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

Urinary N-Acetyl-Beta-D-Glucosaminidase levels predict immunoglobulin a nephropathy remission status

BackgroundTubulointerstitial lesions play a pivotal role in the progression of IgA nephropathy (IgAN). Elevated N-acetyl-beta-D-glucosaminidase (NAG) in urine is released from damaged proximal tubular epithelial cells (PTEC) and may serve as a biomarker of renal progression in diseases with tubulointerstitial involvement.MethodsWe evaluated the predictive value of urinary NAG (uNAG) for disease progression in 213 biopsy-proven primary IgAN patients from January 2018 to December 2019 at Zhongshan Hospital, Fudan University. We compared the results with those of serum cystatin C (sCysC).ResultsIncreased uNAG and sCysC levels were associated with worse clinical and histological manifestations. Only uNAG level was independently associated with remission status after adjustment. Patients with high uNAG levels (> 22.32 U/g Cr) had a 4.32-fold greater risk of disease progression. The combination of baseline uNAG and clinical data may achieve satisfactory risk prediction in IgAN patients with relatively preserved renal function (eGFR ≥ 60 ml/min/1.73 m2, area under the curve [AUC] 0.760).ConclusionOur results suggest that uNAG is a promising biomarker for predicting IgAN remission status.

Comparison of the Effects of Sodium Valproate and Carbamazepine on Renal Function in Children With Epilepsy

Background: Renal disorders have been observed with the long-term treatment of some antiepileptic drugs (AEDs). We aimed to compare the effects of carbamazepine (CBZ) and valproate (VPA) on renal function in children with epilepsy. Methods: This quasi-experimental study included children with epilepsy aged 2 months to 14 years who had persistently been receiving CBZ or VLP monotherapy for more than 6 months and were referred to Bandar Abbas Children’s Hospital, Bandar Abbas, Iran, 2019-2020. Demographic features, including age and sex, as well as family history of epilepsy, disease duration, and duration of treatment were recorded for each patient. Random blood and urine samples, along with 24-hour urine samples were collected from all the participants. Blood urea nitrogen (BUN), sodium, alkaline phosphatase (ALP), and pH were measured in blood samples. Glucose, protein, sodium, potassium, phosphorus, and creatinine were estimated in 24-hour urine samples. N-acetyl-beta-D-glucosaminidase (NAG) and pH were assessed in random urine samples. Results: Of the 80 children in this study with a mean age of 7.43±3.22 years, 58 (72.5%) were males. Children in both groups were comparable in terms of age, sex, family history of epilepsy, and disease and treatment duration. The urine NAG level was significantly higher in the VPA group compared to the CBZ group (P=0.010). Further, 24-hour urine protein and glucose levels were significantly higher in the VPA group. As for blood parameters, except for sodium (P=0.034), ALP (P<0.001), and pH (P=0.006) which were significantly higher in the CBZ group, other parameters were significantly higher in the VPA group. Conclusion: Overall, CBZ appears to be safer than VPA regarding its effects on renal function in children treated for epilepsy.

Sex-specific differences in early renal impairment associated with arsenic, lead, and cadmium exposure among young adults in Taiwan

Exposure to a single metal has been reported to damage renal function in humans. However, information regarding the association between multiple-metal exposure and markers for early renal impairment in different sexes among the young adult Taiwanese population is scarce. We assessed the association between exposure to arsenic (As), cadmium (Cd), and lead (Pb), and early renal impairment markers using urinary microalbumin (MA), β2-microglobulin (β2MG), and N-acetyl-beta-D-glucosaminidase (NAG) by analyzing 157 young adults aged 20‒29 years, in Taiwan. Inductively coupled plasma mass spectrometry was used to determine urinary As, Cd, and Pb levels. Regression models were applied to different sex groups. The results showed that after adjusting for potential confounding factors and each metal, urinary Cd levels were significantly positively associated with urinary MA (β = 0.523, 95% CI: 0.147–0.899) and β2MG (β = 1.502, 95% CI: 0.635–2.370) in males. However, the urinary Cd level was significantly positively associated with only urinary NAG (β = 0.161, 95% CI: 0.027–0.296) in females. This study thus indicates that the effect of exposure to metals (especially Cd) on early renal impairment among young adults in Taiwan is sex-specific. Our study results could contribute toward developing early intervention programs for decreasing the incidence of renal dysfunction. Further studies are warranted to confirm our findings and clarify the potential mechanisms involved.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11356-022-19521-3.

