal DMSA scintiscans, group B was subdivided into B(1) with 19 febrile children (14 boys and 5 girls) and B(2) with 34 children whose body temperature was below 38 degrees C (8 boys and 26 girls). The sex and age distribution was significantly different between groups B(1) and B(2). The mean age of group B(1) was.78 years (range: 28 days to 9 years; median:.25 years; standard deviation: 2.1). All but 1 child in this group were younger than 1 year of age. In contrast, in group B(2), there were only 4 infants, the remaining 30 children were older than 2.5 years (mean age: 6 years; median: 7 years; standard deviation: 3.5; range: 34 days to 12 years). The mean duration of fever before hospital admission was 2.8 days for group A and 1.8 days for group B(1). This difference was not statistically significant. Similarly, body temperature was not significantly different between these 2 groups. The distribution of plasma E-a(1)-Pi values was normal in the control subjects. The sensitivity and specificity of plasma E-a(1)-Pi, as an indicator of renal involvement, were 96% and 50%, respectively, taking the 95th percentile of the reference range as a cutoff value. However, considering as a cutoff value the level of 72 microg/dL (95th percentile of group B(2)), its sensitivity and specificity were 74% and 86%, respectively. Plasma E-a(1)-Pi levels were significantly elevated in group A compared with group B and in both groups, the plasma E-a(1)-Pi values were significantly higher than in the control subjects. A significant difference also was noticed between group A and each of the subgroups B(1) and B(2) and also between the subgroups themselves. Plasma E-a(1)-Pi concentrations correlated significantly with neutrophil count in groups A (r =.3), B (r =.4), and B(2) (r =.46), but the correlation was not significant in group B(1.) ESR levels showed, among the different groups, similar differences with those of E-a(1)-Pi values. Unlike E-a(1)-Pi, CRP levels were comparable between groups A and B(1), which both consisted of febrile children. Neutrophil count was not significantly different between subgroups B(1) and B(2). (ABSTRACT TRUNCATED)

An association of NAG levels and a mutation of the CCK gene in panic disorder patients

Levels of the enzyme N-acetyl-β-glucosaminidase (NAG) and a mutation of cholecystokinin (CCK) gene appear to be independently associated with panic disorder. We explored whether there was an association of NAG levels and a CCK mutation identified in a group of panic disorder patients. NAG was measured in 12 panic disorder patients who had a mutation of the CCK gene and 17 who did not. Urine for NAG was collected at baseline and after 3 and 6 weeks of treatment. NAG levels were lower at all three times in the patients that did not have the CCK mutation. The difference between the two groups was significant at week 6 ( P<0.02), and showed a trend toward a difference at baseline ( P<0.15).

Effects of chronic inhibition of ACE and AT1 receptors on glomerular injury in dahl salt-sensitive rats.

To elucidate the contribution of the renin-angiontensin system (RAS) to glomerular injury in salt-sensitive hypertension, we investigated the chronic effects of the angiotensin I-converting enzyme inhibitor cilazapril and the angiotensin II type 1-receptor antagonist (AT1a) TCV-116 in Dahl-Iwai rats. Dahl salt-sensitive (S) rats receiving 8% salt diet for 6 wk were simultaneously treated with cilazapril (n = 6), TCV-116 (n = 6), or saline (n = 14). The 8% salt diet markedly increased systolic blood pressure (SBP), urinary protein, and N-acetyl-beta-glucosaminidase (NAG) excretion compared with 0.3% salt-treated S (n = 6) or salt-resistant (n = 6) rats. Although neither cilazapril nor TCV-116 reduced the elevated SBP, TCV-116 significantly lowered urinary protein and NAG excretion. Histologically, 8% salt treatment in S rats induced progressive sclerotic and proliferative glomerular changes, which were ameliorated by both drugs. TCV-116 increased the glomerular diameter. Immunofluorescence demonstrated the increased level of type III collagen in the mesangium of 8% salt-treated S rats, which was completely reversed by TCV-116. Competitive RT-PCR of mRNA extracted from the glomeruli revealed that 8% salt treatment significantly increased the levels of proliferating cell nuclear antigen (PCNA) and platelet-derived growth factor B-chain and that TCV-116 significantly reduced the levels of PCNA and transforming growth factor-beta1 (TGF-beta1). Thus, although the chronic RAS-inhibition in salt-sensitive hypertension exerted a histologically renoprotective effect by both ways without lowering blood pressure, the RAS inhibition due to AT1a had more beneficial advantages of reducing proteinuria and attenuating the levels of glomerular TGF-beta1 and extracellular matrix.

