Performance of urinary kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, and N-acetyl-beta-D-glucosaminidase to predict chronic kidney disease progression and adverse outcomes

Urinary biomarkers can predict the progression of chronic kidney disease (CKD). In this study, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and N-acetyl-β-D-glucosaminidase (NAG) were correlated with the stages of CKD, and the association of these biomarkers with CKD progression and adverse outcomes was determined. A total of 250 patients, including 111 on hemodialysis, were studied. Urinary KIM-1, NGAL, and NAG were measured at baseline. Patients not on dialysis at baseline who progressed to a worse CKD stage were compared with those who did not progress. The association of each biomarker and selected covariates with progression to more advanced stages of CKD, end-stage kidney disease, or death was evaluated by Poisson regression. NGAL was moderately correlated (rs=0.467, P<0.001) with the five stages of CKD; KIM-1 and NAG were also correlated, but weakly. Sixty-four patients (46%) progressed to a more advanced stage of CKD. Compared to non-progressors, those patients exhibited a trend to higher levels of KIM-1 (P=0.064) and NGAL (P=0.065). In patients not on dialysis at baseline, NGAL was independently associated with progression of CKD, ESKD, or death (RR=1.022 for 300 ng/mL intervals; CI=1.007-1.037, P=0.004). In patients on dialysis, for each 300-ng/mL increase in urinary NGAL, there was a 1.3% increase in the risk of death (P=0.039). In conclusion, urinary NGAL was associated with adverse renal outcomes and increased risk of death in this cohort. If baseline urinary KIM-1 and NGAL predict progression to worse stages of CKD is something yet to be explored.

Plomo y nefropatía: biomarcadores urinarios en la detección de daño renal precoz / Blood lead levels and markers of renal dysfunction among mechanical workshop workers

The role of lead (Pb) as an environmental cause of nephropathy is difficult to ascertain due to the difficulty to determine clinically its exposure. Aim: To assess lead levels and renal function in a group of males working in mechanical workshops. Material and Methods: Blood and urine samples were obtained from 100 mechanical workshop workers aged 38 ± 16 years and 95 non-exposed office clerks aged 37 ± 17 years. Blood lead and creatinine levels were determined. In exposed workers, urinary excretion of intestinal alkaline phosphatases (IAP) and N-acetyl-glucosaminidase (NAG) were measured as early markers of renal failure. Results: Blood lead levels were 66.4 ± 43 and 33.6 ± 18 µg/L among mechanical workshop workers and non-exposed controls, respectively, p < 0.01. The figures for serum creatinine were 0.9 ± 0.1 and 0.9 ± 0.1 respectively, p = NS. Among exposed workers urinary excretion of IAP was 0.47 ± 0.6 U/L and of NAG, 0.92 ± 1.1 U/L. There was a positive correlation between blood lead levels and NAG excretion (r = 0.284) and IAP excretion (r = 0.346). Conclusions: Exposed workers had higher blood lead levels and there was a weak positive association between these levels and the urinary excretion of NAG and IAP.

Environmental Exposure to Arsenic, Lead, and Cadmium in People Living near Janghang Copper Smelter in Korea

Concentrations of heavy metals exceed safety thresholds in the soil near Janghang Copper Refinery, a smelter in Korea that operated from 1936 to 1989. This study was conducted to evaluate the level of exposure to toxic metals and the potential effect on health in people living near the smelter. The study included 572 adults living within 4 km of the smelter and compared them with 413 controls group of people living similar lifestyles in a rural area approximately 15 km from the smelter. Urinary arsenic (As) level did not decrease according to the distance from the smelter, regardless of gender and working history in smelters and mines. However, in subjects who had no occupational exposure to toxic metals, blood lead (Pb) and cadmium (Cd) and urinary Cd decreased according to the distance from the smelter, both in men and women. Additionally, the distance from the smelter was a determinant factor for a decrease of As, Pb, and Cd in multiple regression models, respectively. On the other hands, urinary Cd was a risk factor for renal tubular dysfunction in populations living near the smelter. These results suggest that Janghang copper smelter was a main contamination source of As, Pb, and Cd, and populations living near the smelter suffered some adverse health effects as a consequence. The local population should be advised to make efforts to reduce exposure to environmental contaminants, in order to minimize potential health effects, and to pay close attention to any health problems possibly related to toxic metal exposure.

