Search

Alkaline phosphatase (ALP) is a universal and important hydrolase that has been proved to be associated with several diseases. Herein, a simple and effective method was proposed for ALP detection based on the inner filter effect of p-nitrophenol (pNP) on the fluorescence of CdTe/CdS quantum dots (QDs). For the preparation of CdTe/CdS QDs, Na 2 TeO 3 was used as the Te source, and dithiol as the S source and surface ligand. The as-prepared CdTe/CdS QDs show good fluorescence properties, such as high quantum yield (∼80%), and good chemical/photo-stability. pNP is a hydrolysate of p-nitrophenol phosphate disodium salt under the catalysis of ALP, which could effectively quench the fluorescence of QDs due to the absorption spectra of pNP overlaps well with the excitation spectra of the CdTe/CdS QDs. Therefore, the prepared CdTe/CdS QDs could be applied for ALP detection. A good linear relationship ranging from 2.2 to 220 U/L was obtained with the limit of detection as low as 0.34 U/L. In addition, this method was successfully applied for the assay of ALP in human serum with the satisfactory results., (Copyright © 2018 Elsevier B.V. All rights reserved.)

We investigated the influence of abatacept (ABT) on bone mineral density (BMD) and bone metabolic markers (BMMs) in patients with rheumatoid arthritis (RA) compared to other biologic disease-modifying anti-rheumatic drugs (bDMARDs). This prospective, comparative, non-randomized study (the AIRTIGHT study; UMIN000005570) investigated the effects of ABT and other bDMARDs on bone metabolism. A total of 165 RA patients were divided into ABT (n = 50) and non-ABT (n = 115). We evaluated percentage changes in BMD (%ΔBMD) at the lumbar spine and femoral neck using dual-energy X-ray absorptiometry. Urinary levels of cross-linked N-telopeptide of type I collagen (uNTx) and bone-specific alkaline phosphatase (BAP) were used as markers of bone resorption and formation, respectively. No significant differences in 1-year completion rates were seen between ABT (64%) and non-ABT (72%; p = 0.387). The %ΔBMD at the femoral neck was significantly higher in the ABT group (0.97%) than in the non-ABT group (- 2.19%; p = 0.026). Whereas, no significant difference in %ΔBMD at the lumbar spine was observed between groups (ABT, - 0.40%; Non-ABT, - 1.67%; p = 0.524). No significant differences were observed in changes to uNTx or BAP. ABT treatment was significantly associated with increased BMD at the femoral neck (odds ratio (OR) 8.84; 95% CI 1.08-72.4; p = 0.04), and baseline lumbar osteoarthritis was significantly associated with BMD at the lumbar spine (OR 2.97; 95% CI 1.23-7.13; p = 0.02). The efficacy of ABT for increasing BMD at the femoral neck was superior to that of other bDMARDs. ABT may offer good efficacy for improving BMD at the femoral neck in patients with RA.

We investigated whether the phosphate (Pi) load in the circulation causes renal damage in non-CKD women. This cross-sectional study included 1,094 non-CKD Japanese women. Fibroblast growth factor (FGF)-23 as a parameter for the Pi load, bone alkaline phosphatase (BAP) as a bone metabolic marker, and the urinary albumin-to-creatinine ratio (UACR) as an early marker for renal damage were measured. Postmenopausal women exhibited significantly higher levels of serum Pi, FGF-23, BAP, and UACR and significantly lower eGFR than premenopausal women. In postmenopausal women, a multiple regression analysis confirmed a correlation between serum BAP and log UACR. In premenopausal women, although serum FGF-23 did not correlate with log UACR, a multiple regression analysis revealed that FGF-23 correlated with log UACR. Based on the i ncrease observed in BAP and its close relationship with log UACR in postmenopausal women, the release of Pi from bone may be linked to the systemic circulation of Pi, which has the potential to induce renal and vascular damage. Therefore, serum FGF-23 may be a useful marker for renal and vascular damage in premenopausal women; however, it currently remains unclear whether FGF-23 by itself or as a surrogate marker for the Pi load induces damage in the kidney and/or vasculature.

The diagnostic utility of urinary alkaline phosphatase (uALP) and γ-glutamyl transpeptidase (uGGT) activities in naturally occurring acute kidney injury (AKI) was investigated in a heterogeneous group of dogs. The study included client-owned dogs with AKI (n = 32), chronic kidney disease (CKD, n = 13), lower urinary tract infection (LUTI, n = 15) and healthy controls (n = 24). uGGT and uALP activities were normalised to urinary creatinine (uCr) concentrations (uGGT/uCr and uALP/uCr, respectively). uALP/uCr and uGGT/uCr were positively and significantly correlated (r = 0.619, P <0.001), and differed significantly (P ≤ 0.001) among groups, as well as between AKI and LUTI or CKD groups (P < 0.05), but not between the AKI and control groups. Areas under the receiver operator characteristics (ROC) curve for uALP/uCr and uGGT/uCr as predictors of AKI were 0.75 and 0.65, respectively, with optimal cut-off points showing poor to moderate sensitivity (59% for uALP/uCr and 79% for uGGT/uCr) and specificity (59% for uALP/uCr and 75% for uGGT/uCr). Higher cut-off points, with 90% specificity, showed low sensitivity (41% for both uALP/uCr and uGGT/uCr). In conclusion, uALP/uCr is superior to uGGT/uCr as a marker of AKI, but both uGGT/uCr and uALP/uCr have unsatisfactory discriminatory power for diagnosing naturally occurring AKI in dogs and therefore cannot be recommended as sole screening tests for canine AKI. However, both may serve as ancillary, confirmatory, biomarkers for detecting AKI in dogs if appropriate cut-off points with high specificities are used., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Urinary biomarkers have been used widely in preclinical toxicity studies to detect dysfunctions and injuries of the kidney caused by drugs under development. While they have been well studied for evaluating nephrotoxicity, knowledge of sex differences in excretion levels of urinary biomarkers remains inadequate. We conducted experiments focused on effects of endogenous sex hormones on urinary biomarkers using intact and castrated male and female rats. Comparisons of the urinary biomarker excretion levels between intact male and female rats at 5, 7, 9 and 12 weeks of age revealed higher excretion levels of leucine aminopeptidase (LAP), γ-glutamyl transpeptidase (γGTP), total protein, liver-type fatty acid-binding protein (L-FABP), cystatin C (Cys-C) and β2-microglobulin (β2-MG), and lower excretion level of kidney injury molecule 1 (Kim-1), in male rats as compared to female rats. Orchidectomized male rats showed lower urinary excretion levels of alkaline phosphatase (ALP), LAP, γGTP, N-acetyl-β-D-glucosaminidase (NAG), glucose, total protein, L-FABP, Cys-C, β2-MG and neutrophil gelatinase-associated lipocalin (NGAL), and higher urinary excretion levels of clusterin (CLU) and Kim-1, than sham-operated male rats. On the other hand, no significant differences in the urinary biomarker excretion levels excluding ALP were observed between ovariectomized and sham-operated female rats. In the present study, we demonstrated the existence of sex differences in excretion levels of urinary biomarkers that are universally used in preclinical toxicity studies, and also that these differences, especially in relation to the urinary excretions of ALP, LAP, γGTP, total protein, L-FABP, Cys-C, and β2-MG, may closely relate to the endogenous testosterone.

Cinnamomum zeylanicum has strong antioxidant properties and has been presented to have nephroprotective effects. Present work was aimed to study the nephroprotective property of the plant extract through urinary enzymes excretion, to confirm its protective effects and to observe the antibacterial activities of gentamicin in combination with the plant extract. 200mg/kg/day of the plant extracts were administered alone and as co-therapy with gentamicin. Urinary lactate dehydrogenase (LDH) and Urinary alkaline phospatase (ALP) excretions were observed through reagents kits with the help of Power-Lab 300. Antibacterial activities were assessed for gentamicin alone and in combination with the extract. Present study showed that the plant extract have excess quantity of flavonoids, which may responsible for attenuating the excessive excretion of urinary LDH. However, Urinary ALP excretion was found remained same throughout the study period in all experimental groups; might be detected in acute damage. Further, the plant also proved to have no decreasing impact on the antibacterial activities of gentamicin.