Effects of OPC-21268, a vasopressin V1-receptor antagonist, on expression of growth factors from glomeruli in spontaneously hypertensive rats

To assess the chronic in vivo effects of OPC-21268, a vasopressin-V1 receptor antagonist, on renal injury, we investigated the mRNA expressions of platelet-derived growth factor (PDGF) B-chain, transforming growth factor (TGF)- β1 and proliferating cell nuclear antigen (PCNA) in the glomeruli of spontaneously hypertensive rats (SHR) treated with OPC-21268 for 3 weeks. SHR aged 10 weeks were given 2% NaCl in drinking water for 3 weeks. The OPC group was fed a 0.5% OPC-21268-containing diet for 3 weeks and the control group was given a normal diet. There were no significant changes in the time course of systolic blood pressure, heart rate, urine volume, or urinary sodium, protein and N-acetyl- β-glucosaminidase (NAG) excretion between the two groups. Serum electrolytes, protein and creatinine levels also did not differ between the groups. The mRNA expressions of PDGF B-chain, TGF- β1 and PCNA in the glomerulus were examined using reverse transcriptase-polymerase chain reaction (RT-PCR) methods. The mRNA expressions of PDGF B-chain and PCNA among these were significantly suppressed in the OPC group. No significant differences in renal histology including the organ weights were found between the two groups; however, the glomerular size tended to be enlarged in the OPC group. These findings suggest that chronic V1-receptor blockade directly inhibits the glomerular proliferative injury of salt-loaded SHR at the established hypertension stage.

Experimental study on effect of Cordyceps sinensis on renal protection, urinary enzymes and nephrotoxicity of cyclosporine a in rats

Objective: To explore the protective effect ofCordyceps sinensis (CS) on nephrotoxicity of cyclosporine A (CsA) and its mechanism.Methods: The renal function of isolated perfused rats was observed before and after three months treatment by CS.Results: CS could improve the renal function, increase the volume of urine, Na+ and K+ excretion and inulin clearance rate, and reduce the resistance of renal perfusion. It was found that the activities of urinary N-acetyl-β-glucosaminidase (NAG), γ-glutamyl transferase (γ-GT) and lactate dehydrogenase (LDH) were lower in the CS treatment group than those in the control group.Conclusion: CS could protect the kidney from damage against nephrotoxicity of CsA and improve the abnormality of renal hemodynamics.

Renal disease in lymphatic filariasis: evidence for tubular and glomerular disorders at various stages of the infection.

Brugia malayi-infected patients, endemic normals with high levels of specific antibodies and European controls were investigated for kidney disorders by noninvasive techniques. Groups of patients with filarial infections included asymptomatic, microfilaraemic cases (group 1), patients with filarial fever (group 2) and with obstructive filariasis (group 3). Several patients underwent a treatment course with diethylcarbamazine (DEC) when blood and urine samples were collected. Urine samples were investigated for proteinuria and analysed by SDS-PAGE to discriminate between proteinurias caused by tubular and glomerular disorders. In addition, urine levels of alpha-1 microglobulin, of the brush border antigen gp400 and of N-acetyl-beta-glucosaminidase (NAG) activity were determined as indicators of tubular disorders, the albumin content of the urines served as indicator of glomerular alterations. IgG rheuma factors were also determined in the serum as possible reasons for glomerulonephritis. Neither in the endemic normals nor in the European controls there was evidence for kidney disorders. Infected patients had significantly increased proteinuria compared to controls. There were no significant differences between the 3 groups of infected persons, although the mean protein levels were highest in cases with chronic disease and lowest in asymptomatic patients. Quantitative urine analyses and results of accompanying tests suggest predominantly tubular but generally relatively weak disorders in asymptomatic infections; abundant involvement of the kidney which involves both compartments of the organ in the course of filarial fever; and partly severe and probably chronically progredient kidney alterations, which predominantly affect the glomerula in symptomatic cases. IgG rheuma factors do not seem to play a role in filarial infection associated renal disease. DEC-treatment indeed did not significantly alter degree and character of the proteinuria, but relatively high albumin levels in the urine of treated persons yet suggest increased glomerular disorders in these cases. In conclusion, renal disease appears to be a common event in Brugia filariasis; involving both the tubular and glomerular compartment of the organ its pathogenesis is obviously complex and not only immune complex-mediated.