Urine alpha1-microglobulin is a better marker for early tubular dysfunction than beta2-microglobulin among tenofovir-exposed human immunodeficiency virus-infected men who have sex with men

Objectives: Men who have sex with men are at risk of tenofovir nephrotoxicity due to its wide use in both treatment and prophylaxis for human immunodeficiency virus infection, but little is known about the urinary biomarkers of early renal dysfunction in this population. This study aims to identify useful biomarkers of early renal dysfunction among human immunodeficiency virus-infected men who have sex with men exposed to tenofovir.Methods: In a cross-sectional study urinary alpha1-microglobulin, beta2-microglobulin, N-acetyl-B-n-glucosaminidase and albumin were measured and expressed as the ratio-to-creatinine in 239 human immunodeficiency virus-infected men who have sex with men who were treatment naïve or receiving antiretroviral therapy with tenofovir-containing or non-tenofovir-containing regimens. Additionally, 56 patients in the non-antiretroviral therapy group started a tenofovir-containing regimen and were assessed after 3 and 6 months on antiretroviral therapy.Results: Both the frequency of alpha1-microglobulin proteinuria (alpha1-microglobulin-creatinine ratio >25.8 mg/g) and the median urinary alpha1-microglobulin-creatinine ratio were higher in the tenofovir disoproxil fumarate group than the other two groups (all p< 0.05). A higher frequency of beta2-microglobulin proteinuria (beta2-microglobulin-creatinine ratio >0.68 mg/g) was also observed in the tenofovir group (28.9%) compared to the non-tenofovir group (13.6%, p= 0.024). There were no significant differences between groups for N-acetyl-β-n-glucosaminidase and albumin. In the longitudinal study, the median urinary alphat-microglobulin-creatinine ratio after 3 and 6 months on tenofovir-containing therapy (16.8 and 17.3 mg/g) was higher than baseline (12.3 mg/g, p= 0.023 and 0.011, respectively), while no statistically important changes were observed in urinary beta2-microglobulin-creatinine ratio or in the other biomarkers after 3 and 6 months on antiretroviral therapy (all p> 0.05).Conclusion: Urinary alphat-microglobulin seems to be a more sensitive and stable indicator of tubular dysfunction than urinary beta2-microglobulin for assessing tenofovir-related nephrotoxicity and can be significantly altered after tenofovir exposure.

Urinary markers for early detection of Diabetic Nephropathy in type 1 Diabetes Mellitus

Background: diabetic nephropathy [DN] is a serious complication of diabetic mellitus associated with increased risk of morbidity and mortality. Diagnostic markers to detect DN at early stage are important as early intervention can slow loss of kidney functions and improve patient outcomes. N-acetyl Beta d-glucosaminidase [NAG] is a lysosomal enzyme, present in high concentrations in renal proximal tubular cells, Gamma-glutamyltransferase [GGT] is an enzyme which located along the proximal tubular brush border, Malondialdehyde [MDA] is a highly toxic product, formed in part by lipid oxidation derived free radicals, Reactive carbonyl derivatives [RCD[S]] is an oxidative stress marker in urine, as a measure of the oxidative modification of proteins and beta-2-microglobulin is filtered by the glomerulus, absorbed and catabolized by the proximal tubules. The aim of this study is to investigate the urinary outcome of these markers as early detectors of diabetic nephropathy in type 1 diabetic children

Subjects and methods: This case-control study included 67 children with type 1 diabetes mellitus [33 male; 34 female], age [11.03 +/- 1.05 years] and thirty one age [10.58 +/- 1.11 years] and sex [13 male; 18 female] matched healthy children [13 male; 18 female]. Type 1 diabetic children were further subdivided into microalbuminuric and normoalbuminuric subgroups according to microalbuminuria concentration [30 mg/ g creatinine]. Age, sex, diabetic duration and the current daily insulin dose, and family history of diabetes, weight, height, body mass index, systolic and diastolic blood pressure were recorded. Fasting plasma glucose, glycated hemoglobin, blood urea nitrogen, plasma creatinine, urinary creatinine, micoalbumin, N-acetyl-B-D glucosaminidase [NAG], Gama glutamyl transferase [GGT], Beta-2-microglobulin, Malondialdehyde [MDA] and Reactive carbonyl groups [RCDS[S]] were measured in all subjects