Unlabelled: 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.

Background: The aim is to evaluate via meta-analysis bone metabolism and bone mineral density (BMD) in morbidly obese patients before and after bariatric surgery., Methods: We searched Medline, EMBASE, and the Cochrane Library for relevant studies published before January 2014. The following outcomes were evaluated: serum calcium, serum parathyroid hormone (PTH), serum 25-hydroxyvitamin D [25(OH)D], serum or urinary N-telopeptide (NTX), bone-specific alkaline phosphatase (BSAP), and bone mineral density (BMD)., Results: Ten studies, including 344 patients, met our inclusion criteria. Results showed a significant decrease in serum calcium (MD = -0.10, 95 %CI -0.14 to -0.07, P < 0.00001) and increase in serum PTH (MD = 12.41, 95 %CI 6.51 to 18.31, P < 0.00001) but no significant difference in serum 25(OH)D (MD = 1.35, 95 %CI -1.12 to 3.83, P = 0.28) following bariatric surgery. There were significant increases in serum or urinary NTX (MD = 18.49, 95 %CI 3.33 to 33.66, P = 0.02) and BSAP (MD = 7.47, 95 %CI 0.21 to 14.72, P = 0.04) but a significant decrease in BMD (MD = -0.08, 95 %CI -0.13 to -0.04, P < 0.00001) after bariatric surgery., Conclusion: BMD was significantly decreased, while bone turnover was elevated, and bone remodeling was accelerated following bariatric surgery. Basal bone metabolism should be evaluated preoperatively. To prevent secondary hyperparathyroidism and bone loss, calcium and vitamin D should be monitored closely and supplemented accordingly after the surgery.

The analysis of indicators of mineral metabolism in patients with degenerative dystrophic affections of joints demonstrated that under development of osteoarthrosis process the alteration of indicators of concentration of electrolytes in blood serum, urine and synovial fluid occurs. The stage II of process is characterized by maximal alterations of indicators. The indicator of relationship between concentration of phosphate-ion and index of phosphatases of blood serum turned out the significant coefficient of correlation.

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-β-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-β-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-β-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-β-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-β-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.

Objectives: To demonstrate the attendance of mineral metabolism disorders and lithogenic factors in patients' urine with osteoporotic fracture without previously known stones, Material and Methods: 67 patients with osteoporotic fractures surgically treated in trauma service are included. The area of the fracture site, fracture mechanism and the presence of osteoporosis were the factors taken into account to diagnose osteoporotic fracture. Mineral metabolism, calciuria, oxaluria, uricosuria and citraturia in 24hours urine were analyzed. The presence of abnormal calcium and phosphorus metabolism was proved comparing hypercalciuria patients with normocalciuria ones., Results: 12 men and 55 women with mean age 68.8±14.5 years old were included. Mean Body Mass Index (BMI) was 27.4±4.1kg/m2. 42% of patients showed hypercalciuria, 34% hyperoxaluria, 34% hypocitraturia and 7% hyperuricosuria. Statistically significant differences were observed only in fasting calcium/creatinine ratio (0.17 vs. 0.08; P<.0001) when comparing patients with hypercalciuria with those with normocalciuria., Conclusions: Patients with osteoporotic fractures show different lithogenic factors in urine, mainly hypercalciuria, always in fasting conditions., (Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.)

Purpose: To investigate biomarkers of acute renal injury in Wistar rats, subjected to left renal ischemia for 10 minutes, and then compare reperfusion at 24 hours, and at 5, 7, 14 and 21 days after the procedure., Methods: Eight female and male rats between 60 and 81 days old were used in the Central Animal Facility of the UFMS. Assessed biomarkers included urine protein, urea, creatinine, glucose, sodium, potassium, urine alkaline phosphatase and gamma-glutamyl transferase activities, and protein-to-creatinine ratio; and in serum: urea, creatinine, sodium and potassium, fractional excretion of sodium, potassium, urine flow and creatinine clearance., Results: Greater variance was observed in the parameters at 24 hours and at five days (p<0.05) after reperfusion. On the 21st day, these parameters approximated those obtained for the control group., Conclusions: Renal ischemia for 10 minutes was sufficient to raise urine levels of protein, glucose, fractional excretion of potassium, urea, creatinine clearance, urine activity of gamma-glutamyltransferase and alkaline phosphatase enzymes in the first 24 hours, up to five days after reperfusion, which may indicate risk of acute kidney injury, according to the RIFLE classification.

Purpose: Recurrent kidney stones are associated with bone mineral density loss, altered bone remodeling markers, hypercalciuria and increased in fasting calcium/creatinine ratio. The objective was to determine biochemical alterations in urine in patients with osteopenia/osteoporosis without calcium kidney stones compared with patients with calcium kidney stones., Methods: This is a cross-sectional study including 142 patients who were divided in two groups: Group 1 (patients with recurrent calcium kidney stones) and Group 2 (patients with osteopenia/osteoporosis in the lumbar spine or hip). Analyses of bone mineral density, calcium-phosphorous and bone metabolism and lithogenic risk factors in fasting urine samples and 24-h urine samples were performed. Statistical analysis was carried out with SPSS 17.0. A p ≤ 0.05 was considered statistically significant., Results: Patients in Group 2 presented greater loss of bone mineral density and more elevated alkaline phosphatase, iPTH, phosphorous and β-crosslaps levels, as compared to patients in Group 1. However, Group 1 presented greater urine calcium, oxalate and uric acid and a higher proportion of hypocitraturia, hypercalciuria and hyperoxaluria, as compared to Group 2. Multivariate analysis revealed that advanced age and β-crosslaps levels are risk factors for bone mineral density loss, while low urinary calcium excretion was protective against bone demineralization., Conclusion: Patients with osteopenia/osteoporosis without lithiasis present some urinary biochemical alterations. This would explain the lack of lithogenic activity, although low calcium excretion in 24-h urine samples is a protective factor against the loss of bone mineral density.

Background: Few normative data exist for routine clinical chemistry in healthy term infants, that is, during a time of rapid development. Biochemical markers are significantly affected by these physiological changes and the lack of appropriate reference intervals may impede diagnostics in infants., Objective: To define reference intervals for calcium, phosphate, creatinine, and alkaline phosphatase in infants from 1 to 12 months of age., Design and Methods: This was an unblinded secondary analysis of 132 breastfeeding infants participating in a vitamin D3 supplementation trial (400-1600IU/d) followed prospectively until 1 year of age (NCT00381914). Serial non-fasting capillary and spot urine samples were collected for the measurement of plasma calcium, phosphate, creatinine, and alkaline phosphatase; urinary calcium, phosphate and creatinine (DxC600 Beckman Coulter); and whole-blood ionized calcium (ABL 725 Radiometer). All visits were conducted at McGill University in Montréal, Canada., Results: All analytes changed significantly over time (p<0.05), but there was no effect of sex. From 1 to 12 months, values decreased for whole-blood ionized calcium; plasma calcium, phosphate, and alkaline phosphatase; and urinary calcium:creatinine. Plasma creatinine increased. For some analytes, particularly calcium and alkaline phosphatase, values were often above the 'typical' adult or older child reference limits. Smoothed centile curves (LMS method) were developed to fill existing gaps in normative data for these analytes., Conclusions: Most analytes showed a significant change from 1 to 12 months, confirming the need for age-specific reference values. These data can assist in the generation of new reference intervals for healthy term infants and ultimately improve the care of children., (Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

It has been described renal damage in rats with vascular calcification. The organic anion transporter 5 (Oat5) is only expressed in kidney, and its urinary excretion was proposed as potential early biomarker of renal injury. The aim of this study was to evaluate the Oat5 renal expression and its urinary excretion in an experimental model of vascular calcification in comparison with traditional markers of renal injury. Vascular calcification was obtained by the administration of an overdose of vitamin D₃ (300,000 IU/kg, b.w., i.m.) to male Wistar rats. Oat5 urinary abundance was evaluated by Western blotting. Traditional markers of renal injury, such as creatinine and urea plasma levels, urinary protein levels, and urinary alkaline phosphatase (AP) activity, were determined using commercial kits. Histology was assessed by hematoxylin/eosin staining. Oat5 renal expression was evaluated by Western blotting and by immunohistochemistry. An increased expression of Oat5 in renal homogenates, in apical membranes, and in its urinary excretion was observed in rats with vascular calcification. The traditional parameters used to evaluate renal function were not modified, with the exception of histology. It is possible to postulate the urinary excretion of Oat5 as a potential noninvasive biomarker of renal injury associated with vascular calcification.

