Untypically mild phenotype of a patient suffering from Sanfilippo syndrome B with the c.638C>T/c.889C>T (p.Pro213Leu/p.Arg297Ter) mutations in the NAGLU gene.

BACKGROUND: Sanfilippo syndrome B (or mucopolysaccharidosis type IIIB [MPS IIIB]) is a severe inherited metabolic disorder caused by mutations in the NAGLU gene, encoding α-N-acetylglucosaminidase. Dysfunction of this enzyme results in impaired degradation of heparan sulfate, one of glycosaminoglycans, and accumulation of this complex carbohydrate in lysosomes. Severe symptoms occurring in this disease are related to progressive neurodegeneration and include extreme hyperactivity, sleeping problems, aggressive-like behavior, reduced fear, and progressive mental and cognitive deterioration. No cure is currently available for Sanfilippo disease. METHODS: Clinical characterization of the patient's symptoms has been performed. Biochemical analyses included glycosaminoglycan level determination and measurement of α-N-acetylglucosaminidase activity. Molecular analyses included exome sequencing and detailed analysis of the NAGLU gene. Psychological tests included assessment of attention, communication and behavior. RESULTS: We describe a patient with an untypically mild phenotype, who was diagnosed at the age of 13 years. Many cognitive, communication, and motoric functions were preserved in this patient, contrary to vast majority of those suffering from MPS IIIB. The patient is a compound heterozygote (c.638C>T/c.889C>T) in the NAGLU gene, and relatively high residual activity (about 25%) of α-N-acetylglucosaminidase was measured in serum (while no activity of this enzyme could be detected in dry blood spot). CONCLUSIONS: We suggest that the mild phenotype might arise from the partially preserved function of the mutant enzyme (p.Pro213Leu), suggesting the genotype-phenotype correlation in this case.

Rhubarb and Astragalus Capsule Attenuates Renal Interstitial Fibrosis in Rats with Unilateral Ureteral Obstruction by Alleviating Apoptosis through Regulating Transforming Growth Factor beta1 (TGF-ß1)/p38 Mitogen-Activated Protein Kinases (p38 MAPK) Pathway.

BACKGROUND Rhubarb and astragalus capsule (RAC) has been used in the clinical treatment of chronic kidney disease for decades. However, the mechanism of RAC has not been fully elucidated. This study aimed to investigate the protective effect and mechanisms of RAC on unilateral ureteral obstruction (UUO)-induced renal interstitial fibrosis. MATERIAL AND METHODS The main components of RAC are detected by high-performance liquid phase (HPLC). A rat model of UUO was established, and a subset of rats underwent treatment with RAC. Renal function and renal pathology were examined at 14 days and 21 days after the UUO operation. Renal cell apoptosis was detected by TUNEL staining. The levels of Bcl-2 and Bax in the kidney were examined by western blotting, and the levels of collagen I, alpha-SMA, transforming growth factor (TGF)-ß1, and p38 MAPK in the kidneys were detected by immunohistochemistry. RESULTS High-performance liquid phase chromatography showed that RAC contained 1.12 mg/g aloe-emodin, 2.25 mg/g rhein, 1.75 mg/g emodin, and 4.50 mg/g chrysophanol. Administration of RAC significantly decreased the levels of urinary N-acetyl-ß-D-glucosaminidase (NAG), serum blood urea nitrogen (BUN), and creatinine (Scr) and also reduced renal tissue damages and interstitial fibrosis induced by UUO in rats. Moreover, the increased levels of collagen I, alpha-SMA, TGF-ß1, p38 MAPK, and the Bax/Bcl-2 ratio, as well as cell apoptosis in the kidney, were induced by UUO, and were all found deceased by RAC treatment. CONCLUSIONS RAC can improve the renal interstitial fibrosis induced by UUO, and the mechanism may be related to inhibition of renal tubular cell apoptosis via TGF-ß1/p38 MAPK pathway.

Carbon dots as fluorescent nanoprobe for the determination of N-acetyl-ß-d-glucosaminidase activity.