Results: a significant increase in tubular injury markers of diabetes [NAG, GGT, beta-2-microglobulin] and oxidative stress parameters [MDA, RCDS[S]] as compared to control subjects was found. Microalbuminuric subjects showed a significant elevatation in the urinary markers including NAG, GGT, beta-2-microglobulin, MDA, RCDS[S] as compared to normoalbuminuric subjects. The studied urinary tubular enzymes [NAG, GGT], oxidative stress markers [MDA, RCDS[S]] and Beta-2- microglobulin showed positive correlations with one another

Conclusion: The results of this study introduced the possibility of depending on tubular enzymes [NAG, GGT], oxidative stress markers [MDA, RCDS[S]] and Beta2 microglobulin as early, reliable, and sensitive predictors for diabetic nephropathy. The NAG activity index proved to be the most sensitive biomarker, then beta-2- microglobulin for early discovering the tubule cells damage

Evaluation of urinary N-acetyl-beta-D-glucosaminidase as a marker of early renal damage in patients with type 2 diabetes mellitus / Avaliação da N-acetil-beta-D-glucosaminidase urinária como marcador de dano renal precoce em pacientes com diabetes melito tipo 2

Objective 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). Subjects and methods 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). Results 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. Conclusions 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. .

Objetivo Avaliar a utilidade clínica da excreção urinária da N-acetil-beta-D-glucosaminidase (NAG) para a detecção de dano tubular precoce no diabetes melito tipo 2 (DM2). Sujeitos e métodos Foram estudados trinta e seis pacientes com DM2 que se dividiram em dois grupos com base na excreção urinária de albumina (EUA): normoalbuminúrico (EUA <30 mg/g de creatinina; n=19) e microalbuminúrico (EUA =30‐300 mg/g de creatinina; n=17). Em ambos os grupos foram determinados os seguintes parâmetros: NAG e albumina urinária, creatinina sérica e urinária, glicemia de jejum e hemoglobina glicada (HbA1c). Resultados Os níveis de NAG urinária [unidades/g de creatinina; mediana (intervalo interquartílico)] foram significativamente maiores no grupo microalbuminúrico [17,0 (5,9 - 23,3)] em comparação com o grupo normoalbuminúrico [4,4 (1,5 - 9,2)] (p<0,001). Não se observaram diferenças significativas entre os dois grupos nos níveis de glicemia de jejum, HbA1c, creatinina sérica e taxa de filtração glomerular estimada (TFGe). A NAG urinária se correlacionou positivamente com o EUA (r=0,628, p<0,0001), não sendo observada associação significativa da NAG com glicemia, HbA1c, creatinina sérica e TFGe. Conclusões O aumento da NAG urinária na fase de microalbuminúria da nefropatia diabética (ND) sugere que a disfunção tubular já está presente nesse período. A associação positiva significativa entre a excreção urinária da NAG e EUA indica a possível aplicação clínica da NAG urinária como marcador complementar para a detecção precoce da ND no DM2. .

Role of Urinary Levels of Endothelin-1, Monocyte Chemotactic Peptide-1, and N-Acetyl Glucosaminidase in Predicting the Severity of Obstruction in Hydronephrotic Neonates

