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

Comparison of the effects of repeated dose treatments of lornoxicam and meloxicam on renal functions in rats

We aimed to investigate the renal effects of meloxicam, a preferential cyclooxygenase-2 inhibitor nonsteroidal antiiflammatory drug, and lornoxicam, a nonspecific cyclooxygenase inhibitor, in rats. We wanted to test the hypothesis that preferential cyclooxygenase-2 inhibitors have a higher renal safety profile when compared with the nonspecific cyclooxygenase inhibitors. Materials and methods: Thirty healthy male Sprague-Dawley rats were included in the study. During the study period, 0.9% NaCl, 5.8 mg kg^{-1} meloxicam, or 1.3 mg kg^{-1} lornoxicam were given in 1 mL volumes once daily by the peritoneal route. On day 14, rats were placed in metabolic cages and their urine was collected for 24 h. After anesthesia was administered, blood samples were taken, followed by nephrectomy. Results: Serum sodium, potassium, creatinine, BUN, urine NAG (N-acetyl-beta-D-glucosaminidase), protein, and density values increased, while urine volume, sodium, potassium, creatinine values, and creatinine clearance decreased significantly in both groups when compared with the control. In the meloxicam group, serum potassium, BUN, and urine density values were greater than those of the lornoxicam group. In the lornoxicam group, serum sodium and urine NAG values were greater than those of the meloxicam group. Conclusion: We want to emphasize that meloxicam must be used with caution, similarly to nonspecific cyclooxygenase inhibitors.

Diesel Exhaust Particles in the Lung Aggravate Experimental Acute Renal Failure

Inhaled particles are associated with pulmonary and extrapulmonary effects. Also, acute renal failure (ARF) is associated with increased mortality, related to pulmonary complications. Here, we tested the possible potentiating effect of diesel exhaust particles (DEP) in an animal model of ARF induced by a single ip injection of cisplatin (CP, 6 mg/kg) in rats. Six days later, the rats were intratracheally instilled with either DEP (0.5 or 1 mg/kg) or saline (control) and renal, systemic, and pulmonary variables were studied 24 h thereafter. CP increased the serum concentrations of urea and creatinine and reduced glutathione (GSH) concentration and superoxide dismutase activity in renal cortex. CP caused renal tubular necrosis; increased urine volume, protein concentrations, and N-acetyl-beta-D-glucosaminidase (NAG) activity; and decreased urine osmolality. The combination of DEP and CP aggravated the CP-induced effects on serum urea and creatinine, urine NAG activity, and renal GSH. The arterial O(2) saturation and PO(2) were significantly decreased in CP + DEP versus CP + saline and CP + DEP versus DEP. The number of platelets was reduced in DEP compared to saline-treated rats and CP + DEP versus DEP alone or CP + saline. Increases in macrophage and neutrophils numbers in bronchoalveolar lavage were found in DEP versus saline group and CP + DEP versus CP. Histopathological changes in lungs of DEP-treated rats were aggravated by the combination of CP + DEP. These included marked interstitial cell infiltration and congestion. We conclude that the presence of DEP in the lung aggravated the renal, pulmonary, and systemic effects of CP-induced ARF.

Assessment of Novel Avian Renal Disease Markers for the Detection of Experimental Nephrotoxicosis in Pigeons (Columba livia)

Renal disease is a major cause of illness in captive and wild avian species. Current renal disease markers (e.g., uric acid, blood urea nitrogen, and creatinine) are insensitive. Two endogenous markers, creatine and N-acetyl-beta-D-glucosaminidase (NAG), were selected for study in the pigeon (Columba livia). Representative organs from four pigeons were surveyed to determine those exhibiting the highest level of each marker. In a separate study, NAG and creatine from plasma and urine were assayed before and after gentamicin (50 mg/kg twice daily), administration for up to 9 days. Observer-blinded pathologic scoring (five saline solution controls, 17 treated birds) was used to verify the presence of renal disease that corresponded to marker increases. The first study revealed that kidney tissue had the highest NAG activity (by approximately six times), and pectoral muscle had the most creatine (>900 times). In response to gentamicin, plasma creatine (>five times) and NAG increased (approximately six times), which paralleled uric acid (>10 times). Urine creatine (approximately 60 times) and NAG increased dramatically (approximately 50 times) in response to gentamicin. In conclusion, NAG, especially in the urine, may be of value to noninvasively detect renal toxin exposures and to monitor potentially nephrotoxic drugs, and might be of value to screen free-ranging birds in large exhibits or in the wild by assaying fresh urate samples at feeding stations.