The need for low-cost diagnostic devices, both for developing and industrial countries, has led to the search for inexpensive matrixes that will allow the performance of analytical assays. One approach uses paper to create multiple microfluidic channels which allow analytes in urine or blood to flow to different detection zones the device. The choice of paper arises from its low-cost and its ability to wick biological fluids by capillary forces (i.e., an external power is not required to move fluid in a device). This chapter describes the use of a common material-cotton thread-as an alternative matrix for low-cost diagnostics. Thread-based devices can be fabricated using established techniques that rely on common house-hold tools for manipulating threads (e.g., sewing machines and looms). The fabrication schemes described here could potentially be adapted for large-scale manufacturing of diagnostic devices.

Our study aims to investigate the effect of a low-dose pioglitazone regimen on bone mineral density and bone formation-resorption markers in control and diabetic rats. Wistar rats were divided into 4 groups: non-diabetic controls, control rats receiving pioglitazone (3 mg/kg), streptozocin-treated diabetic rats (50 mg/kg), diabetic rats treated with pioglitazone (3 mg/kg). The duration of the experiment was 8 weeks. Diabetes in our rats was associated with weight loss, increased urinary calcium excretion and reduced plasma osteocalcin levels. Diabetes mellitus did not affect bone mineral density. Pioglitazone administration had no impact on bone formation and resorption markers levels and did not modify bone mineral density in the four studied groups. Pioglitazone at the 3 mg/kg dose was not associated with significant skeletal complications in our experimental model.

The aim of this study was to determine if there are sex-related differences in the acute kidney injury induced by HgCl(2) since female rats express lower levels of renal Oat1 and Oat3 (transporters involved in renal uptake of mercury) as compared with males. Control males and females and Hg-treated male and female Wistar rats were employed. Animals were treated with HgCl(2) (4 mg/kg body weight (b.w.), intraperitoneal (i.p.)) 18 h before the experiments. HgCl(2) induced renal impairment both in male and female rats. However, female rats showed a lower renal impairment than male rats. The observed increase in kidney weight/body weight ratio seen in male and female rats following HgCl(2) treatment was less in the female rats. Urine volume and creatinine clearance decreased and Oat5 urinary excretion increased in both males and females, but to a lesser degree in the latter. Urinary alkaline phosphatase (AP) activity and histological parameters were modified in male but not in female rats after HgCl(2) administration. These results indicate that the lower Oat1 and Oat3 expression in the kidney of females restricts Hg uptake into renal cells protecting them from this metal toxicity. These gender differences in renal injury induced by mercury are striking and also indicate that Oat1 and Oat3 are among the main transporters responsible for HgCl(2)-induced renal injury.

Objective: This study aims to investigate the protection of procyanidins and lycopene from the renal damage induced by mercuric chloride., Methods: Rats were treated with either procyanidins or lycopene 2h before HgCl(2) subcutaneously injection, once daily treatment for 2 successive days., Results: In comparison with HgCl(2) group, markers of renal function such as blood urea nitrogen in serum and urinary protein were decreased to (18.45±11.63) mmol/L and (15.93±9.36) mmol/L, (4.54±0.78) g/(g·Cr) and (4.40±1.12) g/(g·Cr). N-acetyl-beta-D-glucosaminidase, lactate dehydrogenase, alkaline phosphatase in urine were depressed to (125.49±11.68) U/(g·Cr), (103.73±21.79) U/(g·Cr), (101.99±12.28) U/(g·Cr), and (113.19±23.74) U/(g·Cr), (71.14±21.80) U/(g·Cr), (73.64±21.51) U/(g·Cr) in procyanidins and lycopene groups. Indicators of oxidative stress, for example, Glutathion was reduced to (45.58±9.89) μmol/(g·pro) and (45.33±5.90) μmol/(g·pro), and antioxidant enzymes such as superoxide dismutase, glutathione-peroxidase were enhanced to (43.07±10.97) U/(mg·pro) and (39.94±6.04) U/(mg·pro), (83.85±18.48) U/(mg·pro), and (85.62±12.68) U/(mg·pro). Malondialdehyde was lowered to (0.95±0.12) (μmol/g·pro) and (1.03±0.12) μmol/(g·pro) in procyanidins and lycopene groups. ROS generation was decreased by 27.63% and 16.40% and apoptosis was also decreased in procyanidins and lycopene groups respectively. Pathological changes were much better as well., Conclusion: Procyanidins and Lycopene play some protective role against mercury kidney damage., (Copyright © 2011 The Editorial Board of Biomedical and Environmental Sciences. Published by Elsevier B.V. All rights reserved.)

Background: Urinary biomarkers of tubular damage can be useful for early diagnosis of diabetic nephropathy. Thus, the aim of this study was to test the diagnostic accuracy of the urinary excretion of γ-glutamyltransferase (GGT) and alkaline phosphatase (ALP) for diagnosis of diabetic nephropathy (DN)., Methods: Fasting glucose, fructosamine, serum creatinine, glomerular filtration rate (GFR), serum uric acid, serum albumin, and urinary albumin, creatinine, GGT and ALP were assessed in 74 type 2 diabetic patients without nephropathy and 38 type 2 diabetic patients with nephropathy., Results: Urinary GGT and ALP were threefold higher in type 2 diabetic patients with nephropathy. Significant correlations were observed between urinary albumin and GGT (r=0.439, P<0.001) and urinary albumin and ALP (r=0.305, P<0.01). Areas under the curve for GGT and ALP were 0.7696 (P<0.001) and 0.7233 (P<0.001), respectively. At a cut-off value of 72U/g creatinine, GGT demonstrated a sensitivity of 96.0% and a specificity of 52.6%. At a cut-off value of 20U/g creatinine, ALP demonstrated a sensitivity and specificity of 83.8% and 36.8%, respectively., Conclusions: Urinary GGT and ALP have potential value in the diagnosis of nephropathy in type 2 diabetic patients, but GGT has a slightly higher ability to discriminate nephropathy than ALP., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Tubular enzymes (TE) are early markers of acute kidney injury (AKI), but their value for liver transplant (LT) recipients is unknown. We sought to evaluate the usefulness of TE to predict AKI after LT. We enrolled Thirty-nine adult patients without AKI who had been admitted to the Intensive Care Unit (ICU). AKI was diagnosed according to the Acute Kidney Injury Network criteria. Of these patients, 23 had received orthotopic LT and 16 controls had been admitted for other conditions. Urinary lactate dehydrogenase (LDH), alkaline phosphatase (AF) and γ-glutamyl transpeptidase (γ-GT) measured on days 1 and 3 of the ICU stay were normalized to urinary creatinine concentrations. AKI was diagnosed in 14 patients: 8 in the LT group and 6 in the control group. In the LT group, on the first day of the patients' stay in the ICU, urinary LDH (P = .032), AF (P = .022), and γ-GT (P = .002) were significantly higher among those who developed AKI; these elevations preceded those of serum creatinine. In forward receiver-operating characteristic (ROC) plot analysis, the areas under the ROC curves were 0.8, 0.86, and 0.92 for LDH, AF, and γ-GT, respectively. We concluded that TE determined early after LT are a helpful predictors of AKI., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: Micro-structural changes associated with ultra high molecular weight polyethylene particle (UHMWPE) induced osteolysis, the most frequent cause of aseptic loosening, have been intensively investigated in the mammalian calvarian model by histomorphometry and micro-computed tomography. However, little is known regarding the serological changes that occur during this process., Methods: Serological parameters for bone metabolism [calcium, phosphate, osteocalcin (OCN), deoxypyridinoline (DPD)/creatinine, alkaline phosphatase, osteoprotegerin and receptor activator of nuclear factor-κB] were analyzed in this animal model for particle induced osteolysis. Ten C57BL/6 mice were divided at random into sham operated and UHM-WPE implanted groups. Blood and urine samples were collected prior to and at 14 days after surgery., Results: Implantation of UHMWPE lead to a significant decrease in bone volume (p=0.027). Both groups (sham/UHMWPE) showed a significant increase in calcium (p=0.004/p=0.027) and phosphate (p=0.001/p=0.001), without correlation to particle implantation. Significantly higher concentrations of DPD/creatinine (p=0.034) and OCN (p=0.022) were found after implantation of UHM-WPE. In addition, parameters could not be correlated to particle induced osteolysis., Conclusions: DPD can be regarded as a valuable parameter for detecting UHMWPE induced osteolysis in the calvarian model. Further studies of serum parameters should focus on the clinical relevance in aseptic prosthetic loosening.