PURPOSE: Antenatal hydronephrosis (AH) is found in 0.5%-1% of neonates. The aim of the study was to assess the urinary concentrations of 3 biomarkers, endothelin-1 (ET-1), monocyte chemotactic peptide-1 (MCP-1), and N-acetyl-glucosaminidase (NAG) in severely hydronephrotic neonates. MATERIALS AND METHODS: Neonates with a history of prenatal hydronephrosis were enrolled in the prospective study in 2 groups. Group 1 included neonates with severe forms of obstruction requiring surgical intervention and group 2 included neonates with milder forms of obstruction without any functional impairment. Fresh voided urinary levels of ET-1, MCP-1, and NAG were measured and their ratios to urinary Cr were calculated. RESULTS: Fourty-two neonates were enrolled into the 2 groups: group 1, 24 patients (21 male, 3 female); group 2, 18 neonates (16 male, 2 female). There were no statistically significant differences between urinary ET-1, NAG, MCP-1 values, and ET-1/Cr and NAG/Cr ratios in groups 1 and 2. The urinary MCP-1/Cr ratio was significantly higher in group 1 than in group 2. For comparison of groups 1 and 2, the cut-off values were measured as 0.5709 ng/mg (sensitivity, 75%; specificity, 67%; positive predictive value [PPV], 71%; negative predictive value [NPV], 71%), 0.927 ng/mg (sensitivity, 77%; specificity, 72%; PPV, 77%; NPV, 72%), and 1.1913 IU/mg (sensitivity, 62%; specificity, 67%; PPV, 68%; NPV, 60%) for ET-1/Cr, MCP-1/Cr, and NAG/Cr ratios, respectively. CONCLUSIONS: The urinary MCP-1/Cr ratio is significantly elevated in neonates with severe obstruction requiring surgical intervention. Based upon these results, urinary MCP-1/Cr may be useful in identification of severe obstructive hydronephrosis in neonates.

N-acetil-β-D-glicosaminidase como biomarcador precoce de disfunção renal para a exposição ocupacional ao chumbo inorgânico / N-acetyl-β-D-glucosaminidase as an early biomarker of renal dysfunction due to occupational exposure to inorganic lead

OBJETIVO: Este estudo teve como objetivo averiguar a atividade enzimática da N-acetil-β-D-glicosaminidase (NAG) como possível biomarcador precoce de disfunção renal para a exposição ocupacional ao chumbo inorgânico. MATERIAIS E MÉTODOS: Foi selecionado um grupo de 30 pessoas do sexo masculino expostas ao chumbo inorgânico em uma fábrica de baterias localizada no estado do Paraná. Fizeram parte do grupo os funcionários que mostraram valores de chumbo sanguíneo inferiores a 40 mg/dl. O grupo controle foi representado por 15 adultos saudáveis com similaridade em relação à idade e ao gênero do grupo exposto. Foram determinados os níveis de plumbemia, do ácido d-aminolevulínico urinário e a atividade da NAG urinária. RESULTADOS E DISCUSSÃO: Foi evidenciado que a atividade urinária da NAG foi significativamente maior (p < 0,05; teste U de Mann-Whitney) no grupo exposto ao chumbo inorgânico quando comparado ao grupo controle, e houve uma correlação negativa com significância (p < 0,05; correlação de Spearman Rank Order) entre o indicador biológico de exposição plúmbica e a atividade urinária da NAG. CONCLUSÃO: Os resultados demonstraram que o aumento da atividade urinária da NAG pode ser utilizado como um biomarcador precoce da exposição ao chumbo inorgânico.

OBJECTIVE: This study aimed to verify the enzymatic activity of N-acetyl-β-D-glucosaminidase (NAG) as a possible early biomarker of renal dysfunction due to occupational exposure to inorganic lead. MATERIALS AND METHODS: We selected a group of 30 males that had been exposed to inorganic lead in a battery factory in the state of Paraná. This group comprised those employees whose blood lead levels were below 40 mg/dl. The control group consisted of 15 healthy adults of similar age and gender compared with the exposed group. Blood lead concentrations, d-aminolevulinic acid levels and urinary NAG activity were measured. RESULTS AND DISCUSSION: It was shown that urinary NAG activity was significantly higher (p < 0.05, U test of Mann-Whitney) in the exposed group in comparison to the control group, and there was a significant negative correlation (p < 0.05, Spearman Rank Order correlation) between the biological indicator of lead exposure and urinary NAG activity. CONCLUSION: The results showed that the increase of urinary NAG activity may be used as an early biomarker of the exposure to inorganic lead.