Effect of Bicarbonate Administration on Cyclosporine-Induced Nephrotoxicity in Rats

Cyclosporine (CsA) is known to cause metabolic and distal tubular acidosis. There is some evidence that CsA reduces net HCO(3)(-) absorption. The aim of this study was to elucidate whether bicarbonate administration prevented CsA-induced functional or structural nephrotoxicity. Seven days after uninephrectomy, 20 rats were divided into 4 groups. NaHCO(3) (0.28 mol/L) was added in drinking water for 7 days, whereas control rats received regular tap water. The bicarbonate pretreated rats were administered either CsA (50 mg/kg intraperitoneally) or vehicle daily for a week. At the end of the procedure, animals were placed in metabolic cages for 24 hours after which we measured creatinine clearance (Ccr), urinary total proteins, pH, and N-acetyl-beta-D-glucosaminidase (NAG) activity. The kidney was fixed in formaldehyde. Ccr was significantly affected by the administration of CsA. The effects of CsA on serum pH and HCO(3)(-) concentration were prevented by pretreatment with NaHCO(3). However, it did not affect the CsA-induced increased urinary NAG activity or decreased Ccr. There was no protection of CsA-induced changes in renal tissues by NaHCO(3). Overall NaHCO(3) administration did not prevent CsA-induced changes in Ccr and NAG activity. These data suggested involvement of factors other than acid-base status in CsA-induced nephrotoxicity. However, correction of acidosis should still be considered for patients receiving CsA because acidosis exacerbates tissue damage.

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.

Biomarkers of exposure, effects and susceptibility in humans and their application in studies of interactions among metals in China

Biomonitoring employs three categories of biomarkers: Biomarkers of exposure, i.e. measurements of metal concentrations in a compartment in the body reflecting external or internal exposure; Biomarkers of effects include early as well as clinical effects. Biomarkers of susceptibility indicate individuals with increased sensitivity of target molecules or metabolism causing increased target dose. The three categories of biomarkers were used in studies of health effects of metal exposures in China. Adverse effects on the kidney tubules with increased levels of the effect biomarkers beta-2-microglobulin in urine (UB2M) and urinary N-acetyl-beta- d-glucosaminidase (UNAG) were found among Cd exposed population groups in China. Among persons exposed to Cd, occupationally or in the general environment, the level of Cd-induced metallothionein mRNA (MTmRNA) in peripheral lymphocytes appeared as a useful indicator of the ability of individuals to synthesize MT. Persons with low MTmRNA levels displayed higher biomarker values of renal tubular damage than persons with high levels of MTmRNA, at comparable levels of urinary Cd. Other studies demonstrated the importance of auto-antibodies against metallothionein in plasma (MTab) in modifying the response to Cd. Persons with high levels of MTab displayed tubular proteinuria at lower levels of urinary Cd than persons with low levels of MTab. Studies in two metal contaminated areas in China demonstrated clear interactions between Cd and inorganic arsenic. Combined exposure, with increased levels of As and Cd in urine, caused considerably higher biomarker values of renal tubular damage, measured as increased urinary levels of B2M or NAG, than each of the exposures alone.