Carbon dots (CDs) were synthesized from p-aminophenol and ethylenediamine via one-step under mild condition and used as a sensitive fluorescent nanoprobe for the activity determination of N-acetyl-ß-d-glucosaminidase (NAG). In this assay, p-nitrophenol was in situ produced from p-nitrophenyl-ß-D-N-acetyl-glucosaminide, which was exclusively hydrolyzed by NAG. The UV absorption peak of p-nitrophenol (maximum at 400 nm) overlapped the excitation peak of CDs with maximum wavelength at 415 nm, which caused the fluorescence decline of CDs based on inner filter effect. The activity of NAG was determined by the fluorescence changes. The assay is highly sensitive to NAG with a low detection limit of 0.75 U L-1 (K = 3) and showed a good linear relationship in the range from 1 to 45 U L-1. This CDs nanoprobe was successfully applied for the determination of NAG activity in human serum and urine samples.

N-acety-b-D-glucosaminidase: A potential biomarker for early detection of acute kidney injury in acute chest pain.

AIM: Acute kidney injury (AKI) is often underdiagnosed due to several limitations of the renal marker creatinine. Tubular urinary biomarkers may substantially contribute to diagnose AKI early. For early detection of AKI, we evaluated for the first time N-acetyl-ß-d-glucosaminidase (NAG), Kidney-injury-molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) in acute chest pain. METHODS: We included 402 chest pain patients aged 18 to 95 years seen in the emergency department. From 311 subjects, blood and urine samples were collected. RESULTS: Thirty-three patients developed an AKI and showed a significant increase in all three tubular markers compared to patients without AKI (each P < .001). According to receiver operating characteristic (ROC) analysis, combining NAG and creatinine showed a significantly increased area under the curve (AUC) compared to creatinine alone (AUC: 0.75 vs 0.87; P < .001). KIM-1, NGAL and cystatin C showed no significant differences in AUC compared to creatinine. In 120 individuals with blood and urine sampling before contrast media exposure, ROC analysis showed a significantly improved diagnostic performance for the combination of both (AUC: 0.83 vs creatinine AUC: 0.66; P = .004). AKI occurrence showed no dependency from CM volume. NAG presented as an independent AKI predictor beside creatinine, age, the diagnosis of myocardial infarction and mean arterial pressure. Regarding the prognostic value for renal replacement therapy, the combination of NAG and creatinine showed a significantly lager AUC than creatinine (AUC: 0.95 vs AUC: 0.85; P < .001). CONCLUSION: NAG presented as a promising marker of impending AKI and the necessity of renal replacement therapy.

Early Prediction of Graft Outcomes After Kidney Transplantation From Donors After Circulatory Death: Biomarkers and Transplantation Characteristics.

BACKGROUND: This study aimed to identify transplantation characteristics and biomarkers that predict outcomes for kidney transplant (KT) patients from donors after circulatory death (DCDs). METHODS: Consecutive patients receiving a KT from a DCD in our center between 2014 and 2016 were included; the reference population was recipients with a living donor KT. The urinary tubular injury biomarker-to-creatinine ratio and serum lactate dehydrogenase (LDH) were measured at post-transplant days 1 and 3. The primary outcome was the occurrence of delayed graft function (DGF). Descriptive and receiver operating characteristic analyses were performed. RESULTS: Forty-one patients were included in the analysis: 15 (36.59%) DCD KTs (9 of which suffered from DGF) and 26 (63.41%) living donor KTs. For the primary endpoint, neutrophil gelatinase-associated lipocalin, N-acetyl-beta-D-glucosaminidase, urinary tubular injury biomarker-to-creatinine ratio, and LDH areas under the curve were 1 and 0.96 (95% confidence interval: 0.84-1.0), 1 and 0.92 (95% confidence interval: 0.73-1.0), respectively. Among the transplant characteristics, only the 30-minute resistive index on the perfusion machine was significantly higher in DCD KTs with DGF vs those without DGF (0.26 mm Hg/mL/min [0.20; 0.32] vs 0.14 mm Hg/mL/min [0.12; 0.16], P = .05). Median 3-month creatinine clearance among DGF DCD KTs was 49 mL/min/1.73 m2 [IQR: 42; 65] and 65 mL/min/1.73 m2 [IQR: 62; 66] among DCD KTs without DGF (P = .22). CONCLUSION: In the DCD KT population, clinical and biological markers were identified that provided predictive tools for DGF. Thus, systematic measurement of these biomarkers, particularly LDH, could improve the management of kidney graft recipients' immunosuppressive therapy.

