N-acetyl-beta-D-glucosaminidase Index Research Articles

Side effects of long-term antiepileptic drugs on renal tubules of Indonesian children

Background Long-term treatment with antiepileptic drugs such as valproic acid (VPA) and carbamazepine (CBZ) may disrupt renal tubular function. Urinary N-acetyl-beta-D-glucosaminidase (NAG) may reflect tubular function and may be useful in detecting early-stage tubular injury. To date, no study has investigated the toxic effect of VPA and CBZ on renal tubules using urinary NAG in Indonesian children.
 Objectives To determine the toxicity of long-term VPA and/or CBZ treatment on renal tubules in children with epilepsy by measuring urinary NAG index (iNAG).
 Methods This cross-sectional study was conducted from January to March 2015 at Cipto Mangunkusumo Hospital and Anakku Clinic Pondok Pinang, Jakarta. We included children aged 3 to 16 years with epilepsy on VPA (n=36), CBZ (n=14), or VPA-CBZ combination (n=14) therapy. We measured urinary levels of creatinine and NAG. The urinary NAG reference value was obtained from age-matched healthy controls (n=30). To eliminate diurnal variations in NAG, iNAG was calculated by dividing urinary NAG by urinary creatinine. A urinary iNAG of more than two standard deviations above the mean for healthy children was considered elevated.
 Results Mean urinary iNAG values for the control, VPA, CBZ, and combination groups were 3.01, 5.9, 4.07, and 6.9 U/g, respectively. All treated groups had higher mean urinary iNAG values compared to the control group. Urinary iNAG was increased in 11/36 children on VPA, 2/14 children on CBZ, and 9/14 children on combination therapy.
 Conclusion Long-term VPA use may impair renal tubular function, as shown by the increased urinary iNAG. Combination therapy increases damage in the renal tubules.

Urinary N-acetyl-beta-D-glucosaminidase as an early marker for acute kidney injury in full-term newborns with neonatal hyperbilirubinemia.

Purpose. To investigate renal function estimated by markers in full-term newborns with hyperbilirubinemia. Methods. A total of 332 full-term newborns with hyperbilirubinemia and 60 healthy full-term newborns were enrolled. Total serum bilirubin, serum creatinine (Cr), serum blood urea nitrogen (BUN), serum cystatin C (Cys-C), urinary beta-2-microglobulin (β 2MG) index, and urinary N-acetyl-beta-D-glucosaminidase (NAG) index were measured before and after treatment. All newborns were divided into three groups according to total serum bilirubin levels: group 1 (221-256), group 2 (256-342), and group 3 (>342). Results. The control group and group 1 did not differ significantly in regard to serum Cr, serum BUN, serum Cys-C, urinary β 2MG index, and urinary NAG index. Urinary NAG index in group 2 was significantly higher than that in control group (P < 0.001). Between control group and group 3, serum Cys-C, urinary β 2MG index, and urinary NAG index differed significantly. The significant positive correlation between total serum bilirubin and urinary NAG index was found in newborns when total serum bilirubin level was more than 272 μmol/L. Conclusions. High unconjugated bilirubin could result in acute kidney injury in full-term newborns. Urinary NAG might be the suitable marker for predicting acute kidney injury in full-term newborns with hyperbilirubinemia.