Urinary Biomarkers in the Early Detection of Acute Kidney Injury after Cardiac Surgery

Serum creatinine (Scr) does not allow for early diagnosis of acute kidney injury (AKI). The diagnostic utility of urinary kidney injury molecule-1 (KIM-1), N-acetyl-beta-D-glucosaminidase (NAG), and neutrophil gelatinase associated lipocalin (NGAL) was evaluated for the early detection of postoperative AKI in a prospective study of 90 adults undergoing cardiac surgery. Designs, setting, participants, & measurements: Urinary KIM-1, NAG, and NGAL were measured at 5 time points for the first 24 h after operation and normalized to the urinary creatinine concentration after cardiac surgery. Receiver-operating characteristic curves were generated and the areas under the curve (AUCs) compared for performance of biomarkers in detection of postoperative AKI. Thirty-six patients developed AKI, defined as an increase in Scr of > or =0.3 mg/dl within 72 h after surgery. The AUCs for KIM-1 to predict AKI immediately and 3 h after operation were 0.68 and 0.65; 0.61 and 0.63 for NAG; and 0.59 and 0.65 for NGAL, respectively. Combining the three biomarkers enhanced the sensitivity of early detection of postoperative AKI compared with individual biomarkers: the AUCs for the three biomarkers combined were 0.75 and 0.78. The performance of combining biomarkers was even better among 16 early postoperative AKI patients with AUCs of 0.80 and 0.84, respectively. The results of this study support that a combination of urinary biomarkers may allow for early detection of postoperative AKI after cardiac surgery before a rise in Scr.

Role of Urinary Tubular Enzymes in Evaluation of Children With Ureteropelvic Junction Narrowing Under Conservative Management

To evaluate the role of urinary lysosomal enzyme N-acetyl-beta-D-glucosaminidase (NAG) and brush border enzymes alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) in the long-term follow-up of children under conservative management for ureteropelvic junction narrowing. The study included 30 children with dilated nonobstructed kidneys due to unilateral ureteropelvic junction narrowing who were treated conservatively and followed up for 15 months. Voided urine samples were obtained from the children at diagnosis and at 3, 9, and 15 months of follow-up. NAG, ALP, and GGT were measured in these urine samples. The conservative management of the children during their follow-up period revealed stabilization of renal function in 15 patients (dilated nonobstructed group) and deterioration in 15 (obstructed group). In patients considered to have dilated nonobstructed kidneys, a comparison between the mean values of urinary NAG, ALP, and GGT at the last follow-up and at baseline showed no significant differences. In addition, the mean values of glomerular filtration rate and split renal function showed no significant changes at the last follow-up examination compared with the basal condition. In patients considered to have obstructed kidneys, a comparison between the mean values of the 3 enzymes at diagnosis and at basal condition showed a significant increase in the 3 urinary biomarkers. Moreover, the mean values of the glomerular filtration rate and split renal function showed a significant reduction at diagnosis compared with the basal condition. NAG, ALP, and GGT are noninvasive biomarkers that could be used for long-term follow-up of children with ureteropelvic junction narrowing under conservative management to determine those who might develop obstruction.

Enzymuria determination in children treated with aminoglycosides drugs

Although aminoglycosides antibiotics are used in children and adult commonly, they have serious side effects such as nephrotoxicity and ototoxicity. In clinical practice, for renal function, the levels of serum creatinine and blood urea nitrogen routinely are measured. Since these parameters have limitations such as unreliability, insensitivity, and nonspecificity, the rapid assessment of renal function based on these patients is very important. Increase in N-acetyl-beta-D-glucosaminidase (NAG), a hydrolytic lysosomal enzyme, suggests proximal tubular cell damage. In this study, 32 children aged 2 months through 2 years, treated with gentamicin and amikacin for suspected infections at the pediatric ward of Alborz hospital from September 2006 to February 2007, were enrolled. Serum and fresh urine before and after drug infusion were obtained on the 1st, 3rd, and 5th days of antibiotic treatment. Serum urea and creatinine with urinary creatinine, albumin, NAG, lactate dehydrogenase (LDH) and alkaline phosphatase (AP) activity were then determined. A statistically significant increase in urinary NAG, LDH, and AP on 5th day was found compared with before gentamicin administration (P < 0.001, P < 0.01, P < 0.05, respectively). The urinary NAG activity may be a useful indicator of renal injury in children treated with aminoglycosides drugs compared with other routine clinical indicators.