A Renal-Clearable Duplex Optical Reporter for Real-Time Imaging of Contrast-Induced Acute Kidney Injury.

Despite its high morbidity and mortality, contrast-induced acute kidney injury (CIAKI) remains a diagnostic dilemma because it relies on in vitro detection of insensitive late-stage blood and urinary biomarkers. We report the synthesis of an activatable duplex reporter (ADR) for real-time in vivo imaging of CIAKI. ADR is equipped with chemiluminescence and near-infrared fluorescence (NIRF) signaling channels that can be activated by oxidative stress (superoxide anion, O2.- ) and lysosomal damage (N-acetyl-ß-d-glucosaminidase, NAG), respectively. By virtue of its high renal clearance efficiency (80 % injected doses after 24 h injection), ADR detects sequential upregulation of O2.- and NAG in the kidneys of living mice prior to a significant decrease in glomerular filtration rate (GFR) and tissue damage in the course of CIAKI. ADR outperforms the typical clinical assays and detects CIAKI at least 8 h (NIRF) and up to 16 h (chemiluminescence) earlier.

N-acetylcysteine suppresses colistimethate sodium-induced nephrotoxicity via activation of SOD2, eNOS, and MMP3 protein expressions.

OBJECTIVE: To investigate the molecular mechanisms of colistimethate sodium-induced nephrotoxicity and the protective effect of N-acetylcysteine (NAC) against nephrotoxicity. METHODS: Twenty-eight Wistar rats were divided into four groups comprised of control, colistin, NAC, and colistin-NAC co-treatment, respectively. Serum creatinine and urine N-acetyl-ß-d-glucosaminidase (NAG) levels were measured at different time intervals. Histological changes, apoptosis, total oxidant and antioxidant status, and the expression levels of endothelial nitric oxide synthase (eNOS), superoxide dismutase 2 (SOD2), and matrix metalloproteinase 3 (MMP3) were evaluated in renal tissue. RESULTS: In the colistin group, post-treatment creatinine levels were higher than pretreatment levels (p = .001). There was a significant increase in urine NAG level following colistin treatment on day 10, compared to the baseline value and the first day of treatment (p = .001 and .0001, respectively). Urine NAG levels were higher in the colistin group on the 10th day of treatment than in the other groups (p < .01). Colistin treatment increased the apoptosis index and renal histological damage score (RHDS) significantly and these changes were reversed in NAC co-treatment (RHSD and apoptosis index were 45 and 0 for sterile saline group, 29 and 2 for NAC group, 122 and 7 for colistin group, and 66 and 2 for colistin + NAC group). We observed no difference between groups regarding total antioxidant and total oxidant status in the kidneys. The expression levels of eNOS, SOD2, and MMP3 decreased significantly in the kidneys of colistin-treated rats; these changes were reversed in the kidneys of NAC co-treated rats. CONCLUSIONS: N-acetylcysteine prevented colistin-induced nephrotoxicity through activation of expression levels of SOD2, eNOS, and MMP3.

Tissue Indices of Telomere Length and p53 in Patients with Different Gastrointestinal Tumors: Correlation with Clinicopathological Status.

Telomere length dysfunction is involved in the generation of genomic rearrangements that drive progression to malignancy. A set of serological markers for telomere dysfunction, namely chitinase and N-acetylglucosaminidase (NAG), DNA damage, and tissue alteration of p53 have been identified. The probability that genomic damage, accumulation of reactive oxygen species, and shorter telomeres may be related to the onset and advancement of gastrointestinal (GI) tumors. A total of 40 patients with GI tumors and 20 healthy controls with matched age and sex were included. Estimation of serum chitinase, NAG, lipid peroxide (LPER), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase by colorimetric methods, and p53 by ELISA were assessed. Related clinicopathological features were determined. Serological chitinase, NO, LPER, and p53 were significantly increased, SOD was significantly decreased (p Ë‚ 0.001 for each) in GI tumor patients compared with controls and correlated significantly with age. There was a significant correlation between telomere dysfunction indices, p53, oxidative stress indices, and malignant stages of GI cancer patients. Moreover, a significant difference in the mean serum levels of indices between control, malignant, and benign subjects was found. Accordingly, these biomarkers play an important role in the pathogenesis of GI cancer and their estimation may predict the GI tumor behavior.