Bone mineral density (BMD) is affected in young adults with multiple sclerosis (MS), which leads to disabling disease. We aimed to show changes that were independent of immobilization by measuring BMD and laboratory markers of bone metabolism in mobile MS patients. We compared a total of 52 premenopausal female patients with relapsing-remitting multiple sclerosis (RRMS) to 41 women of similar age who had no risk factors for osteoporosis. The lumbar and femur BMD were measured using the dual energy X-ray absorptiometry (DXA) method. The urine concentration of serum 25-hydroxycholecalciferol (25-OH vit D(3)), and pyridinoline and deoxypyridinoline were also measured. The concentration of serum osteocalcin was measured to determine the speed of bone metabolism. The mean age of patients (+/- standard deviation [SD]) was 36.1+/-7.4. The average Expanded Disability Status Scale (EDSS) score was 2.2+/-1.8. The concentration of 25-OH vit D(3) and osteocalcin was lower, whereas the concentration of parathyroid hormone (PTH), alkaline phosphatase (ALP), pyridinoline and deoxypyridinoline was higher in the patient group. In the patient group, lumbar 2-4 BMD, T score and Z score and femur neck and trochantor BMD, T score and Z score were significantly lower than in the control group. There was a significant negative relationship between: the disease period and L 2-4 BMD, T score and Z scores; and the femoral neck BMD, T score and Z scores. There was a significant relationship between the total Functional Independence Measure score and the femoral neck, femoral trochanter BMD, T score, and Z score. There was a significant negative relationship between the average EDSS, L 2-4 and all the DXA measurements obtained from the femur. There was a significant relationship between the 25-OH vit D(3) concentration and L 2-4 T score and Z score from the DXA measurements obtained from the femur. There were no significant relationships between osteocalcin, pyridinoline, deoxypyridinoline levels and the BMD measurements. Therefore, the duration of the disease and decrease in functional capacity are the main factors that affect BMD in MS. Apart from the decrease in functional capacity, 25-OH vit D(3) deficiency and secondary PTH increase contribute to the BDM changes observed in MS., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Mercuric chloride (HgCl(2)) induces acute kidney injury (AKI) affecting glomerular hemodynamics and, more specifically, the pars recta (S3 segment) of the proximal tubule. The organic anion transporter 5 (Oat5) is exclusively localized in the apical membranes of S3 segment. Oat5 urinary excretion was recently proposed as potential early biomarker of ischemic AKI. The aim of this study was to evaluate the renal expression and the urinary excretion of the Oat5 in rats exposed to HgCl(2). Male Wistar rats were treated with a single injection of HgCl(2) at different doses of 0, 0.2, 1 and 5 mg/kg body wt (control, Hg0.2, Hg1 and Hg5 groups). The renal expression of Oat5 was evaluated by immunohistochemistry, Western blotting, and real-time PCR. Oat5 and sodium dicarboxylate cotransporter 1 (NaDC1) abundances and alkaline phosphatase activity (AP) were assayed in urine. An HgCl(2) dose-related decrease in Oat5 mRNA levels and in Oat5 protein levels in renal homogenates was observed. Hg5 rats showed an increase in urinary excretion of Oat5 and NaDC1 as well as alterations of other widely used parameters for renal dysfunction and injury (plasma creatinine, plasma urea, urinary AP activity, kidney weight, histological lesions). In Hg0.2 group only an increase of urinary excretion of Oat5 was observed. The increase of Oat5 urinary excretion in Hg1 group was associated to the beginning of tissular injury. These results suggest that urinary excretion of Oat5 might be an early indicator of mercury-induced nephropathy, which predicts the perturbation before the manifestation of histopathological damages.

Whether and when to intervene and with which therapeutic agent are key questions physicians face daily in managing patients. Biomarkers are emerging to define the course of acute kidney injury and offer an opportunity to provide targeted interventions. The EARLYARF study by Endre et al. provides a glimpse of the challenges and opportunities that lie ahead.

We performed a double-blind placebo-controlled trial to study whether early treatment with erythropoietin could prevent the development of acute kidney injury in patients in two general intensive care units. As a guide for choosing the patients for treatment we measured urinary levels of two biomarkers, the proximal tubular brush border enzymes gamma-glutamyl transpeptidase and alkaline phosphatase. Randomization to either placebo or two doses of erythropoietin was triggered by an increase in the biomarker concentration product to levels above 46.3, with a primary outcome of relative average plasma creatinine increase from baseline over 4 to 7 days. Of 529 patients, 162 were randomized within an average of 3.5 h of a positive sample. There was no difference in the incidence of erythropoietin-specific adverse events or in the primary outcome between the placebo and treatment groups. The triggering biomarker concentration product selected patients with more severe illness and at greater risk of acute kidney injury, dialysis, or death; however, the marker elevations were transient. Early intervention with high-dose erythropoietin was safe but did not alter the outcome. Although these two urine biomarkers facilitated our early intervention, their transient increase compromised effective triaging. Further, our study showed that a composite of these two biomarkers was insufficient for risk stratification in a patient population with a heterogeneous onset of injury.

Purpose: To access the effect of repeated extracorporeal shock wave (ESW) on urinary biochemical markers, Methods: 20 rats were assigned for ESW (Direx Tripter X1(R) - 14 KV) to one of two groups: G1 (n=10) one ESW; G2 (n=10) two ESWs within a 14-day interval. Within the twenty-four hour period before and after the application of shock waves, the animals were placed in metabolic cages for 24 hour urine collection. The ph, creatinine, sodium, potassium, chlorides, calcium, magnesium, phosphorus, oxalates, alkaline phosphatase and citrates were measured. Twenty-four hours after the material was collected for urinary determination, the animals underwent nephrectomy of the kidney submitted to the ESW applications and were, then, sacrificed. The kidneys were processed for histopathological examination., Results: Small variations in the biochemical markers were found in both groups, with no significant differences between the values obtained either prior to or following the ESW applications, except for citrate and alkaline phosphatase. Citraturia decreased significantly in group 2, following the second ESWL application (24.8 +/- 3.0 mg/day after the first ESWL vs. 15.3 +/- 2.2 mg/day after the second ESWL; p < 0.05). Alkaline phosphatase increased significantly following ESWL in group I (0.57 +/- 0.02 vs. 0.79 +/- 0.04 micromol/mg creatinine; p < 0.01) and also in group 2 (0.69 +/- 0.05 vs. 0.83 +/- 0.03 micromol/mg creatinine; p < 0.05). Glomerular, interstitial and sub-capsular hemorrhage with perivascular edema was found in the animals in both groups studied., Conclusions: A significant increase in urinary alkaline phosphatase was found in both groups studied, suggesting a proximal tubule lesion. In the group of rats undergoing more than one ESWL application, a smaller urinary citrate excretion was noticed, which may be a factor contributing for the formation of new calculi.