Urinary Biomarkers for Sensitive and Specific Detection of Acute Kidney Injury in Humans

Acute kidney injury (AKI) is associated with high morbidity and mortality. The lack of sensitive and specific injury biomarkers has greatly impeded the development of therapeutic strategies to improve outcomes of AKI.The unique objective of this study was to evaluate the diagnostic performance of nine urinary biomarkers of AKI-kidney injury molecule-1 (KIM-1), neutrophil gelatinase associated lipocalin (NGAL), interleukin-18 (IL-18), hepatocyte growth factor (HGF), cystatin C (Cys), N-acetyl-beta-D-glucosaminidase (NAG), vascular endothelial growth factor (VEGF), chemokine interferon-inducible protein 10 (IP-10; CXCL10), and total protein-in a cross-sectional comparison of 204 patients with or without AKI.Median urinary concentrations of each biomarker were significantly higher in patients with AKI than in those without AKI (p < 0.001). The area under the receiver operating characteristics curve (AUC-ROC) for the combination of biomarkers using a logic regression model [risk score of 2.93*(NGAL > 5.72 and HGF > 0.17) + 2.93*(PROTEIN > 0.22) -2*(KIM < 0.58)] was greater (0.94) than individual biomarker AUC-ROCs. Age-adjusted levels of urinary KIM-1, NAG, HGF, VEGF, and total protein were significantly higher in patients who died or required renal replacement therapy (RRT) when compared to those who survived and did not require RRT.Our results demonstrate the comparative value of multiple biomarkers in the diagnosis and prognosis of AKI.

Effect of Renin-Angiotensin-Aldosterone System Inhibition, Dietary Sodium Restriction, and/or Diuretics on Urinary Kidney Injury Molecule 1 Excretion in Nondiabetic Proteinuric Kidney Disease: A Post Hoc Analysis of a Randomized Controlled Trial

Tubulointerstitial damage plays an important role in chronic kidney disease (CKD) with proteinuria. Urinary kidney injury molecule 1 (KIM-1) reflects tubular KIM-1 and is considered a sensitive biomarker for early tubular damage. We hypothesized that a decrease in proteinuria by using therapeutic interventions is associated with decreased urinary KIM-1 levels. Post hoc analysis of a randomized, double-blind, placebo-controlled, crossover trial. 34 proteinuric patients without diabetes from our outpatient renal clinic. Stepwise 6-week interventions of losartan, sodium restriction (low-sodium [LS] diet), their combination, losartan plus hydrochlorothiazide (HCT), and the latter plus an LS diet. Urinary excretion of KIM-1, total protein, and N-acetyl-beta-d-glucosaminidase (NAG) as a positive control for tubular injury. Mean baseline urine protein level was 3.8 +/- 0.4 (SE) g/d, and KIM-1 level was 1,706 +/- 498 ng/d (increased compared with healthy controls; 74 ng/d). KIM-1 level was decreased by using placebo/LS (1,201 +/- 388 ng/d; P = 0.04), losartan/high sodium (1,184 +/- 296 ng/d; P = 0.09), losartan/LS (921 +/- 176 ng/d; P = 0.008), losartan/high sodium plus HCT (862 +/- 151 ng/d; P = 0.008) and losartan/LS plus HCT (743 +/- 170 ng/d; P = 0.001). The decrease in urinary KIM-1 levels paralleled the decrease in proteinuria (R = 0.523; P < 0.001), but not blood pressure or creatinine clearance. 16 patients reached target proteinuria with protein less than 1 g/d, whereas KIM-1 levels normalized in only 2 patients. Urinary NAG level was increased at baseline and significantly decreased during the treatment periods of combined losartan plus HCT only. The decrease in urinary NAG levels was not closely related to proteinuria. Post hoc analysis. Urinary KIM-1 level was increased in patients with nondiabetic CKD with proteinuria and decreased in parallel with proteinuria by using losartan, sodium restriction, their combination, losartan plus HCT, and the latter plus sodium restriction. These results are consistent with the hypothesis of amelioration of proteinuria-induced tubular damage. Long-term studies are warranted to evaluate whether targeting treatment on KIM-1 can improve outcomes in patients with CKD with proteinuria.