Modest Impact of Serial Measurements of Acute Kidney Injury Biomarkers in an Adult Intensive Care Unit.

BACKGROUND/AIMS: Acute kidney injury (AKI) biomarkers have been developed with the aim of being able to detect kidney damage earlier than the detection process based on serum creatinine levels. However, single time-point measurements appear to furnish insufficient information for detecting and predicting AKI in intensive care unit patients who are frequently affected by multiple and transient/persistent renal insults. We evaluated whether serial measurements enable the prediction of AKI outcomes in such patients. METHODS: Serial measurements of AKI biomarkers, including plasma and urinary neutrophil gelatinase-associated lipocalin, urinary L-type fatty acid-binding protein, and urinary N-acethyl-ß-D-glucosaminidase, at intensive care unit (ICU) admission (d1) and 24 h later (d2) were performed for critically ill adult patients in a mixed ICU. We assessed whether each biomarker could predict newly developed AKI, recovery from AKI, worsening of AKI, and hospital mortality. RESULTS: Among the enrolled 272 patients, 33 were determined to show newly developed AKI after ICU admission, 58 showed worsening of AKI, 57 recovered from AKI, and 38 died in the hospital. ROC analysis showed that biomarkers at day 2 provided no significant additional benefit in predicting the above-mentioned AKI outcomes compared with those at day 1. However, net reclassification improvement analysis demonstrated that adding day 2 biomarkers to the clinical model comprising clinical variables along with day 1 biomarkers significantly improved the prediction of these AKI outcomes. CONCLUSION: Serial measurement of AKI biomarkers used in clinical models could contribute to the prediction of AKI outcomes in a heterogeneous cohort of adult mixed ICU patients, although its reliability seemed to be modest.

Newborn screening for mucopolysaccharidoses: a pilot study of measurement of glycosaminoglycans by tandem mass spectrometry.

BACKGROUND: Mucopolysaccharidoses (MPS) are a group of inborn errors of metabolism that are progressive and usually result in irreversible skeletal, visceral, and/or brain damage, highlighting a need for early diagnosis. METHODS: This pilot study analyzed 2862 dried blood spots (DBS) from newborns and 14 DBS from newborn patients with MPS (MPS I, n = 7; MPS II, n = 2; MPS III, n = 5). Disaccharides were produced from polymer GAGs by digestion with chondroitinase B, heparitinase, and keratanase II. Heparan sulfate (0S, NS), dermatan sulfate (DS) and mono- and di-sulfated KS were measured by liquid chromatography tandem mass spectrometry (LC-MS/MS). Median absolute deviation (MAD) was used to determine cutoffs to distinguish patients from controls. Cutoffs were defined as median + 7× MAD from general newborns. RESULTS: The cutoffs were as follows: HS-0S > 90 ng/mL; HS-NS > 23 ng/mL, DS > 88 ng/mL; mono-sulfated KS > 445 ng/mL; di-sulfated KS > 89 ng/mL and ratio di-KS in total KS > 32 %. All MPS I and II samples were above the cutoffs for HS-0S, HS-NS, and DS, and all MPS III samples were above cutoffs for HS-0S and HS-NS. The rate of false positives for MPS I and II was 0.03 % based on a combination of HS-0S, HS-NS, and DS, and for MPS III was 0.9 % based upon a combination of HS-0S and HS-NS. CONCLUSIONS: Combination of levels of two or more different GAGs improves separation of MPS patients from unaffected controls, indicating that GAG measurements are potentially valuable biomarkers for newborn screening for MPS.

Serum and urinary biomarkers that predict hepatorenal syndrome in patients with advanced cirrhosis.

