OBJECTIVETo evaluate the endocrine disrupting effects of cadmium (Cd) using OECD enhanced TG407 test guideline.

METHODSSprague-Dawley (SD) rats were randomly divided into six groups and accordingly administered with 0, 1, 2.5, 5, 10, 20 mg/kg•BW/day of Cd by gavage for 28 days. Body weight, food consumption, hematology, biochemistry, sex hormone levels, urinary β2-microglobulin, organ weights and histopathology and estrous cycle were detected.

RESULTSCd could significantly decrease animals' body weight (P<0.05). Serum luteinizing hormone (LH) at 10-20 mg/kg•BW groups and testosterone (T) at 2.5 and 10 mg/kg•BW groups decreased significantly (P<0.05). However, no statistically significant change was found in urinary &beta;2-microglobulin among Cd-treatment groups (P>0.05). Endpoints related to female reproduction including uterus weight and histopathological change at 10-20 mg/kg•BW groups showed significant increase (P<0.05). While among male rats in 2.5, 10, 20 mg/kg•BW groups, weight of prostate, thyroids, and seminal vesicle glands significantly decreased (P<0.05). Moreover, no histopathological change was observed in kidney.

CONCLUSIONResults suggested that Cd can cause endocrine disrupting effects in SD rats. Comparing with possible renal toxicity of Cd, its toxicity on endocrine system was more sensitive.

Animals ; Body Weight ; drug effects ; Cadmium ; toxicity ; Eating ; drug effects ; Endocrine Disruptors ; toxicity ; Female ; Hormones ; blood ; Kidney ; drug effects ; Male ; Organisation for Economic Co-Operation and Development ; Random Allocation ; Rats, Sprague-Dawley ; Uterus ; drug effects ; beta 2-Microglobulin ; urine

BACKGROUND/AIMS: beta2-microglobulin (beta2-MG) is freely filtered at the glomerulus and subsequently reabsorbed and catabolized by proximal renal tubular cells. Urinary beta2-MG is an early and sensitive biomarker of acute kidney injury; however, its utility as a biomarker of immunoglobulin A nephropathy (IgAN) is unclear. METHODS: We included urinary beta2-MG levels in the routine laboratory examination of all inpatients with biopsy-proven IgAN at our hospital from 2006 to 2010. We retrospectively analyzed the correlation between beta2-MG levels and clinical parameters as a prognostic biomarker of IgAN. RESULTS: A total of 51 patients (30 males, 21 females; mean age, 33.01 +/- 12.73 years) with IgAN were included in this study. Initial demographic, clinical, and laboratory data for all patients are listed. The mean initial estimated glomerular filtration rate and 24-hour urine protein levels were 94.69 +/- 34.78 mL/min/1.73 m2 and 1.28 +/- 1.75 g/day, respectively. The mean level of urinary beta2-MG was 1.92 +/- 7.38 microg/mg creatinine. There was a significant correlation between initial serum creatinine (iSCr), urine protein creatinine ratio (UPCR), and the level of beta2-MG (r = 0.744, r = 0.667, p < 0.01). There was also a significant correlation between renal function tests and the level of urinary beta2-MG (p < 0.01). Cox regression analysis showed that albumin, beta2-MG, iSCr, and UPCR were significant predictors of disease progression in IgAN. CONCLUSIONS: Urinary beta2-MG levels showed a significant correlation with renal function and proteinuria in IgAN. Thus, we propose that urinary beta2-MG may be an additional prognostic factor in patients with IgAN.
Adult ; Biological Markers/blood/urine ; Biopsy ; Creatinine/blood/urine ; Disease Progression ; Female ; Glomerular Filtration Rate ; Glomerulonephritis, IGA/blood/diagnosis/physiopathology/*urine ; Humans ; Inpatients ; Linear Models ; Male ; Middle Aged ; Multivariate Analysis ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models ; Proteinuria/blood/diagnosis/physiopathology/*urine ; Risk Factors ; Young Adult ; beta 2-Microglobulin/*urine

OBJECTIVETo analyze the clinical features of mild chronic cadmium poisoning induced by different causes.

METHODSA total of 90 patients with mild chronic cadmium poisoning, who were hospitalized in our center from 2008 to 2011 and had complete clinical data, were divided into two groups according to the causes of poisoning: environmental pollution group (n = 45) and occupational poisoning group (n = 45). The clinical symptoms, signs, laboratory indices, and treatment outcomes of all patients were analyzed.

RESULTSCompared with the environmental pollution group, the occupational poisoning group had more bone pain, less bone injury (based on imaging findings), and significantly increased abnormal rate of urinary retinol-binding protein (RBP) (P < 0.05); there were no significant differences in urinary &beta;-2 microglobulin (MG) and urinary microalbumin between the two groups (P > 0.05). Urinary cadmium, urinary RBP, and urinary &beta;-2 MG had no linear correlation between each other in the two groups. Both groups showed significant changes in urinary cadmium levels after treatment (P < 0.05).

CONCLUSIONThe clinical features of mild chronic cadmium poisoning induced by various causes are different, and active nutritional support therapy plays a positive role in improving prognosis.