Objectives: 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., Methods: 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., Results: 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., Conclusions: 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.

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.

Objective: To investigate the effects of antioxidant therapy on the levels of mediators of shock wave induced renal injury in patients with renal calculi treated with extracorporeal shock wave lithotripsy (ESWL)., Patients and Methods: One hundred and twenty patients with renal calculi were divided into three treatment groups: Group A patients (n = 39) served as a control group; Group B patients (n = 41) were given 2 capsules of Nature Made((R)) antioxidants 2 hours before, and 2 and 8 hours after ESWL and Group C patients (n = 40) were given 2 capsules of the antioxidants at 2 and 8 hours after ESWL. Blood and urine samples were obtained from all patients just before the start of treatment with ESWL, and at 2 and 24 hours and on day 7 and 28 after ESWL. Levels of mediators of renal injury such as serum alkaline phosphatase (ALP), C-reactive protein (CRP) and lactate dehydrogenase (LDH) were measured. Urinary levels of albumin and ALP were also determined as measures of renal tubular injury., Results: Patients given antioxidants had significantly reduced mean serum concentration of ALP (p < 0.001) at 24 hours, lower serum ALP and LDH on day 7 and 28, and lowest CRP on day 28 after ESWL. They also had higher urine albumin (p < 0.001) and ALP (p < 0.001) levels (from 24 hours to day 28) compared with patients who were not given antioxidants., Conclusion: These findings suggest that oral antioxidant therapy prior to lithotripsy may reduce the severity of long term renal injury caused by the shock waves.

Study Design: A cross-sectional study., Objective: To investigate bone mineral density (BMD) and the change of bone turnover rate in postmenopausal women with lumbar spinal stenosis (LSS)., Summary of Background Data: Symptomatic LSS prevents elderly patients from performing daily activities because of back pain and neurogenic claudication. Walking intolerance due to neurologic claudication might have a negative effect on bone metabolism and BMD. However, there has been no study on the relationship between LSS and bone metabolism, especially on bone turnover rate., Methods: Sixty-seven patients were in the LSS group. As a control group, 67 age- and weight-matched subjects were selected. In both groups, BMD, bone turnover markers, vitamin D, severity of knee osteoarthritis, and demographic data were obtained. In the LSS group, walking distance without rest was also recorded. BMD, bone turnover markers, vitamin D, and severity of knee osteoarthritis were compared between the two groups. In the LSS group, the correlation between walking intolerance and bone turnover markers was also analyzed., Results: In the LSS group, urinary N-terminal telopeptide of type I collagen (u-NTx) and alkaline phosphatase were significantly elevated when compared with those of the control group (P < 0.05). However, BMD was significantly low in the control group in all of the measured sites (P < 0.05). In the LSS group, neither bone markers nor BMD were correlated with the extent of walking difficulty., Conclusion: Our study highlights the fact that limited physical activity results in high bone turnover rate in patients with LSS.

The aim of the present study was to compare a novel marker for high bone turnover with two routine markers for screening in prostate cancer patients. The markers were evaluated in two studies: (a) a cross-sectional study of 170 prostate cancer patients with local disease stratified by +/-lymph node metastases (N 0, N1) compared with controls and (b) a longitudinal study of 40 hormone refractory prostate cancer patients stratified by skeletal involvement and followed during docetaxel (+/-BM) and zoledronate (+BM) treatment. Presence or absence of bone metastases (BM) was assessed by imaging techniques (magnetic resonance imaging or X-ray) and technetium-99m scintigraphy. The serum or urinary levels of alpha C-telopeptide of collagen type I (alphaalphaCTX), prostate-specific antigen (PSA), and total alkaline phosphatase (tALP) were assessed. PSA was elevated in both N 0 and N1 patients compared with controls, whereas alphaalphaCTX was elevated only in N1 patients. tALP exhibited no difference in any of the groups. In the treatment study, PSA decreased with treatment in both the -BM and +BM groups compared with baseline values, showing similar effect of docetaxel or docetaxel/zoledronate treatment on this marker. On the contrary, alphaalphaCTX and tALP did not decrease with docetaxel treatment in the -BM group compared with baseline, whereas it decreased significantly with docetaxel/zoledronate treatment in the +BM group, already after 1 month of treatment for alphaalphaCTX. Results suggest that alphaalphaCTX is superior to PSA and tALP for identifying patients having a high risk of metastatic disease and for monitoring skeletal progression in +BM prostate cancer patients during treatment.

The effects of bicarbonate and its combination with the chelating agents, deferiprone (L1), 4,6-dimethyl-1-hydroxypyrimidin-2(1H)-one (AK-4), catechol-3,6-bis(methyleneimino-diacetic-acid) (CBMIDA), and ethane-1-hydroxy-1,1-bisphoshonate (EHBP) in removing depleted uranium (DU) for radiation emergency medicine were examined. After the intramuscular injection of DU in rats, various time schedules of bicarbonate and chelating agent administration were tested. The results indicate that the bicarbonate helps increase significantly the effects of LI and AK-4, while there were no effects of using bicarbonate alone. The effects of bicarbonate on CBMIDA were unclear, and the effects of EHBP were negative. Further studies are necessary to obtain distinctly synergic effects by the combination of chelating agents with bicarbonate.

Purpose: We evaluated the role of voided urine lysosomal enzyme N-acetyl-beta-D-glucosaminidase and brush border enzymes alkaline phosphatase and gamma-glutamyl transferase in differentiating between children with ureteropelvic junction obstruction in need of pyeloplasty and those with dilated nonobstructed kidneys suitable for conservative treatment., Materials and Methods: The study included 35 children with unilateral ureteropelvic junction obstruction treated with pyeloplasty (study group) and 15 children with dilated nonobstructed kidneys who were treated conservatively and followed for 15 months (control group). Voided urine samples were obtained before treatment from both groups, and from the study group at 1, 2, 3, 6, 9 and 12 months postoperatively and the control group at 3, 9 and 15 months of followup. N-acetyl-beta-D-glucosaminidase, alkaline phosphatase and gamma-glutamyl transferase were measured in urine samples collected from both groups., Results: In the study group the activities of preoperative urinary N-acetyl-beta-D-glucosaminidase, alkaline phosphatase and gamma-glutamyl transferase were significantly higher than in the control group. A cutoff value of 7.8 mU/mg creatinine N-acetyl-beta-D-glucosaminidase yielded a sensitivity of 97.1%, a specificity of 80% and an overall accuracy of 92%. A cutoff value of 34.5 IU/gm creatinine alkaline phosphatase resulted in a sensitivity of 91.4%, a specificity of 100% and an overall accuracy of 94%. A cutoff value of 54 IU/gm creatinine gamma-glutamyl transferase yielded a sensitivity of 62.9%, a specificity of 100% and an overall accuracy of 74%. The combination of urinary N-acetyl-beta-D-glucosaminidase and alkaline phosphatase resulted in a sensitivity of 100%, a specificity of 80% and an overall accuracy of 94%. Compared to preoperative activities, N-acetyl-beta-D-glucosaminidase, alkaline phosphatase and gamma-glutamyl transferase decreased significantly at 12 months after pyeloplasty in the study group., Conclusions: Voided urinary N-acetyl-beta-D-glucosaminidase, alkaline phosphatase and gamma-glutamyl transferase are accurate markers for differentiating between children with ureteropelvic junction obstruction requiring pyeloplasty and those with dilated nonobstructed kidneys suitable for conservative treatment. Measurement of these enzymes in voided urine could be used as a noninvasive tool for long-term followup of children with ureteropelvic junction obstruction after pyeloplasty and those receiving conservative treatment.