Role of urinary NAG enzyme in early detection of renal impairment in cystic fibrosis patients

BackgroundCystic fibrosis (CF) is the most common life-limiting autosomal recessive disease among people in the USA and Europe with increased prevalence in Egypt. Affected children are in danger of acute kidney injury and the development of chronic renal disease through exposure to multiple nephrotoxic agents. N-acetyl beta-D-glucosaminidase (NAG) is a lysosomal enzyme present in high concentrations in the proximal tubular cells, thus raising urinary NAG levels to reflect tubular dysfunction. The aim of our study is to detect the role of the urinary NAG enzyme in the early detection of renal impairment in CF patients. This cross-sectional study enrolled 40 CF patients diagnosed in the CF Clinic in Children’s Hospital of Cairo University. They were age- and sex-matched to 40 healthy controls. All patients had glomerular filtration rate (GFR), serum creatinine, blood urea nitrogen (BUN), albumin/creatinine (A/C) ratio measured, urine analysis, urinary NAG enzyme using enzyme-linked immunosorbent assay (ELISA), and renal ultrasound (U/S) were done.ResultsOur study showed high levels of urinary NAG in cases with a significant difference between cases and controls (P value < 0.001). There was a significant correlation between urinary NAG enzyme elevation and A/C ratio in urine, nephrotoxic drugs administration, and duration of disease (P value = 0.002, 0.005, 0.019), respectively.ConclusionOur study suggested that the NAG enzyme is a good early detector of renal impairment in CF patients before the conventional laboratory assays become deranged.

Distribution of urinary N-acetyl-beta-D-glucosaminidase and the establishment of reference intervals in healthy adults.

BackgroundUrinary N‐acetyl‐beta‐D‐glucosaminidase (NAG) plays an important role in the early diagnosis and progression of diseases related to renal tubular injury. We detected the urinary NAG concentration, assessed the preliminary statistics of its distribution, and established reference intervals for healthy adults in China using the rate method.MethodsA total of 1,095 reference individuals (aged 20 to 79 years) met the requirements for inclusion in this study. Urinary NAG concentrations were detected using an AU5800 automatic biochemical analyzer with its matched reagents. The Kolmogorov‐Smirnov test was used to analyze the normality of the data. According to the guidelines of C28‐A3 and WS/T 402‐2012, the reference intervals of urinary NAG were established using the nonparametric percentile method (unilateral 95th percentile).ResultsThe urinary NAG data showed a non‐normal distribution. The distribution of urinary NAG was significantly different by sex and age. Therefore, the reference intervals of urinary NAG were established using the rate method: males (aged 20–59 years) <19.4 U/L (90% CI: 18.0–20.3 U/L); males (aged 60–79 years) <22.3 U/L (90% CI: 20.2–22.6 U/L); females (aged 20–59 years) <15.7 U/L (90% CI: 15.2–16.5 U/L); and females (aged 60–79 years) <21.4 U/L (90% CI: 20.3–22.3 U/L).ConclusionsWe established preliminary reference intervals of urinary NAG for healthy adults in China to provide guidance for health screening, auxiliary diagnosis, and treatment monitoring of renal tubule‐related diseases.

Assessment of Subclinical Renal Glomerular and Tubular Dysfunction in Children with Beta Thalassemia Major.

Background: A good survival rate among patients with beta thalassemia major (beta-TM) has led to the appearance of an unrecognized renal disease. Therefore, we aimed to assess the role of serum cystatin-C as a promising marker for the detection of renal glomerular dysfunction and N-acetyl beta-D-glucosaminidase (NAG) and kidney injury molecule 1 (KIM-1) as potential markers for the detection of renal tubular injury in beta-TM children. Methods: This case-control study was implemented on 100 beta-TM children receiving regular blood transfusions and undergoing iron chelation therapy and 100 healthy children as a control group. Detailed histories of complete physical and clinical examinations were recorded. All subjected children underwent blood and urinary investigations. Results: There was a significant increase in serum cystatin-C (p < 0.001) and a significant decrease in eGFR in patients with beta-TM compared with controls (p = 0.01). There was a significant increase in urinary NAG, KIM-1, UNAG/Cr, and UKIM-1/Cr (p < 0.001) among thalassemic children, with a significant positive correlation between serum cystatin-C, NAG and KIM-1 as regards serum ferritin, creatinine, and urea among thalassemic patients. A negative correlation between serum cystatin-C and urinary markers with eGFR was noted. Conclusion: Serum cystatin-C is a good marker for detection of glomerular dysfunction. NAG and KIM-1 may have a predictive role in the detection of kidney injury in beta-TM children.