BACKGROUND: Prediction of hepatorenal syndrome (HRS) remains difficult in advanced cirrhotic patients. AIMS: To evaluate use of serum and urine biomarkers to predict HRS. METHODS: We prospectively recruited Child's B or C cirrhotic patients with normal serum creatinine, and followed them for 12 weeks for the development of HRS. Serum Cystatin C (CysC), serum and urine Neutrophil Gelatinase-Associated Lipocalin (NGAL), serum and urine IL-18, serum N-acetyl-ß-d glucosaminidase (NAG), urine kidney injury molecule-1 (KIM-1) and urine liver-type fatty acid binding protein (LFABP) were measured at recruitment (baseline), and their relationship with subsequent HRS investigated. RESULTS: 43 patients were included. 12 (27.9%) developed HRS at 7.3±5.1 weeks from baseline. Logistic regression analysis showed that baseline urinary NGAL and urinary KIM-1 were significantly associated with the development of HRS (RR 1.007, 95% CI 1.001-1.012, p=0.014; RR 1.973, 95% CI 1.002-3.886, p=0.049). The cut-off values for NGAL and KIM-1 to predict HRS were 18.72ng/mL and 1.499ng/mL respectively (AUCs 0.84, p=0.005; and 0.78, p=0.008). CONCLUSION: Urinary NGAL and KIM-1 could serve as biomarkers to predict HRS in advanced cirrhotic patients.

Urinary kidney injury molecules in children with febrile seizures.

OBJECTIVE: Hypoxia occurs following convulsions, and hypoxia is one of the most common causes of acute renal damage. The aim of this study was to investigate urinary levels of kidney injury molecules, including neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-ß-D-glucosaminidase (NAG), and liver-type fatty acid-binding protein (L-FABP) in children with febrile seizures (FS) for the first time. METHODS: The study included 28 children with FS and 34 age and gender matched healthy children. Serum biochemistry and blood gases were measured in the serum samples. Estimated glomerular filtration rate (eGFR) was calculated. NGAL, NAG, L-FABP, and creatinine (Cr) were measured in the urine samples. The ratios of kidney injury markers to urinary Cr were used for comparisons. RESULTS: There were no significant differences in eGFR and serum chemistry values between the FS and the control group (p > 0.05). Hypoxia was detected in 67.9% of the FS patients. The FS group had significantly higher urinary kidney injury molecules to Cr ratios compared to the controls, including NGAL/Cr (17.9 ± 9.8; 6.7 ± 4.0, respectively; p < 0.001), NAG/Cr (0.55 ± 0.29; 0.21 ± 0.16, p < 0.001), and L-FABP/Cr (4.85 ± 2.93; 1.74 ± 1.16, p < 0.001). CONCLUSION: Increased urinary NGAL/Cr, NAG/Cr, and L-FABP/Cr values, in patients with FS compared to healthy controls, suggest a possible subclinical renal damage in these patients.

Tubular and glomerular kidney effects in the Chinese general population with low environmental cadmium exposure.

Cadmium (Cd), a well-known nephrotoxic agent, has received a great deal of attention from the Chinese public because of reports of its presence in rice. But very few studies have assessed the renal risk of Cd exposure in children. In this cross-sectional study, we aimed to determine whether biologic measures of Cd exposure were associated with biomarkers of early kidney damage in children, adolescents and adults. A total of 1235 subjects (2-86.8 years old) participated in this study and provided samples of blood and urine. As a result, the median urinary Cd level was 0.38 µg g(-1) creatinine in adult men and 0.42 µg g(-1) creatinine in adult women, similar to reference values observed in the United States (median: 0.32-0.40 µg L(-1) in adults). Multiple linear regressions showed Cd in urine to be significantly positively associated with effects on renal tubule biomarkers (as indicated by increased levels of N-acetyl-ß-D-glucosaminidase and ß2-microglobulin) after adjusting for age, body mass index, blood lead, and urinary density, in all age groups including children. We also found positive associations between blood Cd and renal tubule biomarkers in children. In conclusion, adverse tubular renal effects might have occurred at the current low Cd levels in the study population, including children. These findings are particularly relevant assessing health risks associated with low environmental exposures to Cd.