Urinary N-acetyl-beta-D-glucosaminidase as a diagnostic marker of acute pyelonephritis in children

Prompt diagnosis and localization of pyelonephritis are of great importance in children. The urinary excretion of enzymes, and in particular N-acetyl-beta-D-glucosaminidase [NAG], is considered a simple noninvasive marker for detection of renal tubular dysfunction due to pyelonephritis. This study was performed to determine the diagnostic value of urinary NAG in acute pyelonephritis. In a quasi-experimental study conducted on 72 children with confirmed pyelonephritis, we measured urinary NAG, creatinine, and NAG-creatinine ratio before and after the treatment. Diagnostic values of these parameters were evaluated by considering the patients before and after the treatment as disease-positive and disease-negative groups, respectively. The patients were 18 boys [25.0%] and 54 girls [75.0%] with a mean age of 43.0 +/- 39.0 months. The mean levels of urinary NAG were 12.20 +/- 6.14 U/L and 5.46 +/- 7.98 U/L before and after the treatment, respectively [P < .001]. The sensitivity and specificity of urinary NAG-creatinine ratio for diagnosis of pyelonephritis were 73.6% and 77.3%, respectively, with a cutoff point of 10.16 U/g [area under the curve = 0.76, 95% confidence interval, 0.67 to 0.76]. Significantly higher levels of urinary NAG were found in those who had a negative urine culture at diagnosis [8.8 +/- 10.4 U/L] compared to those with a positive urine culture [4.5 +/- 8.7 U/L]. We concluded that urinary NAG is elevated in children with pyelonephritis and it can be considered as a further criterion in the diagnosis of upper urinary tract infection

Increased urinary n-acetyl-beta-d-glucosaminidase activity in children with hydronephrosis

OBJECTIVE: Hydronephrosis leads to deterioration of renal function. As urinary N-acetyl-beta-D-glucosaminidase (U-NAG) activity is considered a sensitive marker of renal tubular impairment, our aim was to measure U-NAG in children with hydronephrosis and to look for a relationship among selected clinical parameters. MATERIALS AND METHODS: We studied 31 children (22 boys and 9 girls, mean age 2.3 ± 2.5 years) with hydronephrosis grade 1-4 that had U-NAG/creatinine ratio (U-NAG/Cr) measured. RESULTS: The U-NAG/Cr was significantly higher in patients with hydronephrosis compared to reference data (p = 0.002). There was no difference in U-NAG/Cr between children with unilateral and bilateral hydronephrosis (p = 0.51). There was no significant difference in U-NAG/Cr between children with grades 1-3 (pooled data) and grade 4, respectively (p = 0.89). There was no correlation between U-NAG/Cr and the grade of hydronephrosis (r = 0.01). CONCLUSIONS: U-NAG/Cr is increased in children with hydronephrosis grade 1-4, and there is no relationship with the grade of hydronephrosis. U-NAG is a useful marker of renal tubular dysfunction, however its relationship with the degree of kidney damage in patients with hydronephrosis should be considered as doubtful.

[Diagnostic value of urinary N-Acetyl Glucose Aminidase in pyelonephritic patients]

Urinary tract infection [UTI] is one of the most common bacterial infections among children and its prevalence is between 5-7% in females and 1-1.6% in males.Urosepsis, febrile seizure, renal insufficiency and hypertension are common complications of acute pyelonephritis in children. The aim of this study was to evaluate the diagnostic value of urinary NAG in pyelonephritic patients. This is a Quasi Experimental study conducted between April 2005 and May 2006 on 72 children admitted in Mofid Hospital due to pyelonephritis. The first sample [fresh random urine] was obtained and its levels NAG and Creatinin were measured. The second one was obtained on 48th hour of after-treatment period. We examined pyelonephritic children [75% female] with mean age of 43 +/- 39 months. Post-treatment urinary NAG lavel was significantly higher than pre-treatment. Urinary NAG revealed to have a sensitivity of 78% and specificity of 72% in diagnosis of pyelonephritis. There was no significant correlation between urinary NAG level and CBC, ESR, CRP, Urinary WBC, Ultrasonography, DMSA scan and VCUG. We concluded that Urinary NAG is a sensitive and specific test in diagnosis of pyelonephritis

Effect of shock wave reapplication on urinary n-acetyl-beta-glucosaminidase in canine kidney

OBJECTIVE: Renal tubular damage can be assessed with the aid of urinary dosing of N-acetyl-beta-glucosaminidase (NAG) and it is possible to demonstrate a significant correlation between shock wave and damage to renal parenchyma. The objective of this study was to assess the effect of shock wave reapplication over urinary NAG in canine kidney. MATERIALS AND METHODS: The authors submitted 10 crossbred dogs to 2 applications of 2000 shock waves in a 24-hour interval in order to assess urinary NAG values after 12, 24, 36 and 48 hours. RESULTS: Twelve hours following the first shockwave application there was an increase in NAG of 6.47 ± 5.44 u/g creatinine (p < 0.05). Twelve hours and 24 h following the second application there was no increase in the urinary enzyme, - 2.56 ± - 7.36 u/g creatinine and 2.89 ± - 7.27 u/g creatinine, respectively (p > 0.05). CONCLUSION: Shock wave reapplication with a 24-hour interval did not cause any increase in urinary NAG.