Evaluation of Predictors of the Development of Azotemia in Cats

Chronic kidney disease (CKD) is a common condition in geriatric cats. Diagnosis is based on the development of persistent azotemia with inadequate urine concentrating ability. Biomarkers are sought for early identification. Clinical variables, urine concentrating ability, proteinuria, and N-acetyl-beta-D-glucosaminidase (NAG) index will be predictive of cats at risk of developing azotemia within 12 months. Client-owned nonazotemic geriatric (>or=9 years) cats. Prospective longitudinal cohort study monitoring a population of healthy nonazotemic geriatric cats every 6 months until development of azotemia, death, or the study end point (September 30, 2007). Multivariable logistic regression analysis was used to assess baseline clinical, biochemical, and urinalysis variables, urine protein to creatinine ratio (UP/C), urine albumin to creatinine (UA/C) ratio, and urinary NAG index as predictors of development of azotemia. One hundred and eighteen cats were recruited with a median age of 13 years. Ninety-five cats (80.5%) had been followed or reached the study end point by 12 months of which 30.5% (29/95) developed azotemia. Age, systolic blood pressure, plasma creatinine concentration, urine specific gravity, UP/C, UA/C, and NAG index were significantly associated with development of azotemia in the univariable analysis (P<or=.05). However, in the multivariable analysis, only plasma creatinine concentration with either UP/C (Model 1) or UA/C (Model 2) remained significant. This study demonstrates a high incidence of azotemia in a population of previously healthy geriatric cats. Proteinuria at presentation was significantly associated with development of azotemia although causal association cannot be inferred. Evaluation of NAG index offered no additional benefit.

Urinary Excretion of N-acetyl-.BETA.-D-Glucosaminidase and Its Isoenzymes in Cats with Urinary Disease.

The present study was designed to assess the clinical usefulness of measurement of urinary N-acetyl-beta-D-glucosaminidase (NAG) activity and its isoenzymes in cats with urinary disease. Thirty-five healthy cats and 9 cats with renal disease were used. Furthermore, a 5-year-old female cat was administered a large amount of sulfonamide in order to induce acute renal failure, and urine samples were collected for the assay of NAG activity and its isoenzymes. Urinary NAG activity was measured using p-nitrophenyl N-acetyl-beta-D-glucosaminide, and expressed as units per gram of urinary creatinine (NAG index). Urinary NAG isoenzymes were assayed by use of the mini-column method and electrophoresis. The overall mean value of urinary NAG index in healthy cats was 1.6+/-1.5 U/g. Urinary NAG index varied from 6.2 to 35.5 U/g in cats with chronic renal failure. There was no significant correlation between BUN, serum creatinine concentration and urinary NAG index. In cats with feline lower urinary tract disease, normal values of urinary NAG index were observed. In the urine samples of healthy cats, the proportions of NAG isoenzyme A (NAG-A) and isoenzyme B (NAG-B) were 79.1+/-4.4% and 21.0+/-4.4%, respectively, as assayed by the mini-column method. In the assay of NAG isoenzymes by electrophoresis, the proportions of NAG-A and NAG-B in healthy cats were 66.6+/-5.8% and 33.4+/-5.8%, respectively. The proportion of NAG-B as measured by electrophoresis was significantly larger (p<0.05) than that obtained with the mini column method. A feline case of acute renal failure experimentally-induced by sulfonamide showed elevation of urinary NAG index, NAG-A and NAG-B after injection of sulfonamide. The increase in NAG-B was larger than that of NAG-A. From the results reported here, measurement of urinary NAG and its isoenzymes seems to yield information about tubular damage at an early stage in cats with urinary disease.

Effect of age on urinary excretion of N-acetyl-beta-D-glucosaminidase.

To examine the relationship between the concentrations of urinary NAG and age, we measured ratios of urinary N-acetyl-beta-D-glucosaminidase (NAG) to urinary creatinine (NAG index) in 137 healthy subjects, aged from 19 to 88 years. The study is also designed to evaluate the relationship between urinary NAG and blood pressure. The subjects were divided into 7 subgroups, according to their age (< 30, 30-39, 40-49, 50-59, 60-69, 70-79, 80 or more years). There was a positive correlation between NAG index and age (r = 0.36; P < 0.001). The regression equation relating NAG index (y) to age (x) was y = 0.065x + 0.97. The mean NAG indexes for the 7 subgroups divided by age were significantly different (P < 0.01). There was a positive correlation between NAG index and systolic blood pressure (r = 0.18; P < 0.05), but was not between diastolic blood pressure and NAG index. In multiple regression analysis, age and BUN significantly correlated with NAG index (r = 0.32; P < 0.01, r = 3.3; P = 0.07, respectively), although there was no correlation between systolic blood pressure and NAG index. This cross-sectional study showed a clear elevation in NAG index with age. The rate of elevation was 0.65 per decade. Urinary excretion of NAG may be unrelated to blood pressure.