The association of blood lead levels and renal effects may be modified by genetic combinations of Metallothionein 1A 2A polymorphisms

Metallothionein (MT) is a protein with function of heavy metal detoxification. However, studies about how single nucleotide polymorphisms (SNPs) of MT genes influence lead nephropathy are relatively scarce. Therefore, our aim is to investigate the association between blood lead levels and renal biomarkers and to study whether this association is influenced by the combination of MT1A and MT2A SNPs. Blood lead, urinary uric acid (UA), and urinary N-acetyl-beta-d-glucosaminidase (NAG) levels were analyzed from 485 participants. Genotyping were performed on MT1A SNPs (rs11640851 and rs8052394) and MT2A SNPs (rs10636 and rs28366003). The combined MT1A 2A SNPs were divided into 16 groups. Among renal biomarkers, urinary UA was negatively significant associated with the time-weighted index of cumulative blood lead (TWICL), while urinary NAG was positively significant with TWICL. Furthermore, the association between urinary UA and TWICL was significantly modified by group 6 of combined SNPs (MT1A 2 A SNPs combination were AAAGGGAA, ACAGGGAA, and ACGGGGAA). In conclusion, the negative association of urinary UA and TWICL is modified by group 6, which means participants of group 6 are more susceptible to lead nephrotoxicity.

Urinary N-acetyl-beta-d-glucosaminidase (NAG) with neutrophil gelatinase-associated lipocalin (NGAL) improves the diagnostic value for proximal tubule damage in diabetic kidney disease

Screening for diabetic kidney disease (DKD) remains a challenge; however, there has been an ongoing research to investigate the diagnostic value of different biomarkers to identify DKD. The aim of this study was to assess the diagnostic value of both N-acetyl-beta-d-glucosaminidase (NAG) and neutrophil gelatinase-associated lipocalin (NGAL) in the progression of DKD. This cross-sectional case-control study included 92 type 2 diabetic patients with or without DKD. Urinary NAG and NGAL were measured to evaluate their diagnostic values as biochemical markers related to DKD. Both urinary NAG and NGAL levels were significantly higher among patients with DKD. In multiple linear regression analysis, NAG showed a positive significant association with NGAL in the three different adjusted models, while no significant correlation with fasting blood glucose, glycated hemoglobin, serum creatinine, estimated glomerular filtration rate, and albumin creatinine ratio were observed. The area under the curve for NGAL was 0.659 (p = 0.01) and 0.564 (p = 0.297) for NAG in DKD patients. This study demonstrates the association between urinary NAG and NGAL as a tubular damage marker for DKD although longitudinal studies are needed to evaluate its diagnostic value.

Urinary N-acetyl-beta-d-glucosaminidase levels in diabetic adults

Diabetes mellitus (DM) is known to be one of the most common causes of end-stage renal disease. The disease is usually not detected on time, because of the large functioning reserve of the kidney. Currently used markers (serum creatinine, creatinine clearance, urea, and electrolytes) remain relatively normal even when more than 50% of the renal nephron is not functioning. The aim of this study was to determine the level of urinary N-acetyl-beta-d-glucosaminidase (NAG) in diabetic adults in comparison with some currently used markers. A total of 56 diabetic patients between the ages of 23 and 63 were used for this study and 30 nondiabetic between the ages of 18 and 62 were used as control. The diabetic patients were classified into three groups based on how long they have been diagnosed: <2 years (25), 2–5 years (30), and >5 years (25). Spot midstream urine samples were collected into sterile containers, and blood samples were collected into plain tubes. All the analyses were done spectrophotometrically. Creatinine clearance was calculated using the Cockcroft–Gault Equation. There was a significant increase (P < 0.01) in NAG values of 2–5 years and above 5 years and control. The urinary microalbumin concentration of controls was significantly different (P < 0.05) only with those who have had DM for <2 years. Urinary creatinine concentration of control was significantly higher (P < 0.05) than values of all the diabetic groups. There was a significant increase (P < 0.01) in creatinine clearance of control group and those who have had DM for <2 years. It is thus concluded that urinary NAG can be used as an early marker in the diagnosis of diabetic nephropathy since urinary NAG increases first before the other markers analyzed in this current study begins to increase.