Serum cystatin C level for better assessment of glomerular filtration rate in cystic fibrosis patients treated by amikacin

Monitoring of renal function in cystic fibrosis (CF) patients is essential. The dosage regimen of amikacin is regularly modified according to the patient's glomerular filtration rate (GFR). The aim of the study was to evaluate the use of cystatin C (CyC) for monitoring amikacin therapy along with other markers of renal tubular and glomerular function, and damage [N-acetyl-beta-d glucosaminidase (NAG), creatinine level and creatinine clearance]. We compared the GFR, estimated from the serum concentrations of creatinine (Cockcroft-Gault formula) and CyC (Grubb's formula). Seventy-one patients (mean age 12 years; range 4-28 years) with CF were treated by intermittent intravenous infusion of amikacin. Tubular nephrotoxicity was investigated by measurement of urine NAG/urine creatinine ratio (U-NAG/U-creatinine). Concentrations of all markers were measured before starting amikacin therapy and at days 3, 5, 7, 10 and 12. Fluorescence polarization analysis, turbidimetry, enzymatic phototometric creatinine deaminase method and fluorimetry were used for determination of serum amikacin, serum CyC, creatinine and urine NAG activity. Receiver operating characteristic (ROC) analysis was performed to assess the influence of GFR estimated from serum creatinine and serum CyC for the prediction of amikacin clearance during aminoglycoside therapy. Significant differences in the rate of U-NAG/U-creatinine were noted before and after treatment with amikacin (P < 0.001). Serum creatinine levels and creatinine clearance at the end of amikacin therapy (12th day) did not show any significant differences in comparison with the levels measured before the start of therapy (0th day). At days 5, 7, 10 and 12, serum CyC levels showed a significant elevation (P < 0.001), and CyC clearance showed a significant decrease (P < 0.001) in comparison with the levels measured at day 0. The ratio of amikacin clearance/creatinine clearance decreased with therapy whereas the amikacin clearance/CyC and amikacin clearance/CyC clearance increased. We showed that the rate of U-NAG/U-creatinine is a suitable marker for monitoring tubular nephrotoxicity in CF patients. Serum creatinine and estimated creatinine clearance are modest predictors of GFR in CF patients. CyC appears to be a better marker of GFR than serum creatinine concentration or creatinine clearance in our study. Serum CyC levels and CyC clearance showed greater ability to predict amikacin clearance during therapy than creatinine clearance.

Prognostic values of serum cystatin C and β2 microglobulin, urinary β2 microglobulin and N-acetyl-β-D-glucosaminidase in early acute renal failure after liver transplantation