Microalbumin and N-acetyl-beta-D-glucosaminidase in random spot urine samples as predictors of diabetic nephropathy in the elderly non-insulin dependent diabetic patients

To determine whether urinary albumin to creatinine ratio (Albumin index) and urinary N-acetyl-beta-D-glucosaminidase (NAG) to creatinine ratio (NAG index) in random spot urine samples can be sued to predict the early stage of diabetic nephropathy in the elderly non-insulin dependent diabetic patients, we measured these concentrations in 150 non-diabetics, 61 diabetics without retinopathy and 56 diabetics with retinopathy. All patients with Albustix-positive urine were excluded. Subjects divided into two groups according to whether they were < 60 years (adult group) or > or = 60 years old (old group). Multiple regression analysis was used to investigate the relationship between NAG index or Albumin index (dependent variable) and independent variables (age, systolic blood pressure, duration of diabetes. HbA1c) in diabetic patients. Diabetic patients with retinopathy showed the highest mean Albumin index, followed by diabetic patients without retinopathy and then non-diabetic patients both in adult group and in old group (p < 0.001, p < 0.001, respectively). Diabetic patients with retinopathy showed the highest mean NAG index, followed by diabetic patients without retinopathy and then non-diabetic patients both in adult group and in old group (p < 0.001, p < 0.001, respectively). Albumin index positively correlated with systolic blood pressure, duration of diabetes and HbA1c (r = 0.18, r = 0.35, r = 0.18, respectively). NAG index positively correlated with age, duration of diabetes and HbA1c (r = 0.18, r = 0.25, r = 0.29, respectively). These results suggest that both NAG index and Albumin index in random spot urine samples may serve as early functional indicators of diabetic nephropathy in elderly diabetics.

Change of renal function during vancomycin therapy in extremely low birthweight infants.

Twenty extremely low birthweight infants were treated with vancomycin (VCM). Their gestational age was 26.3 +/- 1.4 weeks (range 24.0-28.7 weeks) and their birthweight was 829 +/- 133 g (range 562-900 g). At the time of initial administration of VCM, postnatal age was 29.5 +/- 15.8 days (range 5-54 days). Vancomycin was administered in a dose between 9.3 and 11.0 mg/kg every 12 h for a period of 6.3 +/- 2.4 days (range 4-13 days). Serum and urinary specimens were obtained before and after (within 24 h following the last dose) VCM therapy. Serum creatinine and sodium, and urinary N-acetyl-beta-D-glucosaminidase (NAG) activity, creatinine, sodium, and beta-2-microglobulin (BMG) concentrations were measured. Fractional excretion of sodium (FENa) and NAG index (NAG:creatinine ratio) were calculated. There were no significant differences between the before and after VCM treatment in serum creatinine, urinary BMG concentration, FENa and NAG index. No infant showed any symptoms of renal insufficiency. However, the NAG index and FENa increased after treatment in 1 of 20 infants. Vancomycin is effective and safe in the treatment of serious infections in extremely low birthweight infants.

The effects of massive transfusion and haptoglobin therapy on hemolysis in trauma patients.