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.&#x0D; 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).&#x0D; 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.&#x0D; 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.&#x0D; 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.

Upregulation of PPAR-γ mediates the renoprotective effect of omega-3 PUFA and ferulic acid in gentamicin-intoxicated rats

Ferulic acid (FrA) is a natural product containing phenolic compounds. ω-3 PUFA is the major constituent of fish oil. The aim of this study was to investigate the renoprotective role of FrA and FO in gentamicin (GM)-induced nephrotoxicity in rats. Forty four male rats were divided equally into 4 groups: Control group, GM group, FrA + GM group and FO + GM group. Each of the treated groups was injected with GM (40 mg/kg) i.p. for 9 consecutive days. FrA (100 mg/kg) and FO (5 mL/kg) were given to rats orally daily for 10 days prior to GM and then concomitantly with GM for additional 9 days. Kidney function was assessed by serum BUN and creatinine, urinary albumin excretion and N-acetyl-beta-D-glucosaminidase (NAG) activity and histopathological examination. The anti-inflammatory property was evaluated by measuring renal resolvin E1 and gene expression of PPAR-γ. The antioxidant activity was indicated by renal catalase (CAT) activity. GM-induced nephrotoxicity was evidenced by the renal histopathological changes along with increased renal indices. Prior and concomitant treatment with FrA or FO ameliorated nephrotoxic effect of GM as indicated by the significant decrease of serum BUN and creatinine, urinary albumin excretion and urinary NAG activity. Both treatments significantly enhanced CAT activity and gene expression of PPAR-γ. Resolvin E1 was significantly elevated in FO but not in FrA group. FrA and FO proved anti-inflammatory and renoprotective effects, which could be through their PPAR-γ agonist activity. Because FrA and FO are natural products, they could provide a safe intervention strategy in cases of exposure to nephrotoxins.

Interaction of melamine and di-(2-ethylhexyl) phthalate exposure on markers of early renal damage in children: The 2011 Taiwan food scandal.

Melamine and phthalate, mainly di-(2-ethylhexyl) phthalate (DEHP), are ubiquitously present in the general environment. We investigated whether urine melamine levels can modify the relationship between DEHP exposure and markers of early renal damage in children. A nationwide health survey for Children aged ≤12 years possibly exposed to phthalates were enrolled between August 2012 and January 2013. They were administered questionnaires to collect details regarding past DEHP exposure to phthalate-tainted foodstuffs. Urine samples were measured melamine levels, phthalate metabolites and biomarkers of renal damage, including urine microalbumin/creatinine ratio (ACR), N-acetyl-beta-d-glucosaminidase (NAG), and β2-microglobulin. The study included 224 children who had a median urine melamine level (μg/mmol creatinine) of 1.61 ranging 0.18-47.42. Positive correlations were found between urine melamine levels and urine ACR as well as urine NAG levels (both Spearman correlation coefficients r = 0.24, n = 224, p < .001). The higher the past DEHP exposure or urine melamine levels, the higher the prevalence of microalbuminuria. An interaction effect was also found between urine melamine levels and past DEHP exposure on urine ACR. Melamine levels may further modify the effect of past DEHP exposure on urine ACR in children.

Acute Renal Graft-Versus-Host Disease in a Murine Model of Allogeneic Bone Marrow Transplantation