Acute renal failure (ARF) after liver transplantation is associated with high mortality and morbidity. Early therapeutic or preventive intervention is hampered by the lack of early effective prognostic factors. Recent studies indicated that serum levels of cystatin C and beta2-microglobulin (beta2 MG) as well as urinary beta2 MG and N-acetyl-beta-D-glucosaminidase (NAG) would increase in patients with early and mild renal impairment. In this study, these factors were detected during the different stages in patients who accepted orthotopic liver transplantation (OLT), and their feasibilities to predict early ARF after OLT were also analyzed. Sixty patients with normal blood urea nitrogen (BUN) and serum creatinine (SCr) who received modified piggyback liver transplantation without veno-venous bypass were prospectively studied. Blood samples were drawn from patients for the determination of serum beta2 MG (n = 60), SCr (n = 60) and serum Cystatin C (n = 39) at following 5 intervals: before operation (T0), 20 minutes before anhepatic phase (T1), 25 minutes in anhepatic (T2), 60 minutes after reperfusion (T3) and at the end of operation (T4). Urinary beta2 MG (n = 60) and NAG (n = 60) were also examined at following 3 intervals: before operation (T0), 60 minutes after reperfusion (T3) and at the end of operation (T4). According to the Rimola A criteria of ARF in 24 hours after operation, all the patients were divided into two groups: ARF group and non-ARF group. The data were statistically analyzed to evaluate the feasibiliy of regarding these factors as prognostic factors for early ARF after liver transplantation in patients with normal SCr and BUN before operation. Ten of sixty cases showed ARF (16.7%). The Logistic regression analysis showed that the levels of serum and urinary beta2 MG as well as serum cystatin C before operation were correlated with early ARF after liver transplantation (P < 0.05), while only serum levels of cystatin C and Cr at the end of operation correlated with early ARF (P < 0.05, P < 0.01) after liver transplantation. The serum beta2 MG, Cystatin C, SCr and urinary beta2 MG levels in ARF group were much more higher than that in non-ARF group (P < 0.05, P < 0.01). There were significant differences between the correct and false predictive positive ratios of serum cystatin C, serum and urinary beta2 MG levels before operation (P < 0.05, P < 0.01), while only SCr showed significant difference between these groups at the end of operation (P < 0.01). The results revealed that there was potential renal damage among those patients who demonstrated normal SCr and BUN before operation, and that liver transplantation could aggravate this damage and causing ARF. Here we provided the prognostic values of serum Cystatin C, beta2 MG, urinary beta2 MG and NAG in patients with early acute renal failure after liver transplantation.

Estimation of Benchmark Dose for Bone Damage and Renal Dysfunction in a Chinese Male Population Occupationally Exposed to Lead

The aim of this study was to examine a possible relationship between lead nephropathy and its effects on the skeleton in male population occupationally exposed to lead in China. One hundred and fifty-five lead-exposed male workers in a storage battery plant in Shanghai were selected as the exposed subjects while the 36 healthy male officers in the plant who were not occupationally exposed to lead were treated as the control. Blood lead (BPb) and urine lead were used as biomarkers for exposure. Z score, urine hydroxyproline (HYP), serum alkaline phosphatase (bone isoenzyme) (BALP) and serum osteocalcin (BGP) were used as biomarkers for bone effects. Urine N-acetyl-beta-D-glucosaminidase (UNAG) and urine albumin (UALB) were applied as biomarkers of renal tubular and glomerular dysfunction. Bone mineral density was measured by the monophoton absorptiometry (SPA-4). It was found that there were linear correlate relationships between lead exposure and NAG, ALB, BALP, BGP, HYP, Z score (P < 0.01), after controlling confounders such as age and work year. NAG, ALB, BALP, BGP and HYP would increase with the increase of lead exposure. Z score would decrease with the increase of lead exposure. Of 21 subjects with osteoporosis, nine subjects were suffering from renal dysfunction. The prevalence of renal dysfunction (42.86%) was significantly higher in the subjects with osteoporosis than in those without osteoporosis (17.65%) (chi(2) = 7.310, P = 0.007). The prevalence of osteoporosis had relationship with renal tubular damage, but not with renal glomerular damage. This showed that glomerular dysfunction plays a smaller role than tubular dysfunction in the causation of bone damage. Benchmark dose in terms of BPb was calculated using Benchmark Dose Software Version 1.3.2 software. The benchmark dose lower limit of a one-sided 95% confidence interval (BMDL) for 10% excess risk was also determined. It was found that BMDL(-05) for BALP, UNAG, BGP, HYP, Z score and UALB of BPb increased sequentially. The BMDL values for UNAG (10.13 microg dL(-1)) were lower than those of Z score (14.17 microg dL(-1)). The present study has thus demonstrated the combined adverse effects (osteoporosis and renal dysfunction) caused by occupational exposure to lead. There was a dose-response relationship between lead exposure and prevalence of osteoporosis, renal dysfunction and bone metabolism. The renal dysfunction might develop earlier than osteoporosis. Osteoporosis caused by lead was related to the change of bone metabolism and renal dysfunction, which was especially to tubular damage but not to glomerular damage.