Background: Phase III study comparing the effect of oral ibandronate and intravenous zoledronic acid on bone markers., Patients and Methods: Breast cancer patients with bone metastases received ibandronate 50 mg/day (n = 137) or zoledronic acid 4 mg every 4 weeks (n = 138) for 12 weeks. The primary end point was mean percentage change in serum levels of cross-linked C-terminal telopeptide of type I collagen (S-CTX) at week 12. Urinary CTX (U-CTX), bone alkaline phosphatase (ALP), amino-terminal procollagen propeptide of type I collagen (PINP) and osteocalcin (OC) were also measured and bone pain and safety assessed., Results: Both bisphosphonates significantly reduced S-CTX (mean ibandronate 76% +/- 29 (SD) versus mean zoledronic acid 73% +/- 47; P < 0.001 for both versus baseline) and U-CTX (ibandronate 78% +/- 50 versus zoledronic acid 86% +/- 17; P < 0.001). The difference in S-CTX between treatments was 0.6% (confidence interval -1.7% to 3.0%), which was within the prespecified noninferiority margin. Bone ALP, PINP and OC decreased by 26%-47% compared with baseline with both bisphosphonates. Compared with zoledronic acid, ibandronate patients reported fewer adverse events overall (65.0% versus 75.9%), and on days 1-3 (8.0% versus 47.5%), including less pyrexia (overall incidence 0% versus 16.8%) and bone pain (5.8% versus 12.4%)., Conclusions: Oral ibandronate was well tolerated and statistically noninferior to zoledronic acid for percentage change in the bone resorption marker, S-CTX.

One hundred and ninety-two barrows (Duroc x Landrace x Yorkshire, initial weight 27.7 kg) were used to investigate the effects of cadmium in feed on the function of selected organs and meat colour of growing pigs. The pigs were randomly allocated into four different treatments. Each treatment included three replications with 16 pigs per replicate. The animals were fed corn-soybean basal diet and supplemented with 0, 0.5, 5.0, 10.0 mg/kg cadmium (as CdCl(2)), respectively. The feeding trial ended when the average body weight of the pigs reach 90 kg. The results showed that, compared with controls, addition of 10 mg/kg cadmium to the diet resulted in significant elevations of relative weight of liver and spleen by 18.3% (p<0.05) and 19.7% (p<0.05) respectively, and of serum glutamic-pyruvic transaminase (GPT) and glutamic-oxaloacetic transaminase (GOT) activities by 17.8% (p<0.05) and 27.4% (p<0.05) respectively; and significant decreases of Na(+)/K(+)-ATPase activity in the liver by 24.6% (p<0.05), the redness of longissimus dorsi by 26.6% (p<0.05) and 24.9% (p<0.05) at 0.75 h and 16 h post mortem, respectively, and of the myoglobin content of longissimus dorsi by 19.4% (p<0.05). No changes were found in these indices above when the pigs were fed the diet supplied with 0.5 or 5 mg/kg cadmium (p>0.05), nor in renal functions among cadmium-treatment treatments (p>0.05) as indicated is the activities of urinary N-acetyl-beta-D-glucosaminidase (NAG) and alkaline phosphatase (ALP) and the content of urinary protein. The study indicated the adverse effects of 10 mg/kg cadmium in feed on liver functions and meat colour of growing pigs.

Early data suggest that an annual i.v. infusion of zoledronic acid (ZOL) might have therapeutic use in women with osteoporosis. In this randomized, double-blind, double-dummy, multicenter, 24-week trial, we evaluated the onset of action of a single infusion of ZOL 5 mg (n=69) compared with weekly oral alendronate (ALN) 70 mg (n=59) in postmenopausal women with low bone mineral density (T score< or =-2 by DXA) as assessed by reductions in urine N-telopeptide of type I collagen (NTX) at week 1. The effects of these therapies on other markers of bone turnover, patient preference for once yearly i.v. vs. oral weekly treatment, and adverse events were also assessed. At week 1, ZOL 5 mg resulted in a significantly greater reduction in mean urine NTX from baseline than ALN 70 mg (P<0.0001). Significantly greater reduction in urine NTX and serum beta-C-telopeptide of type I collagen (beta-CTX) were also observed in the ZOL 5 mg group at all post-baseline time points. Bone-specific alkaline phosphatase (BSAP) levels showed a more gradual reduction in both the ZOL 5 mg and ALN 70 mg groups, reaching premenopausal range by week 12. A comparable proportion of patients reported adverse events in each treatment group (ZOL 5 mg, 91.3%; ALN 70 mg, 86.4%). Transient, flu-like symptoms were the most common adverse events in the ZOL 5 mg group and resulted in a higher frequency of adverse events in this group during the first 3 days of treatment. After 3 days, adverse event rates were similar in the 2 groups. The majority of patients, including those experiencing flu-like symptoms, expressed a preference for annual i.v. therapy (66.4%) compared with weekly oral therapy (19.7%). We conclude that a single i.v. infusion of ZOL 5 mg reduced urine NTX levels more rapidly than weekly oral ALN 70 mg. The majority of study patients preferred an i.v. treatment regimen of ZOL 5 mg over weekly osteoporosis therapy with ALN 70 mg.

No consensus has been reached on whether the 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, known as statins, have beneficial effects on bone health. The purpose of our study was to evaluate the effects of atorvastatin on bone metabolism by means of measuring bone turnover markers in male patients with hypercholesterolemia both at diagnosis and prospectively after 3 months of treatment. Twenty-two Japanese male patients (mean age 62.36 +/- 10.1 years) with untreated hypercholesterolaemeia were selected for this study. After 3-months treatment of atorvastatin, total cholesterol and low density lipoprotein cholesterol significantly decreased as expected (p<0.001 for both parameters). Bone-specific alkaline phosphatase (BAP) did not change significantly (p = 0.444). However, serum N-terminal telopeptide of type I collagen (NTx) significantly decreased by -19.86 +/- 26.4% (p = 0.020). In addition, delta NTx during the course of this study was negatively correlated with NTx at baseline (r = -0.645, p = 0.0008). Although there was a tendency of positive correlations of delta NTx with delta total cholesterol, delta triglycerides, and delta low density lipoprotein cholesterol, and of negative correlations of delta NTx and delta BAP with delta high density lipoprotein cholesterol, none of them reached statistical significance. Our findings suggest that atorvastatin may have potentially beneficial effects on bone metabolism in patients with hypercholesterolemia mostly by reducing bone resorption rather than by stimulating bone formation. Further studies with more patients and longer duration are warranted to evaluate its effects, if any, on prevention of osteoporosis and subsequent fractures.

Diagnosis of diabetic nephropathy in the early stages is very important since there are no clinical signs or symptoms. Urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion has been recommended as a tubular dysfunction marker that elevates before other markers, such as microalbuminuria and a decrease in creatinine clearance. In this study, we compared excretion of urinary enzymes with other markers that are used routinely in diabetic nephropathy assessment. Urinary NAG, lactate dehydrogenase (LDH), alkaline phosphatase (AP) activities, urea, creatinine, and albumin, with levels of serum glucose and creatinine and whole blood glycosylated hemoglobin (HbA1c) were measured in 32 diabetes mellitus patients and 25 healthy subjects (controls). Notably, urinary NAG, AP, LDH excretion, and microalbuminuria in the diabetic patients group were significantly increased compared to those in the control groups (P<0.001, P<0.05, P<0.01, and P<0.01, respectively). Meanwhile, our results showed that the urinary NAG excretion had the highest sensitivity and specificity (100% and 87.5%, respectively) compared to other markers. We showed that measuring urinary NAG excretion could be useful for the assessment of renal failure in diabetes mellitus patients and confirmed the use of NAG as a routine screening test.