Acute kidney injury (AKI) is a very common complication after allogeneic bone marrow transplantation (BMT) and is associated with a poor prognosis. Generally, the kidneys are assumed to not be no direct targets of graft-versus-host disease (GvHD), and renal impairment is often attributed to several other factors occurring in the early phase after BMT. Our study aimed to prove the existence of renal GvHD in a fully major histocompatibility complex (MHC)-mismatched model of BALB/c mice conditioned and transplanted according to 2 different intensity protocols. Syngeneically transplanted and untreated animals served as controls. Four weeks after transplantation, allogeneic animals developed acute GvHD that was more pronounced in the high-intensity protocol (HIP) group than in the low-intensity protocol (LIP) group. Urea and creatinine as classic serum markers of renal function could not verify renal impairment 4 weeks after BMT. Creatinine levels were even reduced as a result of catabolic metabolism and loss of muscle mass due to acute GvHD. Proteinuria, albuminuria, and urinary N-acetyl-beta-d-glucosaminidase (NAG) levels were measured as additional renal markers before and after transplantation. Albuminuria and NAG were only significantly increased after allogeneic transplantation, correlating with disease severity between HIP and LIP animals. Histological investigations of the kidneys showed renal infiltration of T cells and macrophages with endarteriitis, interstitial nephritis, tubulitis, and glomerulitis. T cells consisted of CD4+, CD8+, and FoxP3+ cells. Renal expression analysis of allogeneic animals showed increases in indoleamine-2,3 dioxygenase (IDO), different cytokines (tumor necrosis factor α, interferon-γ, interleukin 1 α [IL-1α], IL-2, IL-6, and IL-10), and adhesion molecules (intercellular adhesion molecule 1 and vascular cell adhesion molecule 1), resembling findings from other tissues in acute GvHD. In summary, our study supports the entity of renal GvHD with histological features suggestive of cell-mediated renal injury. Albuminuria and urinary NAG levels may serve as early markers of renal impairment.

Predictive ability of urinary biomarkers for outcome in children with acute kidney injury.

Urinary neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-beta-D-glucosaminidase (NAG), and interleukin 18 (IL-18) were found to be useful for early detection of acute kidney injury (AKI). The objective of this study was to determine the predictive ability of biomarkers for mortality and variation in levels in relation to different stages of AKI, need for dialysis, etiologies, and with duration of hospital stay. Urinary NGAL, NAG, and IL-18 levels were measured in 50 children with AKI and 30 age- and gender-matched healthy controls. AKI was classified as per pediatric Risk, Injury, Failure, Loss, and End-stage (RIFLE) criteria. Median NGAL, NAG, and IL-18 values were significantly increased in AKI patients compared with controls (p < 0.001), with significant increase among risk, injury, and failure stages. Nonsurvivors had significantly higher median levels of NGAL (p = 0.008) and NAG (p = 0.018) than survivors. NGAL had highest area under the curve (AUC) at 0.750 [confidence interval (CI) 0.580-0.920], followed by NAG at 0.724 (CI 0.541-0.907), with sensitivity and specificity of 75% each; and IL-18 (AUC 0.688, CI 0.511-0.864), with sensitivity 62.5% and specificity 70.8%, for predicting mortality. Values were significantly higher in patients who required peritoneal dialysis (PD) than in those in whom it was not indicated. Levels were comparable among different etiologies. Only NGAL level was found to be a significant risk factor associated with longer duration of hospital stay. Urinary NGAL and NAG had modest predictive ability for mortality. Children requiring dialysis had significantly raised levels, and the NGAL level had significant association with duration of hospital stay.

Urinary enzymatic markers (N-acetyl-beta-D-glucosaminidase) in assessing the tubulointerstitial compartment in chronic glomerulonephritis related to odontogenic foci.

Chronic glomerulonephritis is related to focus infection. Odontogenic foci are frequently involved in glomerulonephritis. The relationship with the odontogenic focus infection can be demonstrated by the occurrence or aggravation of the symptoms of glomerulonephritis: proteinuria, haematuria, high blood pressure and oedema. Glomerular impairment in glomerulonephritis occurs together with inflammatory alterations of the tubulointerstitial compartment that can play an important part in the evolution of the disease. Tubular urinary markers can indicate the activation of this compartment during an infection of a focus, an odontogenic focus in our study.The paper aims at demonstrating the relationship between the odontogenic focus infection and tubulointerstitial lesions, assessed by a tubular urinary marker, N-acetyl beta-D glucosaminidase (NAG).We investigated the urinary N-acetyl beta-D glucosaminidase of 20 patients with chronic glomerulonephritis who presented odontogenic focus infections, comparing them with patients with chronic glomerulonephritis without odontogenic foci and of 20 controls, clinically healthy persons.Chronic glomerulonephritis patients with odontogenic focus infection presented clearly increased values as compared to clinically healthy control persons of urinary N-acetyl beta-D glucosaminidase.These patients underwent surgical intervention on the odontogenic focus under antibacterial prophylactic treatment. In 75% cases, the values of N-acetyl beta-D glucosaminidase diminished, indicating the favourable effect of the treatment of the odontogenic focus on the tubulointerstitial compartment in patients with chronic glomerulonephritis. In 25% cases this therapeutic treatment was associated with an increase of the values of urinary N-acetyl beta-D glucosaminidase, expressing its unfavourable effect on chronic glomerulonephritis.Urinary N-acetyl beta-D glucosaminidase indicated an etiopathogenetic relationship between the odontogenic focus and the tubulointerstitial compartment in chronic glomerulonephritis.