Association of levels of N-acetyl-beta-glucosaminidase with severity of psychiatric symptoms in panic disorder

Urinary levels of N-acetyl-β-glucosaminidase (NAG) were measured in 58 patients with panic disorder. NAG levels were found to be significantly related to the severity of 23 of 72 mood states, measured by the Profile of Mood States, which were grouped in three categories: hostility or irritability, sadness, and panic. A similar result was found in a previous study of bipolar patients. NAG levels were also related to scores on the Hamilton Rating Scale for Anxiety and the Sheehan Patient-Rated Anxiety Scale. It is speculated that NAG could be a marker for serotonin.

Clinical observation on diabetic nephropathy treated with alcohol extraction of Flos Abelmoschus manihot

Sixty-eight cases of Non-Insulin Dependent Diabetes Mellitus complicated with Nephropathy were randomly divided into two groups: the treated group, 35 cases treated with alcohol extraction of Flos A-belmoschus manihot, Gliclazide and Captopril Tablets; and the control group, 33 cases treated with Gliclazide and Captopril Tablets, over a period of 8 weeks. The total effective rate in the treated and control group were 83.87% and 31.03% respectively (P<0.01), urinary micro-albumin were 31.7 and 76.3mg/L (P<0.05), proteinuria were 0.41 and 0.77g/24hr (P<0.01), blood β-microglobulin were 3317.8 and 3473. 1 hg/ml (P<0.05), urinary β-microglobulin were 367.2 and 641.5ng/ml (P<0.01), urinary N-acetyl-β-glucosaminidase (NAG) were 26.3 and 66. 7u/L (P<0.01), plasma lipid peroxide (LPO) were 6.13 and 8.78 nmol/L (P<0. 05), and plasma superoxide anion were 8.36 and 10.42 kcpm respectively (P<0.05). It was suggested that alcohol extraction ofAbelmoschus manihot could eliminate oxygen free radicals, alleviate renal tubular-interstitial diseases, improve renal function, and reduce proteinuria.

Diltiazem minimizes tubular damage due to FK506-mediated nephrotoxicity following ischemia and reperfusion in rats

We examined the nephrotoxicity of tacrolimus (FK506) in a model of mild warm ischemia. After clamping of both renal arteries of male Sprague-Dawley rats for 20 min, the animals received tacrolimus (3 mg/kg/day i.p.), vehicle of a combination of tacrolimus (3 mg/kg/day i.p.) and diltiazem (12 mg/kg, orally) or vehicle and diltiazem (12 mg/kg, orally). The excretion of urinary enzymes was determined on a daily basis, creatinine clearance at day 10. Tacrolimus significantly increased NAG ( N-acetyl-β-glucosaminidase) excretion and associated histological damage, finally decreasing creatinine clearance. The toxic potential of tacrolimus was markedly enhanced by ischemia. The additional application of diltiazem reduced NAG excretion and histological damage without affecting creatinine clearance. Thus, the protective effect of diltiazme on tacrolimus-induced nephrotoxicity seems to be at least partially a tubular one.

Microbicidal mechanisms of liver macrophages in experimental visceral leishmaniasis.

To study the differential microbicidal potentials of liver macrophages, the oxygen-dependent and oxygen-independent pathways in Kupffer cells and immigrant macrophages of Leishmania donovani-infected BALB/c mice were investigated. Hydrogen peroxide assay was performed using horse radish peroxidase-dependent oxidation of phenol red to quantitate the reactive oxygen species produced. To examine the oxygen-independent pathway, the enzymes N-acetyl-beta-glucosaminidase (NAG) and beta-glucuronidase (beta G) were investigated after exposure of cells to lipopolysaccharide. Hydrogen peroxide release by Kupffer cells was significantly decreased only at 21 days postinfection, whereas hydrogen peroxide release by immigrant macrophages was significantly increased on all postinfection days with a maximum at 21 days postinfection. The pattern of release of NAG and beta G was similar in both cell populations with a peak at 21 days postinfection. The present study therefore suggests that Kupffer cells and immigrant macrophages adopt different pathways to cope with this infection.