Preventive and therapeutic effects of Yishen Huanji Decoction on kidney injury in rats induced by simulation of military overtraining

To observe the preventive and therapeutic effects of Yishen Huanji Decoction (YSHJD), a compound traditional Chinese herbal medicine, on military overtraining-induced kidney injury in a rat model. Thirty SD rats were randomly divided into normal control group, untreated group and YSHJD-treated group. The military overtraining-induced kidney injury in rats was established by forcing to run on the treadmill for 8 weeks. The rats in YSHJD-treated group were administered with YSHJD at the same time. The 24-hour urines were collected every weekend for detecting the contents of urinary sediment, 24-hour urine total protein, 24-hour urine albumin and activity of N-acetyl-beta-D-glucosaminidase (NAG). The blood and renal tissues were collected after 8-week training, and the levels of serum urea nitrogen (BUN) and creatinine (SCr) were detected. Angiotensin II (Ang II) was detected by radioimmunoassay and activity of Na(+), K(+)-ATPase in kidney was analyzed by chemical colorimetric method. Compared with the normal control group, after 8-week training, the contents of 24-hour urine protein, activities of NAG in urine, and the levels of BUN and SCr in rats in the untreated group and YSHJD-treated group were obviously increased (P<0.05), and these parameters of the YSHJD-treated group were lower than those of the untreated group (P<0.05). The contents of Ang II in blood plasma and kidney of rats in the untreated group and YSHJD-treated group were higher than those of the normal control group (P<0.05), and had no statistical difference between the untreated group and YSHJD-treated group. Compared with the normal control group, the activity of Na(+), K(+)-ATPase in kidney of rats in the untreated group was obviously decreased (P<0.05), and had no statistical difference between the normal control group and YSHJD-treated group. YSHJD can protect against military overtraining-induced kidney injury in rats by decreasing the contents of 24-hour urine protein, BUN and SCr, and the activity of NAG, and increasing the activity of Na(+), K(+)-ATPase.

Early markers of renal dysfunction in patients with beta-thalassemia major

Studies of renal involvement in thalassemia syndromes have been varied and few. The most important cause of mortality and morbidity in these patients is organ failure due to iron deposition. We report here a cross-sectional study carried out between February 2005 and February 2006 on all beta-thalassemia major patients being treated in Mofid Children's hospital, Tehran. The aim of the study was to detect renal dysfunction in these patients. The patient cohort consisted of 103 patients with various disease severities. Fresh first morning urine samples were collected and analyzed for sodium (Na), potassium (K), calcium (Ca), creatinine (Cr), phosphate, uric acid (UA), N-acetyl beta-D-glucosaminidase (NAG) and amino acids. We also carried out a complete blood count evaluation and assayed fasting blood sugar and serum ferritin, sodium, potassium, creatinine, uric acid and amino acids in all patients. The mean age of our patient cohort was 12.5+/-5.53 years and 53.4% were female. Abnormal levels of urinary NAG were detected in 35.9% of patients (confidence interval 26-45%). Abnormal levels of fractional excretion (FE)-Na, FE-K and FE-UA and abnormal urine protein Pr/Cr and urine Ca/Cr ratios were present in 29.1, 7.8, 52.4, 0.3 and 22.3% of the patients, respectively. There was a significant relationship between urinary NAG and the age of the patient (R=0.35), duration of deferoxamine therapy (R= 0.31), duration of receiving blood transfusions (R=0.34) and level of fasting blood sugar (R=0.2). We concluded that renal disorders are not rare in patients with beta-thalassemia major and that they may increase in terms of frequency with age, increased duration of transfusion and deferoxamine usage and high levels of blood sugar.