Objective: To evaluate the distribution and elimination of pamidronate in a population of pediatric patients with renal and rheumatologic disease., Methods: Pamidronate whole blood levels were collected for the first 4 h after first exposure in 7 patients. The relationship between the rate of urinary excretion of pamidronate and bone formation or resorption was examined in 18 patients while receiving pamidronate at a total dose of 1 mg/kg/dose infused intravenously over a 4-h period. The urinary pamidronate clearances were correlated with renal function, calcium levels and measures of bone formation and resorption., Results: Pamidronate levels reached steady state concentrations of 0.9-1.5 microg/ml within 30 min and the clearance of the drug (mean+/-SE) from blood was 180.0+/-64.2 ml/kg/h with an elimination half-life of less than 1 h. The mean urinary excretion of 31.5+/-2.2% of the administered dose indicated that about 68% of the drug was incorporated into bone, confirming the uptake of pamidronate into bone was similar in pediatric patients compared to that previously reported for adults. Bone specific alkaline phosphatase, which is a marker for bone growth and formation, had significant correlation with the uptake of pamidronate into bone (p=0.002). No correlation was demonstrated with a marker for bone resorption (urinary N-telopeptide/creatinine ratio), or with creatinine clearance or calciuria when assessed 2 months after treatment., Conclusion: Pamidronate at a dose of 1 mg/kg/dose every 2 months appears safe in the short term for pediatric patients, achieves relatively low whole blood pamidronate levels, and has similar skeletal uptake of pamidronate compared to adults.

Introduction: The present study was conducted to determine whether the urinary levels of excreted enzymes, gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), aspartate (AST) and alanine aminotransferases (ALT), can efficiently indicate, within 24 h, an acute nephrotoxicity due to an overdose of paracetamol (PAR)., Methods: A baseline urine was collected from the experimental group. Thereafter, blood collected from the orbital sinus (1.0 ml) and paracetamol (650 mg/kg of body weight) was administered by gavage. After the drug administration, animals were returned to the metabolic cages and then urine was collected in the next 22 h. Blood and urine collection was performed at time 0+24 h (T(24)), as well as at times 48 and 72 h (T(48) and T(72)). After the last urine and blood collection, the rats were killed and the kidneys removed and prepared for histological examination. Plasma creatinine and urinary levels of creatinine (to determinate glomerular filtration rate-GFR), GGT, ALP, LDH, ALT and AST were measured. Kidney tissues were stained with hematoxylin and eosin stain for histological assessment., Results: Urinary levels of GGT, ALP and LDH enzymes were significantly higher (P<0.05) at T(24) when compared to the levels at T(0) and returned to basal levels at T(48) and T(72). The number of urinary epithelial cells at T(24) was significantly higher when compared to the control time (T(0)) (P<0.001). The GFR was significantly reduced 24, 48 and 72 h after the drug administration., Conclusion: The number of urinary epithelial cells and urinary enzymes levels are a simple and low cost procedure that is available and can help in the detection of renal acute lesions.

Background: Renal injury is common after open-heart surgery. Cardiopulmonary bypass contributes to the problem. We compared conventional nonpulsatile perfusion (NP) to biologically variable perfusion (BVP), which uses a computer controller to restore physiological beat-to-beat variability to roller pump flow. We hypothesized BVP would decrease renal injury after deep hypothermic circulatory arrest., Methods: Pigs were randomly assigned to either BVP (n = 9) or NP (n = 9), cooled, arrested at 18 degrees C (1 hour), reperfused, and rewarmed and maintained normothermic (3 hours). Additional pigs had NP for a similar time as above, but without circulatory arrest (n = 3), or were sham-treated without bypass (n = 3). Hemodynamics, acid-base status, temperature, and urine volumes were measured. Urinary enzyme markers of tubular injury were compared post-hoc for gamma glutamyl transpeptidase, alkaline phosphatase, and glutathione S-transferase and by urine proteomics using mass spectrometry., Results: Urine output at 1 hour after arrest was 250 +/- 129 mL with BVP versus 114 +/- 66 mL with NP (p < 0.02). All three renal enzyme markers were higher with NP after arrest compared with BVP. In animals on bypass without arrest or those sham-treated, no elevations were seen in renal enzymes. Urine proteomics revealed abnormal proteins, persisting longer with NP. Biologically variable perfusion decreased cooling to 21.0 +/- 9.0 minutes versus 31.7 +/- 7.5 minutes (p < 0.002), and decreased rewarming to 22.1 +/- 3.9 minutes versus 31.2 +/- 5.1 minutes (p < 0.002)., Conclusions: Biologically variable perfusion improved urine output, decreased enzymuria, and attenuated mass spectrometry urine protein signal with more rapid temperature changes. This strategy could potentially shorten bypass duration and may decrease renal tubular injury with deep hypothermic circulatory arrest.

Background: In experimental settings, uranium is toxic to kidneys, but effects on humans are unclear. Ingestion of water from drilled wells is a source of high uranium exposure in some populations., Methods: Uranium exposure was measured in 95 men and 98 women aged 18 to 81 years who had used drinking water from drilled wells for an average of 16 years. Urinary N-acetyl-gamma-d-glucosaminidase, alkaline phosphatase, lactate dehydrogenase, gamma-glutamyltransferase, and glutathione-S-transferase; serum cystatin C; and urinary and serum calcium, phosphate, glucose, and creatinine were measured to evaluate possible toxic effects of uranium on kidney cells and renal function. In addition, supine blood pressure was measured. Associations between uranium exposure and the outcome variables were modeled by using linear regression with adjustment for age, sex, body mass index, smoking, and analgesic use., Results: Median uranium concentration in drinking water was 25 microg/L (interquartile range, 5 to 148 microg/L; maximum, 1,500 microg/L). Indicators of cytotoxicity and kidney function did not show evidence of renal damage. No statistically significant associations with uranium in urine, water, hair, or toenails was found for 10 kidney toxicity indicators. Uranium exposure was associated with greater diastolic and systolic blood pressures, and cumulative uranium intake was associated with increased glucose excretion in urine., Conclusion: Continuous uranium intake from drinking water, even at relatively high exposures, was not found to have cytotoxic effects on kidneys in humans.

Background: Bone involvement is frequently observed in multiple myeloma (MM) patients both at diagnosis and during the course of the disease. The evaluation of biochemical markers of bone turnover could allow a dynamic evaluation of the effects of a given therapy on bone metabolism., Methods: In the present study, markers of bone resorption [urinary free pyridinoline (PYD), deoxypyridinoline (DPYD), N-terminal telopeptide of collagen I (NTX) and C-terminal telopeptide (serum crosslaps)] and of bone formation [bone alkaline phosphatase (BAP) and osteocalcin] were evaluated at diagnosis and after induction therapy in 40 patients (23M, 17F, median age = 53.5 yr) enrolled in the 'Bologna 2002' clinical trial. By study design, all patients received 4 months of combined thalidomide (100 mg/d for 2 wk then 200 mg/d), dexamethasone (40 mg/d on days 1-4, 9-12, 17-20/28 on odd cycles and on days 1-4 on even cycles) and zoledronic acid (4 mg/28 d)., Results: At diagnosis, although bone resorption markers were increased in more than 40% of the patients, only NTX (P = 0.029) and crosslaps (P = 0.000) were significantly related to the extent of skeletal lesions, as assessed by X-ray. After 4 months of therapy, a significant decrease in mean (+/-SE) urinary NTX (52.7 +/-6.9 nmol/mmol creatinine +/-6.9 vs. 14 +/- 1.42 nmol/mmol creatinine, P = 0.000) and serum crosslaps (6242.4 +/-945 pmol/L vs. 1414.9 +/- 173.8 pmol/L, P = 0.000) was observed in patients obtaining > or =partial response, at variance to what has been detected in patients showing