Thrombin-induced lysosomal exocytosis in human platelets is dependent on secondary activation by ADP and regulated by endothelial-derived substances.

Exocytosis of lysosomal contents from platelets has been speculated to participate in clearance of thrombi and vessel wall remodelling. The mechanisms that regulate lysosomal exocytosis in platelets are, however, still unclear. The aim of this study was to identify the pathways underlying platelet lysosomal secretion and elucidate how this process is controlled by platelet inhibitors. We found that high concentrations of thrombin induced partial lysosomal exocytosis as assessed by analysis of the activity of released N-acetyl-ß-glucosaminidase (NAG) and by identifying the fraction of platelets exposing the lysosomal-associated membrane protein (LAMP)-1 on the cell surface by flow cytometry. Stimulation of thrombin receptors PAR1 or PAR4 with specific peptides was equally effective in inducing LAMP-1 surface expression. Notably, lysosomal exocytosis in response to thrombin was significantly reduced if the secondary activation by ADP was inhibited by the P2Y12 antagonist cangrelor, while inhibition of thromboxane A2 formation by treatment with acetylsalicylic acid was of minor importance in this regard. Moreover, the NO-releasing drug S-nitroso-N-acetyl penicillamine (SNAP) or the cyclic AMP-elevating eicosanoid prostaglandin I2 (PGI2) significantly suppressed lysosomal exocytosis. We conclude that platelet inhibitors that mimic functional endothelium such as PGI2 or NO efficiently counteract lysosomal exocytosis. Furthermore, we suggest that secondary release of ADP and concomitant signaling via PAR1/4- and P2Y12 receptors is important for efficient platelet lysosomal exocytosis by thrombin.

Urinary, Plasma, and Serum Biomarkers' Utility for Predicting Acute Kidney Injury Associated With Cardiac Surgery in Adults: A Meta-analysis.

BACKGROUND: Early accurate detection of acute kidney injury (AKI) occurring after cardiac surgery may improve morbidity and mortality. Although several novel biomarkers have been developed for the early detection of AKI, their clinical utility in the critical intraoperative and immediate postoperative period remains unclear. STUDY DESIGN: Systematic review and meta-analysis. SETTING & POPULATION: Adult patients having cardiac surgery. SELECTION CRITERIA FOR STUDIES: EMBASE, CINAHL, Cochrane Library, Scopus, and PubMed from January 1990 until January 2015 were systematically searched for cohort studies reporting the utility of novel biomarkers for the early diagnosis of AKI after adult cardiac surgery. Reviewers extracted data for study design, population, timing of biomarker measurement and AKI occurrence, biomarker performance (area under the receiver operating characteristic curve [AUROC]), and risk of bias. INDEX TESTS: Novel urine, plasma, and serum AKI biomarkers, measured intraoperatively and in the early postoperative period (<24 hours). REFERENCE TESTS: AKI was defined according to the RIFLE, AKIN, or 2012 KDIGO criteria. RESULTS: We found 28 studies reporting intraoperative and/or early postoperative measurement of urine (n=23 studies) or plasma or serum (n=12 studies) biomarkers. Only 4 of these studies measured biomarkers intraoperatively. Overall, intraoperative discrimination by the urine biomarkers neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury marker 1 (KIM-1) demonstrated AUROCs<0.70, whereas N-acetyl-ß-d-glucosaminidase (NAG) and cystatin C had AUROCs<0.75. In the immediate 24-hour postoperative period, the urine biomarkers NGAL (16 studies), KIM-1 (6 studies), and liver-type fatty acid binding protein (6 studies) exhibited composite AUROCs of 0.69 to 0.72. The composite AUROCs for postoperative urine cystatin C, NAG, and interleukin 18 were ≤0.70. Similarly, the composite AUROCs for postoperative plasma NGAL (6 studies) and cystatin-C (5 studies) were <0.70. LIMITATIONS: Heterogeneous AKI definitions. CONCLUSIONS: In adults, known urinary, plasma, and serum biomarkers of AKI possess modest discrimination at best when measured within 24 hours of cardiac surgery.