Increased urinary N-acetyl-β-glucosaminidase (NAG) excretion in young insulin-dependent diabetic patients

We evaluated urinary N-acetyl-β-glucosaminidase (NAG) excretion in overnight and in second morning urine in 50 young diabetic patients, aged 7.4–25 years with a disease duration from 2–19.6 years. In all patients we evaluated urinary NAG and creatinine excretion, in both overnight and second morning urine, glycosuria, fasting blood glucose and HbA 1c levels, insulin requirement, blood pressure, and the presence of microangiopathic complications. Urinary NAG excretion was also evaluated in 69 age- and sex-matched controls. NAG was determined using 3-cresolsul-fonphtaleinyl-β- N-acetylglucosaminide as substrate (Boehringer Mannheim, Germany). In the diabetic patients NAG Cre ratios were significantly higher than in controls both in overnight and second morning urine ( P < 0.0005, respectively). We observed significantly higher NAG Cre ratio levels in the second morning than in overnight urine, both in controls and in diabetics ( P < 0.0005, respectively). Elevated (above 2 S.D. of the mean) NAG Cre ratios were found in NAG Cre patients (34%) in overnight urine and in 29 50 (58%) in second morning urine. No correlation was observed between NAG Cre ratio levels and age, duration of disease, pubertal stage, body mass index, fasting blood glucose, glycosuria, insulin requirement and blood pressure. The patients with one or more complications did show NAG Cre ratio levels significantly higher than those without complications ( P < 0.005) in second morning urine, but not in overnight urine. Our study has demonstrated an increased rate of urinary NAG excretion in young IDDM patients, in particular in those with microangiopathic complications.

Is carbamazepine associated with NAG elevations suggestive of renal disease?

Elevations of urinary N-acetyl-β-glucosaminidase (NAG) were found in previous studies of epileptic patients using carbamazepine. Since NAG can be a sensitive indicator of urinary tract problems, it was postulated that carbamazepine could be causing urinary tract damage. To explore this issue further, 27 mood disorder patients who were taking carbamazepine were compared to 171 mood disorder patients who were not using carbamazepine. There were no significant differences in NAG levels between the two groups. A hypothesis is presented which states that the elevated NAG levels found in some seizure patients could be associated with abnormalities of serotonin metabolism.

Urinary N-acetyl-beta-glucosaminidase activity in type I diabetes mellitus.

A commercial method for N-acetyl-beta-glucosaminidase (NAG) is described for use on a discrete analyser. Timed overnight urine was obtained from 20 healthy volunteers and 60 Type I diabetic patients for estimation of NAG (expressed in relation to creatinine) and albumin excretion rate (AER). The upper reference limit for NAG excretion in the control patients was found to be 0.25 U/mmol creatinine but was abnormally raised in 60% of Type I diabetic patients before any increase in AER (greater than 20 micrograms/min), and in 82% of patients with AER greater than 200 micrograms/min. A positive correlation was found between NAG excretion and AER in Type I diabetes (r = 0.61, p < 0.01), but not with glycaemic control as measured by serum fructosamine levels. We conclude that measurement of NAG excretion in diabetes indicates renal tubular dysfunction or damage before any significant change in albumin excretion rate.

Early changes of serum N-acetyl- β-glucosaminidase, tissue plasminogen activator and erythrocyte Superoxide dismutase in relation to retinopathy in type 1 diabetes mellitus

Biochemical markers of early changes that are characteristic for diabetic microangiopathy are not completely understood. We investigated activities of serum N-acetyl- β-glucosaminidase (NAG), tissue plasminogen activator and erythrocyte Superoxide dismutase in well defined groups of type 1 diabetic patients. Patients were selected on the basis of 4 year follow-up observation. Forty-two type 1 diabetic patients were subdivided into those without retinopathy (= 13) throughout the study, those with newly developed or worsened retinopathy (= 12) during 4 years and those with retinopathy already established at the beginning of the study and without evidence of its progression (= 17). All diabetic patients had albustix-negative urine. A significant increase of the mean serum NAG activity during 4 years was found only in patients without retinopathy ( P < 0.01) whereas no changes of the altered enzyme activities were present in patients with developing and established retinopathy. The mean activity of tissue plasminogen activator was elevated in all groups of diabetic patients compared with healthy subjects ( P < 0.001). A significant positive correlation was found between plasminogen activator and serum NAG (= 0.51, P < 0.01). Erythrocyte superoxide dismutase was higher in diabetic patients than in healthy persons ( P < 0.01) but no differences were observed between the patients with or without retinopathy. Superoxide dismutase positively correlated with NAG (= 0.57, P < 0.01). We conclude that early functional changes precede a morphological development of diabetic retinopathy as was evident from the altered enzyme activities.