The Role of Urinary N-acetyl-beta-glucosaminidase in Diagnosis of Kidney Diseases

N-acetyl-beta-D-glucosaminidase (NAG) is a lysosomal enzyme present in the proximal convoluted tubules of the kidneys that may be used as a marker of proximal tubular damage and nephrotoxicity. An abnormal urinary NAG excretion has been reported in different kinds of renal disorders such as acute kidney injury, urinary tract infection, vesicoureteral reflux; diabetes mellitus; nephrotic syndrome; glomerulonephritis; hypertension; perinatal asphyxia; heavy metals poisoning; drug nephrotoxicity, renal allograft rejection; and heart failure. This paper provides an overview of the diagnostic value of urinary NAG in the nephrourology field.Keywords: N-acetyl-beta-D-glucosaminidase; Acute Kidney Injury; Kidney Diseases; Pyelonephritis; Hypertension; Vesico-Ureteral Reflux.

Effects of methyl cantharidimide tablets on urinary protein and enzymes in Beagle dogs

To investigate the nephrotoxic effects of methyl cantharidimide tablets on urinary protein and enzymes in Beagle dogs. Beagle dogs were randomly divided into negative control group(blank tablet), methyl cantharidimide tablets group (6.11,12.21, 24.42 mg x kg(-1)), continuously 30 days of oral adminiStration, once a day. The drug and control group were collected and determined fresh urine in 1, 2, 3 and 4 weeks of the administration; Serum urea nitrogen (BUN), creatinine (Crea), total protein (TP) and albumin (ALB) as well as sodium, potassium, chloride electrolyte were determined on 15 and 30 days of the administration; Urine albumin (mAlb), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin( NGAL), N-acetyl-beta-D-glucosaminidase (NAG), clusterin, beta2-microglobulin (beta2-MG), alpha1-microglobulin (alpha1-MG), alanine aminopeptidase( AAP) and im- munoglobulins IgG were tested on 15 and 30 days of the administration. Compared with the control group, urine protein and white blood cells was significantly increased in each dose group. On 15 days of the administration, mAlb were higher in each dose group, KIM-1, NGAL, clusterin, NAG and AAP were significantly higher in high-dose group, while the middle and low dose group had no significant difference, as well as blood SCr and BUN no obvious abnormalities. On 30 days, mAlb, KIM-1, clusterin, NAG, AAP were increased in each dose group, appearing dose-effect relationship, beta2-MG and NGAL levels were significantly increased in high-dose group. Contents above indicators were increased with significant dose and time relationship, and serum BUN, Scr were correlated, suggesting that urine mAlb, KIM-1, clusterin, NAG and AAP indicators that can sensitively respond the changes of proteins and enzymes in urine. Methyl cantharidimide tablets has a renal toxicity, urine mAlb, KIM-1, clusterin, NAG and AAP can be used as the early nephrotoxic biomarkers of methyl cantharidimide tablets.

Evaluation of urinary N-acetyl-beta-D-glucosaminidase as a marker of early renal damage in patients with type 2 diabetes mellitus

To evaluate the clinical usefulness of urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion for the detection of early tubular damage in type 2 diabetes mellitus (T2DM). Thirty six patients with T2DM were divided into two groups based on urinary albumin to creatinine ratio (ACR): normoalbuminuria (ACR <30 mg/g; n=19) and microalbuminuria (ACR =30-300 mg/g; n=17). The following parameters were determined in both groups: urinary NAG and albumin, serum and urine creatinine, fasting plasma glucose and glycated hemoglobin (HbA1c). Urinary NAG levels [Units/g creatinine; median (range)] were significantly increased in microalbuminuria group [17.0 (5.9 - 23.3)] compared to normoalbuminuria group [4.4 (1.5 - 9.2)] (P<0.001). No differences between groups were observed in fasting glucose, HbA1c, serum creatinine levels and estimated glomerular filtration rates (eGFR). Urinary NAG positively correlated with ACR (r=0.628; p<0.0001), while no significant association was observed between NAG and glycemia, HbA1c, serum creatinine and eGFR. The increase of urinary NAG at the microalbuminuria stage of diabetic nephropathy (DN) suggests that tubular dysfunction is already present in this period. The significant positive association between urinary NAG excretion and ACR indicates the possible clinical application of urinary NAG as a complementary marker for early detection of DN in T2DM.