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

We measured urinary albumin excretion rate (AER) and N-acetyl-beta-D-glucosaminidase (NAG) activity in relation to disease duration, acetylated hemoglobin (HbA1c), hypertension and puberty in 44 children and adolescents with type 1 diabetes mellitus. AER and Urinary NAG activity were significantly higher in the patients compared to controls (AER 19.4 +/-; 35.8 vs 4.7 +/- 4.4, NAG activity 5.6 +/- 0.6U vs. 1.6 +/- 0.2U). Microalbuminuria was present in seven patients (15.9%), all of whom were pubertal. There was no correlation between AER and urinary NAG activity. There was a significant direct correlation between AER and disease duration (P <0.05), HbA1c (P < 0.05), diastolic blood pressure (P <0.05) and puberty (P <0.05). None of the microalbuminuria related variables was significantly correlated with urinary NAG activity. Puberty was an independent factor for elevated urinary NAG activity. This study shows that urinary NAG is elevated in children and adolescents with type 1 diabetes mellitus, but is not associated with AER related factors except for puberty. Urinary NAG activity does not appear to be a useful marker for early detection of diabetic nephropathy in children and adolescents with type 1 diabetes mellitus.

Study of some renal function tests in epileptic children on antiepileptic drug monotherapy

In the present study we tried to verify the renal function status in epileptic children at diagnosis and 4 months following AED monotherapy. This study was carried out on 45 children, 27 males and 18 females aged 5-16 years, suffering from different types of freshly diagnosed epilepsy. They were classified into 3 groups: Group 1: Consisted of 15 patients treated by carbamazepine [CBZ] [Tegretol] monotherapy. Group II: Consisted of 15 patients treated by sodium valproate [VPA] [Depakine] monotherapy. Group Ill: Consisted of 15 patients treated by phenytoin [PHE] [Epanutin] monotherapy. In addition 20 healthy children of matched age and sex, products of nonepileptic families, with normal hepatic and renal function tests, served as a control group. All children included in this study were subjected to the following: determination of fasting blood urea, estimation of fasting serum creatinine, estimation of creatinine clearance, determination of urinary albumin/24 hours, urinary N-acetyl-8-D-glucosaminidase [NAG]/24h and urinary alpha-1 microglobulin [alpha-1MG]/24h. Our results revealed the following: Normal renal glomerular and tubular function tests in patients before therapy. Normal renal glomerular function tests [blood urea nitrogen serum creatinine, creatinine clearance, routine urine analysis and 24 hr urinary albumin] in all patients after AED therapy. Significant increase in urinary NAG was observed in all patient groups after therapy and this increase was highest in patients receiving valproate monotherapy. Significant increases in urinary alpha-1MG in patients receiving carbamazepine or phenytoin with no change following VPA therapy were recorded