Renal magnesium wasting and tubular dysfunction in leptospirosis

Tubulo-interstitial nephritis is the main cause of acute renal injury in leptospirosis. The aim of this study was to evaluate renal tubular function and excretion of solutes in leptospirosis patients during a recent outbreak of leptospirosis in Nan province, Thailand. Clinical manifestations were recorded and routine laboratory tests were performed upon admission. Renal tubular functions including tubular reabsorption of phosphate (TRP), fractional excretion of magnesium (FE(Mg)), urinary calcium to creatinine ratio (Uca/cr), urine N-acetyl-beta-D glucosaminidase (NAG) and urine beta(2)-microglobulin were serially monitored during 2 weeks after admission. A total of 20 leptospirosis patients were recruited. Nine (45%) patients had acute renal failure (ARF). Increased urine NAG and beta(2)-microglobulin, which indicate proximal tubular dysfunction, were demonstrated in all 20 (100%) patients. Fifteen (75%) patients had hypermagnesuria, whereas 10 (50%) patients had decreased TRP. Renal magnesium (Mg) and phosphate (P) wasting caused hypomagnesaemia and hypophosphataemia in nine and three patients with ARF, respectively. These abnormal findings significantly improved within 2 weeks after admission. We conclude that renal Mg and P wasting commonly occur in patients with leptospirosis. The measurement of Mg and P levels in both serum and urine of leptospirosis patients, especially those with ARF, is therefore highly recommended.

Benchmark dose approach for renal dysfunction in workers exposed to lead

Benchmark dose (BMD) and the lower confidence limit on the benchmark dose (BMDL) of blood lead were estimated to explore the biologic exposure limits for renal dysfunction caused by lead. One hundred thirty-five workers from one storage battery plant were selected as lead exposure group while 143 mechanics as the control. The relationship between the blood lead concentration and the urinary excretion of total protein (TP), beta2-microglobulin (beta2-MG), and N-acetyl-beta-D-glucosaminidase (NAG) was studied. The quantal linear logistic regression model (BMDS Version 1.3.1) was used to calculate BMD and BMDL of blood lead. The results showed that the levels of NAG, beta2-MG, and TP in lead-exposed workers were higher than those of control group and elevated along with rising length of employment. The levels of three indices for renal dysfunction increased with the elevated blood lead. The BMD and BMDL of blood lead for renal dysfunction were from 299.4 to 588.7 microg/L and from 253.4 to 402.3 microg/L, respectively. The BMDL of blood lead was ranged from high to low as TP, beta2-MG, and NAG. It is suggested that the urinary NAG activity could be a sensitive and early biomarker of renal tubular dysfunction induced by lead. When assessing renal function in workers occupationally exposed to lead, a blood lead level of 250 microg/L could serve as a warning signal.

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

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. 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. 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). 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.

Urinary N-Acetyl-β-D-Glucosaminidase Levels in Patients with Laryngeal Squamous Cell Carcinoma

Tumour markers play an important role in the diagnosis of cancer and the early detection of recurrences during follow-up. This study aimed to assess the clinical value of measuring urinary N-acetyl-beta-d-glucosaminidase (U-NAG) levels in patients with laryngeal squamous cell carcinoma. Prospective, controlled study. Tertiary university hospital. Our study included 21 patients with primary laryngeal squamous cell carcinoma and 17 cases with recurrent laryngeal squamous cell carcinoma. U-NAG levels of patients with tumours at different stages were compared with a control group of 19 healthy individuals with no known cancer. Patients' age, TNM stage, blood urea, glucose, alanine aminotransferase (ALT), and U-NAG. A statistically significant difference was found between U-NAG levels of patients with a primary tumour (preoperative period) and the control group (one-way analysis of variance, p = .00; Dunnett's t-test, p = .00). In the postoperative period, the observed trend was that of a significant decrease among primary cases (paired t-test, p = .00). U-NAG levels of patients with a recurrent tumour and patients with a primary tumour (preoperative period) were not significantly different (Tukey honest significant difference test, p = .841). There was no statistically significant difference for blood urea (t = -1.95, p = .064), glucose (t = -1.84, p = .074), or ALT (t = -1.79, p = .080). No significant relationship was found between the TNM stage and preoperative U-NAG levels (p > .05). These results suggest that U-NAG might be used in the diagnosis of laryngeal carcinoma and the early detection of recurrences during follow-up. Further investigations are warranted to clarify the prognostic significance of U-NAG levels.