Ambient Melamine Exposure and Urinary Biomarkers of Early Renal Injury.

Information about environmental exposure to melamine and renal injury in adults is lacking. We investigated this relationship in 44 workers at two melamine tableware manufacturing factories in Taiwan (16 manufacturers, eight grinders, ten packers, and ten administrators) and 105 nonexposed workers (controls) at one shipbuilding company who were enrolled in August-December of 2012. For melamine workers, personal and area air samples were obtained at the worksite over 1 workweek (Monday-Friday). In the same week, pre- and post-shift one-spot urine samples were collected each workday and one first-spot urine sample was collected on each weekend morning and the following Monday morning. For each control, a one-spot urine sample was collected on Friday morning. A blood sample was also obtained from each participant at this time. Melamine levels were measured in air, urine, and serum, and early renal injury biomarkers were measured in urine. Urinary melamine concentrations in manufacturers increased sharply between pre- and post-shift measurements on Monday, remained significantly elevated throughout the workweek, and decreased over the weekend; changes in urinary melamine concentrations were substantially lower for other melamine workers. Manufacturers were exposed to the highest concentrations of ambient melamine and had significantly higher urinary and serum melamine concentrations than did the controls (P<0.001). Urinary melamine levels were positively associated with urinary N-acetyl ß-d-glucosaminidase (NAG) levels but not microalbumin levels, and the detectable ß2-microglobulin rate increased in the manufacturers group. In conclusion, ambient melamine exposure may increase the levels of urinary biomarkers of renal tubular injury in this occupational setting.

Ameliorative effect of chrysin on adenine-induced chronic kidney disease in rats.

Chrysin (5, 7- dihydroxyflavone) is a flavonoid with several pharmacological properties that include antioxidant, anti-inflammatory and antiapoptotic activities. in this work, we investigated some effects of three graded oral doses of chrysin (10, 50 and 250 mg/kg) on kidney structure and function in rats with experimental chronic renal disease (CKD) induced by adenine (0.25% w/w in feed for 35 days), which is known to involve inflammation and oxidative stress. Using several indices in plasma, urine and kidney homogenates, adenine was found to impair kidney function as it lowered creatinine clearance and increased plasma concentrations of creatinine, urea, neutrophil gelatinase-associated lipocalin and N-Acetyl-beta-D-glucosaminidase activity. Furthermore, it raised plasma concentrations of the uremic toxin indoxyl sulfate, some inflammatory cytokines and urinary albumin concentration. Renal morphology was severely damaged and histopathological markers of inflammation and fibrosis were especially increased. In renal homogenates, antioxidant indices, including superoxide dismutase and catalase activities, total antioxidant capacity and reduced glutathione were all adversely affected. Most of these adenine - induced actions were moderately and dose -dependently mitigated by chrysin, especially at the highest dose. Chrysin did not cause any overt adverse effect on the treated rats. The results suggest that different doses of chrysin produce variable salutary effects against adenine-induced CKD in rats, and that, pending further pharmacological and toxicological studies, its usability as a possible ameliorative agent in human CKD should be considered.

Renal, gastrointestinal, and hemostatic effects of oral administration of meloxicam to Hispaniolan Amazon parrots (Amazona ventralis).

OBJECTIVE: To investigate renal, gastrointestinal, and hemostatic effects associated with oral administration of multiple doses of meloxicam to healthy Hispaniolan Amazon parrots (Amazona ventralis). ANIMALS: 12 Hispaniolan Amazon parrots. PROCEDURES: Birds were assigned to receive meloxicam oral suspension (1.6 mg/kg, PO, q 12 h) and 2.5 mL of tap water inserted into the crop by use of a gavage tube (n = 8) or the equivalent volume of tap water only (control group; 4) for 15 days. Urine and feces were collected 2 hours after treatment administration each day. Feces were evaluated for occult blood. Results of a CBC and serum biochemical analysis and measured N-acetyl-ß-d-glucosaminidase (NAG) activity and whole blood clotting time were evaluated before, during, and after completion of treatments. Results of urinalysis and measured urine NAG activity were also evaluated. RESULTS: Birds treated with meloxicam had a significant increase in number of WBCs and decrease in PCV from before to after treatment. The PCV also decreased significantly, compared with results for the control group; however, WBC count and PCV for all birds remained within reference ranges throughout the study. One parrot treated with meloxicam had a single high value for urine NAG activity. CONCLUSIONS AND CLINICAL RELEVANCE: Meloxicam administered orally at the dosage used in this study caused no apparent negative changes in several renal, gastrointestinal, or hemostatic variables in healthy Hispaniolan Amazon parrots. Additional studies to evaluate adverse effects of NSAIDs in birds will be needed.