Renal tubular dysfunction in patients with type 2 diabetes mellitus

It is well established that the detection of microalbuminuria in patients with diabetes mellitus indicates the presence of glomerular involvement in early renal damage. Recent studies have demonstrated that there iso also a tubular component of renal complications in diabetes, as shown by the detection of renal tubular proteins and enzymes in urine. So, the objective of this study was to determine the activity of urinary enzymes [N-aceiyl-beta-D-glucosaminidase [NAG], a lysosomal enzyme, gamma-glutamyltranspeptidase [GGT], alkaline phosphalase [ALP], brush border enzymes and /32 microglobulin [beta 2MG,] as one of the tubular proteins] as markers of tubular damage which may reflect early stage of diabetic nephropathy [DN] and to clarify the importance of estimation of these enzymes as noninvasive cheap tools in monitoring the course of DN [degree of proteinuria]. Also we studied the serum level of angiolensine converting enzyme [ACE] to evaluate the endothelial disorder in diabetic patients. Patients and Methods: 3 groups of non smoker type 2 diabetic patients were studied, 1[st] group was 20 normo-albuminuric diabetic patients, 2[nd] group was 20 patients with microalbuminurea [urinary albumin is >30 mg - <300 mg/day], and the 3[rd] group was 20 patie!ts with macroalbuminuria [: 300 mg/day]. Another 15 healthy age and sex matched subjects were recruited as a control group. For each patient and control subject the followings were estimated: [1] urinary glucose, 2 hours postprandial blood glucose, and glycated haemoglohin as parameters of gl, vcaemic control [2] blood urea, serum creatinine, 24-hour urinary protein and microalbuminuria to detect DN, ['3,] Serum ACE, urinary NAG. ALP, GGT and beta 2 microglobulin. The serum urinary NAG, ALP, beta 2MG, HbA[1c] and 2-hour postprandial blood glucose were significantly higher in the diabetic groups compared to controls. While GGT was significantly lower in the diabetic groups compared to controls. Also the increase in serum ACE, urinary NAG, ALP and beta 2MG positively correlated with the degree of albuminuria, HbA[1c] and 2-hour postprandial blood glucose while urinary GGT negatively correlated with the previous parameters. The significant progressive increase in ACE activity in the studied groups supports the hypothesis of ACE activity being an essential partner in the development of DN The elevation of the levels of NAG, ALP and beta 2 microglobulin, and the decrease in the level of GGT in the first group and the progressive change in their levels with the pathological increase in the level of urinary albumin, suggest that these changes are useful in the diagnosis of early stage of DN before the development of microalbuminuria. GGT and NAG appear more simple and readily available compared with others

Evaluación del daño renal post-litotripsia extracorpórea: experiencia Hospital Clínico de la Universidad de Chile / Evaluation of renal damage secondary to extracorporeal shock ware lithotripsy: experience at the Hospital Clínico de la Universidad of Chile

Es controversial determinar la magnitud del posible daño del parénquima renal secundario a las ondas de choque utilizadas en litotripsia extracorpórea (LEC). La elevación urinaria de la actividad de la enzimaN-acetil-ß-D-glucosaminidasa (NAG) puede reflejar este daño y su evolución en el tiempo. El objetivo de este estudio será precisar la magnitud y duración del daño renal posterior a LEC, a través de mediciones de NAG y su correlación con algunos parámetros clínicos. Se realizó un estudio prospectivo en 15 pacientes, de ambos sexos, portadores de litiasis renal única, sin otra patología renal asociada. Se determinó la actividad urinaria de NAG antes y 1, 7 y 30 días post LEC. Se midió la relación entre NAG (U/L) y creatinina (mmol/L) urinarias, expresada como índice NAG (U/mmol). Se consideró su relación con: a) tamaño, b) ubicación y c) número de impactos utilizados. Paralelamente, se determinó NAG urinario como referencia en 5 pacientes sanos y en un portador de daño tubular renal. En 7 de 15 pacientes, se verificó un incremento en el índice NAG al día siguiente de la LEC, regresando a valores basales, en la mitad de los casos, al cabo de una semana. Esta elevación fue menor comparada con la observada en el paciente con daño renal. No se encontró diferencias entre el número de impactos y ubicación de la litiasis, con el valor del índice NAG. Cinco de siete pacientes que presentaron alza enzimática tenían litiasis mayor a 1 cm. Se puede señalar que la LEC produce cierto grado de daño renal, aunque de baja magnitud, variable, reversible a corto plazo y asociado al tamaño de los cálculos, similar a lo descrito en la literatura. Si bien la muestra empleada es pequeña para determinar diferencias estadísticamente significativas, nuestra investigación aparece como un informe preliminar para objetivar el potencial daño renal post-LEC y permitirá evaluar la implementación de esta técnica de medición en el futuro.