Early markers of obesity-related renal injury in childhood.

Childhood obesity has become a global epidemic. Recent epidemiological data suggest that obesity is associated with increased risk of renal injury in children. The onset of obesity-associated renal disease is insidious and asymptomatic, so early markers will be extremely useful in its prevention and treatment. Biomarker discovery can be focused on unbiased or biased (candidate) approaches. Unbiased approaches using innovative technologies, such as proteomics and metabolomics, have uncovered candidates that are emerging as plausible biomarkers for such renal disorders as obstructive uropathy and diabetic nephropathy. Biased approaches are based on hypotheses related to glomerular or tubular injury pathophysiology in obesity. Goknar et al. (Pediatric Nephrology 2014; doi: 10.1007/s00467-014-2829-0 ) recently evaluated early urine renal injury markers, namely, microalbuminuria, N-acetyl-beta-D-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin, and kidney injury molecule (KIM)-1, in obese children. They reported that obese children had higher urinary NAG and KIM-1 levels than healthy controls. Longitudinal observation studies are needed to evaluate whether these tubular damage markers are useful as early markers of renal injury in obese children.

Ureic clearance granule, alleviates renal dysfunction and tubulointerstitial fibrosis by promoting extracellular matrix degradation in renal failure rats, compared with enalapril

Ethnopharmacological relevanceChinese herbal compound prescription has a unique therapeutic action on chronic kidney disease (CKD) in China. In clinics, Uremic Clearance Granules (UCG), a compounded Chinese patent medicine, has been frequently used to treat chronic renal failure (CRF) patients for nearly 30 years, however, the deep therapeutic mechanisms involved in vivo remain a challenge. This study aims to demonstrate the effects and mechanisms of UCG on renal dysfunction and tubulointerstitial fibrosis by regulating extracellular matrix (ECM) degradation and transforming growth factor (TGF)-beta1/Smad signaling activity in vivo, compared with enalapril. Materials and methodsTwenty-six rats were randomly divided into 4 groups, a sham-operated group (Sham group), a vehicle-intervened group (Vehicle group), a UCG-treated group (UCG group) (5g/kg/day) and an enalapril-treated group (Enalapril group) (20mg/kg/day). The rats with renal failure were induced by adenine (150mg/kg/day) and unilateral ureteral obstruction (UUO), and killed on day 35 after the administration. Proteinuria, urinary N-acetyl-beta-D-glucosaminidase (UNAG), blood biochemical parameters, renal morphological changes, collagen type IV (CIV), matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitors of metalloproteinase (TIMP)-1, as well as the key molecular protein expressions in TGF-beta1/Smad signaling pathway were observed, respectively. ResultsAdenine administration and UUO induced severe renal damages, as indicated by renal dysfunction, proteinuria and the marked histopathological injuries in the tubules and interstitium, which were associated with MMP-2/TIMP-1 imbalance and TGF-beta1/Smad signaling activity, as shown by up-regulation of the protein expressions of TGF-beta1, TGF-beta receptor type I (RI), TGF-beta receptor type II (RII), Smad2/3, phosphorylated-Smad2/3 (p-Smad2/3) and Smad4, as well as down-regulation of the protein expression of Smad7 in the kidney. UCG treatment, however, significantly not only attenuated renal dysfunction and tubulointerstitial fibrosis, but also improved the protein expressions of MMP-2, TIMP-1, TGF-beta1, TGF-beta RI, p-Smad2/3, Smad4 and Smad7 in the kidney. Besides, the effects of UCG were stronger than those of enalapril partly. ConclusionUCG similar to enalapril, is renoprotective via ameliorating renal dysfunction and tubulointerstitial fibrosis in the renal failure model. The potential mechanisms by which UCG exerts its therapeutical effects in vivo are through promoting ECM degradation and regulating MMP-2/TIMP-1 balance or signaling molecular activity in TGF-beta1/Smad pathway in the kidney. These findings suggest that UCG treatment is undoubtedly useful in preventing the progression of CRF.