Novel Biomarkers of Acute Kidney Injury After Contrast Coronary Angiography.

Acute kidney injury (AKI), defined as a rise in serum creatinine of greater than 25% from baseline measured at 48 hours after renal insult, may follow iodinated contrast coronary angiography. Termed contrast-induced nephropathy, it can result in considerable morbidity and mortality. Measurement of serum creatinine as a functional biomarker of glomerular filtration rate is widely used for detection of AKI, but it lacks sensitivity for the early diagnosis of AKI (typically rising 24 hours after functional loss) and, as a solely functional marker of glomerular filtration rate, is unable to differentiate among the various causes of AKI. These intrinsic limitations to creatinine measurement and the recognition that improved clinical outcomes are linked to a more timely diagnosis of AKI, has led investigators to search for novel biomarkers of "early" kidney injury. Several studies have investigated the utility of renal injury biomarkers in a variety of clinical settings including angiography/percutaneous coronary intervention, coronary artery bypass graft surgery, sepsis in intensive care patients, and pediatric cardiac surgery. In this article, we discuss the use of iodinated contrast for coronary procedures and the risk factors for contrast-induced nephropathy, followed by a review the potential diagnostic utility of several novel biomarkers of early AKI in the clinical settings of coronary angiography/percutaneous coronary intervention. In particular, we discuss neutrophil gelatinase associated lipocalin in depth. If validated, such biomarkers would facilitate earlier AKI diagnosis and improve clinical outcomes.

[URINE UNDER CHRONIC DYSFUNCTION OF RENAL ALLO-TRANSPLANT].

The study was organized to provide additional characteristic of chronic dysfunction of renal allo-transplant using such biomarkers of serum and urine as enzymes (alanine aminotransferase), aspartate aminotransferase, gamma- glutamiltransferase, alkaline phosphatase, N-acetyl-ß-D-glucosaminidase, interleukins (IL-2, IL-8, IL-10), beta-2- microglobulin. The chronic dysfunction of renal allo-transplant is characterized by increasing of concentration of IL-10 and beta-2-microglobulin in serum and increasing of concentration of beta-2-microglobulin, IL-2, IL-8 in urine and increasing of activity of N-acetyl-ß-D-glucosaminidase, alkaline phosphatase, aspartate aminotransferase, gamma-glutamiltransferase as compared with patients with satisfactory function of renal allo-transplant. The multivariant logistic regression analysis established that only activity of N-acetyl-ß-D-glucosaminidase in urine was reliably independently related to chronic dysfunction of renal allo-transplant. It is assumed that increasing of concentration of beta-2-microglobulin in serum testifies glomerular dysfunction and in urine--tubular dysfunction of renal allo-transplant. The enzymeuria indicates continuing damage of epithelium of proximal tubules of nephron. The classification of patients with satisfactory function and chronic dysfunction of renal allo-transplant established that the highest indicators of square under ROC-curves had concentration of beta-2-microglobulin in serum (0.858 ± 0.061) and urine (0.733 ± 0.079) and activity of N-acetyl-ß-D-glucosaminidase in urine (0.701 ± 0.061). To specify diagnosis of chronic dysfunction of renal allo-transplant the most useful (ratio of likelihood of positive result 10 and 11 correspondingly) are tests of beta-2- microglobulin in serum (more than 8.55 mkg/ml) and N-acetyl-ß-D-glucosaminidase/creatinine in urine (more than 34 nmol/(sl)/ mmol/l). These discoveries require further validation and confirmation by implementation of morphological analysis of bioptat of renal allo-transplant.