Early detection of renal disease in occupational hydrocarbon exposure by using non Invasive biomarkers

Early detection of renal dysfunction resulting from exposure to a nephrotoxin is important since this is the first step in the progressive loss of renal functions and ultimately progression to renal failure which are characteristic of the nephrotoxic cascade. Using modem technology, minute quantities of LMWP and urinary enzymes can be measured. Excretory patterns that are characteristic for site and mechanism of renal injury often can be found. This study was carried out to investigate the link between the occupational hydrocarbon exposure and nephrotoxicity by using the non invasive urinary markers for early detection of subclinical reversible conditions. Twenty adult men works as paint sprayer [chronic exposure] composing the first group and compared them to twenty adult males with a minimal exposure matched age, weight, height, blood pressure and residential ares, composing the second group as a control group. The results showed a significant increase in B2-microglobulin [B2 mic] p<0.003, Retinol binding protein [RBP] p<0.001, N-acetyl-B-D-glucosaminidas [NAG] p<0.0001 in the first group as compared to the normal control group. Serum creatinine shows no difference between the two groups, As a conclusion, by using non invasive methods our results are in keeping with the hypothesis that hydrocarbon exposure through paint spraying may result in active proximal tubular damage which may be reduced by improvement of protection at their work site as heavy duty overalls, thick gloves and more important air-fed mask for the airway and face protection. Follow up studies are necessary to assess the prognostic value of early changes detected in workers chronically exposed to organic solvents

Clinical value of urinary alpha 1-microglobulin and N-acetyl beta-D-glucosaminidase in pediatric renal diseases

Measuring urinary alpha[1]-microglobulin [alpha1 MG] and acetyl beta-D-glucosa-minidase [NAG] excretion is widely used as a valuable clinical tool in assessing renal glomerular and tubular lesion in adult, However few data are on values for urinary alpha[1]MG and NAG in pediatrics. The aim of this study was to measure urinary alpha[1]MG and NAG in children in health and diseases and if these might reflect disease activity. We studied 31 children with some clinical renal diseases during active disease and remission over follow-up period of 3 years and 10 healthy children were included as a control group. 10 children with nephritic syndrome [group I], 11 children with nephrotic syndrome [group II] and 10 children with lupus nephritis [group III]. Urinary alpha[1]MG and NAG was measured by radial immunodiffusion technique assay and colorimetric assay respectively. Our results showed significantly higher levels of urinary alpha[1]MG in children with active disease versus controls. The urinary alpha[1]IMG level was in the control [19.67 +/- 8.481, in group 1[53.61 +/- 2.95, p<0.05]. In group 11[91.29 +/- 31.91 p<0.01] in group III [81.27 +/- 15.09, p<0.001] compared to control. Urinary alpha[1] MG level showed no significant difference in patients in remission period versus control [p>0.05]. Urinary level of alpha[1] MG showed significant correlation to proteinuria in group I [r=0.783<0.01] and group 11 [r=0.925, p<0.001] only. On the other hand urinary NAG level showed significantly higher levels in all patients groups [group I, group II, group III], compared to controls [p<0.001] and there was no significant difference in all patients in remission phase compared to controls [p >0, 5]. There was a significant positive correlation between urinary alpha[1]MG and NAG

Urinary N-acetyl--D-glucosaminidase and Malondialdehyde as a Markers of Renal Damage in Burned Patients

This study was aimed to evaluate renal dysfunction during three weeks after the burn injuries in 12 patients admitted to the Hallym University Hankang Medical Center with flame burn injuries (total body surface area, 20-40%). Parameters assessed included 24-hr urine volume, blood urea nitrogen, serum creatinine, creatinine clearance, total urinary protein, urinary microalbumin, 24-hr urinary N-acetyl--D-glucosaminidase (NAG) activity, and urinary malondialdehyde (MDA). Statistical analysis was performed using repeated measures ANOVA test. The 24-hr urine volume, creatinine clearance, and urinary protein significantly increased on day 3 post-burn and fell thereafter. The urine microalbumin excretion showed two peak levels on day 0 post-burn and day 3. The 24-hr urinary NAG activity significantly increased to its maximal level on day 7 post-burn and gradually fell thereafter. The urinary MDA progressively increased during 3 weeks after the burn injury. Despite recovery of general renal function through an intensive care of burn injury, renal tubular damage and lipid peroxidation of the renal tissue suggested to persist during three weeks after the burn. Therefore, a close monitoring and intensive management of renal dysfunction is necessary to prevent burn-induced acute renal failure as well as to lower mortality in patients with major burns.