A retrospective study was conducted on 53 patients who suffered severe trauma to determine the severity of intravascular hemolysis, the variations of renal function after trauma, and the effects of transfusion and haptoglobin therapy on these factors. Serum total haptoglobin, total hemoglobin, and urine free hemoglobin were measured 0, 1, 3, and 5 days after the trauma and renal tubular function was evaluated by the urinary N-acetyl-beta-D-glucosaminidase (NAG) index. Patients were divided into two groups depending on whether or not haptoglobin was given: group A (n = 34) did not receive haptoglobin, and group B (n = 19) was administered 4,421 +/- 245 U haptoglobin based on clinical indications. The total transfusion volumes were 3,477 +/- 594 ml and 10,146 +/- 1,794 ml, in groups A and B, respectively (P < 0.01). In group A, total haptoglobin was remarkably decreased to 69.4 +/- 11.6 mg/dl on day 0, but recovered to within the normal range on day 3, while the total hemoglobin was increased and the urine hemoglobin was positive in 61.8% of the patients. In group B, decreases in total haptoglobin and increases in total hemoglobin were more remarkable, and 84.2% had a positive urine hemoglobin. On day 5, groups A and B had NAG indices of 18.8 +/- 3.3 and 133.6 +/- 33.8 U/L/creatinine respectively (P < 0.01). These findings led us to conclude that trauma caused hemolysis and that the administration of 4,000 U haptoglobin did not improve either the severity of hemolysis or the deteriorated renal tubular function caused by massive transfusion.

Characterization of renal tubular damage in preterm infants with renal failure.

This study attempts to clarify the characteristics of renal tubular damage in preterm infants with renal failure. Sixty-one neonates (17 term and 44 preterm infants) were divided into three groups: 15 infants with intrinsic renal failure (IRF), five term and 10 preterm; 19 with pre-renal renal failure (PRF), five term and 14 preterm; and 27 without renal dysfunction (control), seven term and 20 preterm. Urine was collected for an 8 h period on the 2nd or 3rd day of life to determine the following parameters: creatinine clearance (Ccr), fractional excretion of sodium (FENa), urinary N-acetyl-beta-D-glucosaminidase (NAG) index and endothelin-1 (ET-1) excretion. Parameters of renal tubular function and/or renal tubular damage such as FENa, NAG index and ET-1 excretion were considered as a useful marker to differentiate IRF from PRF in preterm infants. However, these parameters were significantly elevated in preterm infants with PRF. These findings led us to make the following speculations: (i) renal tubular damage may easily occur in preterm infants; and (ii) there still remains difficulty in differentiation between IRF and PRF using Ccr instead of the fluid challenge test.

Urinary N-acetyl-beta-D-glucosaminidase activity in workers exposed to inorganic lead.

Urinary N-acetyl-beta-D-glucosaminidase (NAG) had been shown to be a useful early marker of renal injury. In workers exposed to lead it seems to be the only early marker but the dose response and dose effect relations are weak. Furthermore, the significance and underlying mechanism of increased urinary NAG activity is far from clear. By studying the isoenzyme profiles of urinary NAG, the significance and underlying mechanism may be further clarified. The heat labile (NAG-A) and heat stable (NAG-B) isoenzyme profiles of 128 workers exposed to lead from a lead stabiliser factory were analysed. NAG activity was expressed as total NAG, NAG-A, and NAG-B activity as well as ratios (NAG-B/total NAG and NAG-B/NAG-A). Exposure indices included the recent concentration of blood lead (BPb), a cumulative blood lead index (TBPb), and the recent change in concentration of blood lead (CBPb). The NAG indices correlated best with CBPb. Nearly 50% of the variation in NAG-B activity could be explained by the combination of all three exposure indices but only the CBPb was highly significant. When these exposure indices were entered separately into the regression equation, CBPb accounted for 36.3% of the variation in NAG-B activity, 5.7% was accounted for by TBPb and 2.7% by BPb. There was also no dose-effect or dose-response relation between the NAG variables and BPb or TBPb groups. With CBPb, there were dose-effect and dose-response relations. With CBPb, there was an increase in NAG variables in the group with more than 25% increase in blood lead over the past six months. The increase in NAG activity in this study is likely to be due to a recent increase in concentration of blood lead and hence presumably a recent rise in renal burden of inorganic lead. This suggests that the increase in urinary NAG activity is a form of acute response to a sharp increase in renal burden of lead, rather than to a cumulative dose. Heat stable NAG is part of the lysosomal membrane and is present in the urine when there is breakdown of lysosomes. Our data therefore contradict suggestions that the increase in urinary NAG activity is due to exocytosis.