The reversibility of osteopenia secondary to isolated Ca deficiency (CaDef) is still not clear. We studied the effect of severe CaDef on Ca homeostasis and bone accrual in a 'hypercalcaemic' animal, the rabbit, during the post-weaning period and its reversibility on Ca supplementation. Male Belgian 5-week-old rabbit pups were fed CaDef diet (0.026 % Ca) for 10 weeks. As compared with those fed with a normal chow diet (0.45 % Ca), CaDef pups developed significant hypocalcaemia (P < 0.05), hypocalciuria (urinary Ca 76 (SEM 12) v. 17 (SEM 1) mg/l; P < 0.005), hypophosphataemia (serum inorganic P 100 (SEM 6) v. 65 (SEM 4) mg/l; P < 0.005), secondary hyperparathyroidism (SHPT) (serum intact parathyroid hormone human equivalent 18.2 (SEM 1.4) v. 125.0 (SEM 4.5) pg/ml; P < 0.001) and elevated serum calcitriol levels (34.0 (SEM 3.9) v. 91.0 (SEM 1.0) pg/ml; P < 0.005). Elevated urinary C-terminal telopeptide of class I collagen (P < 0.005) and total serum alkaline phosphatase (P < 0.005) suggested increased bone turnover. There was a significantly lower gain in bone mineral density (BMD) and bone mineral content (BMC) in the whole body and lumbar spine in vivo, and various sub-regions of the femur and tibia in vitro. Supplementation of adequate Ca (0.45 % Ca) after 15 weeks on the normal diet resulted in rapid catch-up growth, and resolution of SHPT. Rapid gain in various BMD and BMC parameters continued at 30 weeks of age, and both were comparable with those in rabbits on a normal diet. We conclude that Ca deficiency-induced SHPT and poor bone accrual in growing rabbit pups are rapidly reversible with Ca supplementation. The present study indicates that early intervention may be a more appropriate window period for human nutritional corrective measures.

Aim: This study has been carried out to see whether renal function is acutely altered in patients undergoing sevoflurane anaesthesia. For this purpose, the urinary levels of markers of renal tubular function, namely leucine amino peptidase (LAP), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and beta-2 microglobulin (beta-2M), and urinary albumin as a predictor of renal glomerular function were measured before and after sevoflurane anaesthesia., Methods: This study was comprised of 20 patients (11 males and nine females) aged 18-55, who underwent various elective surgical procedures under general anaesthesia. Urine samples of all patients were collected before and 1, 2 and 8 h after the anaesthesia. The levels of LAP, GGT, beta-2M, and albumin were then expressed as factored by urinary creatinine. In all patients, the anaesthesia was maintained with sevoflurane (2% end-tidal) at a high flow-rate (6 L/min)., Results: Urinary beta-2M and LAP levels after anaesthesia were unchanged (P > 0.05). While urinary GGT and ALP levels were found elevated in the first hour, LDH levels were higher in the second hour (P < 0.05). They returned to normal levels in the later periods after the anaesthesia. Urinary albumin excretion (UAE) was significantly elevated in the second hour after the anaesthesia (P < 0.001). Although UAE was decreased in the eighth hour after the anaesthesia, it still remained higher than the pre-anaesthesia level (P < 0.001)., Conclusions: These results suggest that a 2% end-tidal concentration of sevoflurane at a high flow-rate (6 L/min) acutely alters renal glomerular function but does not have a significant acute effect on biochemical markers of renal tubular damage.

Background: In clinical practice, the assessment and follow-up of early renal dysfunction is important in diabetic nephropathy. Therefore, this study was designed to determine whether the serum cystatin C (Cys C) and activities of some tubular enzymes could be used as screening markers for renal dysfunction in diabetic patients., Methods: Serum Cys C levels and urinary activities of N-acetyl-b-D-glucosaminidase (NAG), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) and whole blood glycolyse hemoglobin (HbA1C) were measured in 56 diabetic patients and 20 healthy subjects (controls). The results were compared with serum creatinine (Cr) and creatinine clearance (CCr), which were measured and estimated with the Cockcroft-Gault formula (CCG) and 24-hr urine microalbuminuria (MAU). We examined the influence of albuminuria, HbA1C and CCr levels of patients on the levels of the analyzed parameters. Sensitivity and specificity for the diagnosis of renal impairment were calculated by a receiver operating characteristics (ROC) curve for serum Cys C, Cr and urinary enzymes., Results: In normoalbuminurics, only serum Cys C levels and urinary NAG activities were found elevated as compared to controls. In addition to the elevation of serum Cys C levels and urinary activities of NAG, urinary ALP and LDH activities were also found elevated in microalbuminurics. Serum Cys C levels and urinary NAG, ALP, LDH activities started to increase above the normal range when CCr declined and while serum Cr was in the normal range in patients with 50

There are limited data on vitamin D insufficiency in healthy children. The aim of this study was to describe the prevalence and determinants of vitamin D insufficiency and its association with bone turnover in adolescent boys (N = 136, mean age 16 years). Sun exposure and physical activity were assessed by questionnaire. Vitamin D stores were assessed by serum 25-hydroxyvitamin D3 (25[OH]D3). Bone turnover was assessed by bone-specific alkaline phosphatase (BAP) and urinary pyridinoline (PYR) to creatinine (Cr) ratio (mmol PYR/micromol Cr). The mean 25(OH)D3 level was low (44 nmol/l; 68% < 50 nmol/l; range, 16-87) and was associated with self-reported sun exposure on winter weekends (r = 0.23, p = 0.01), school holidays (r = 0.22, p = 0.01), and weekdays (r = 0.17, p = 0.05). It was also associated with number of sports (r = 0.34, p < 0.001) and vigorous activity (r = 0.22, p = 0.01) but not television, computer, and video watching (r = -0.04, p = 0.68). In multivariate analysis, number of sports but not total sun exposure remained significantly associated with 25(OH)D3. Furthermore, 25(OH)D3 was significantly associated with BAP in cutpoint analysis (cutpoint 55 nmol/l, p = 0.03) but not continuous analysis (r = -0.12, p = 0.16) and PYR in both forms (r = -0.23, p = 0.01, cutpoint 43 nmol/l, p = 0.01). In conclusion, vitamin D insufficiency is common in healthy adolescent boys in winter in our setting, is primarily derived from sports-related sun exposure, and is associated with bone turnover markers. These data suggest that a 25(OH)D3 level of at least 43-55 nmol/l is required for optimal bone health in children.

Secreted alkaline phosphatase (SEAP) and Metridia luciferase (MLuc) are useful reporter molecules in vitro, but little is understood about their usefulness in vivo. In this study, we investigated in vivo activity of recombinant SEAP and MLuc in blood and urine. When SEAP-transfected cells or recombinant SEAP were injected into rats, substantial increase in the level of serum SEAP was observed. In contrast, activity of SEAP was not detected in urine of rats injected with either the SEAP-transfected cells or recombinant SEAP. SEAP activity was also undetectable in urine of SEAP-injected Nagase analbuminemic rats in which glomerular permeability to macromolecules is enhanced. When MLuc-transfected cells were implanted into rats, activity of MLuc was undetectable not only in urine but also in serum. Even immediately after intravenous injection of recombinant MLuc, activity of MLuc was not detected in serum. Subsequent experiments revealed that, in contrast to SEAP, MLuc was rapidly inactivated either by rat serum, fetal bovine serum, or human serum. Albumin was identified as the molecule responsible for the inhibition of MLuc activity. These data elucidated advantages and limitations of secreted reporter molecules SEAP and MLuc under in vivo situations.