Cadmium ; urine ; Cadmium Poisoning ; therapy ; urine ; Environmental Exposure ; Environmental Pollutants ; urine ; Humans ; Nutritional Support ; Occupational Exposure ; Retinol-Binding Proteins ; urine ; beta 2-Microglobulin ; urine

Renal damage is one of the most common complications and cause of death in patients with multiple myeloma (MM). The studies have pointed out that early renal impairment is risk factor for progress of this disease, timely diagnosis and prompt intervention therapy are very important to improve the prognosis and survival of MM patients. Therefore, the diagnosis of early renal damage is crucial for clinical treatment. The progress on detection of early renal damage parameters and their value are reviewed in this article.
Alpha-Globulins ; urine ; Humans ; Kidney ; physiopathology ; Multiple Myeloma ; diagnosis ; physiopathology ; Proteinuria ; Retinol-Binding Proteins ; urine ; beta 2-Microglobulin ; urine

OBJECTIVETo investigate the urinary neutrophil gelatinase-associated lipocalin (NGAL) concentration in children with idiopathic nephrotic syndrome (INS) and its clinical significance.

METHODSThirty-four children newly diagnosed with INS received oral prednisone for 4 weeks. Patients whose urinary protein did not become negative were classified as steroid-resistant nephrotic syndrome (SRNS) group, while those whose urinary protein did become negative were classified as steroid-sensitive nephrotic syndrome (SSNS) group. Morning midstream urine specimens were collected from all patients before use of prednisone and after 1, 2, 3, and 4 weeks of treatment with prednisone. Enzyme-linked immunosorbent assay was used to measure the urinary NGAL concentration. Meanwhile, urinary creatinine (Cr) concentration was measured, and urinary NGAL concentration in a single urine collection was adjusted according to the urinary Cr excretion. The two groups were compared in terms of urinary NGAL/Cr ratio.

RESULTSCompared with the SRNS group, the SSNS group had significantly decreased urinary NGAL/Cr ratios after 3 and 4 weeks of prednisone treatment (P < 0.05). Compared with the SRNS group, the SSNS group had a significantly decreased urinary &beta;2-MG/Cr ratio after 4 weeks of prednisone treatment (P < 0.05). In both groups, urinary NGAL/Cr ratio was positively correlated with urinary protein/Cr ratio (r = 0.510, P < 0.01). The results of ROC curve analysis showed when diagnostic cut-off point of urinary NGAL/Cr was 0.043 by 3 weeks after treatment, sensitivity and specificity achieved 100% and 79.2% respectively.

CONCLUSIONSUrinary NGAL/Cr ratio remains high in children with SRNS, while this ratio decreases gradually during prednisone treatment in children with SSNS, and it falls ahead of urinary &beta;2-MG/Cr ratio. These results suggest that dynamic monitoring of urinary NGAL/Cr ratio is useful for early judgment of response to prednisone in patients with INS.

Acute-Phase Proteins ; urine ; Child ; Child, Preschool ; Creatinine ; urine ; Female ; Humans ; Lipocalin-2 ; Lipocalins ; urine ; Male ; Nephrotic Syndrome ; drug therapy ; urine ; Prednisone ; therapeutic use ; Proto-Oncogene Proteins ; urine ; beta 2-Microglobulin ; urine

OBJECTIVETo study the effects of Zhuhong ointment on accumulation in the body of mercury and the pathological morphology changes of kidney, via the measurement of related indicators of the skin-impaired model rat.

METHODEighty-eight SD rats were randomly divided into the impairment control group, and high-, middle-, low-dose Zhuhong ointment groups. Each group was treated by corresponding methods for 4 weeks, and recovering for 4 weeks. Urinary potein (PRO), pH, Beta N-acetyl aminoglycosidase enzymes (NAG) and beta2-microglobulin (beta2-MG) contents in urine were taken as monitoring indexes, blood urea nitrogen (BUN) and serum creatinine (SCr) in blood and the levels of mercury in urine, blood and kidney were tested, and the pathological morphology changes of kidney were observed.

RESULTAfter treatment for 4 weeks, compared with impairment control group, the levels of mercury in urine, blood and kidney in every dose group increased significantly (P < 0.01). And the relation exists between toxicity and dose on Zhuhong ointment. After recovery for 4 weeks, the levels of mercury in urine and blood in every dose group restore normal, while the level of mercury in kidney in high- dose group still increased (P < 0.01). The level of NAG increased only in high-dose group. There was no significant difference in NAG contents between Zhuhong ointment groups and the impairment control group (P < 0.05).

CONCLUSIONExcess using Zhuhong ointment repeatedly may lead to accumulation of mercury and pathological morphology changes of kidney. So the levels of mercury in the body and related indicators of renal functions should be tested in clinical when long-term using Zhuhong ointment.

Acetylglucosaminidase ; drug effects ; urine ; Animals ; Blood Urea Nitrogen ; Creatinine ; blood ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; toxicity ; Female ; Hydrogen-Ion Concentration ; drug effects ; Kidney ; drug effects ; enzymology ; metabolism ; pathology ; Male ; Mercury ; blood ; metabolism ; urine ; Ointments ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Retinol-Binding Proteins ; drug effects ; urine ; Skin ; drug effects ; injuries ; Time Factors ; beta 2-Microglobulin ; urine

OBJECTIVETo observe the effect of long-term external use of Goupi Gao on renal function and lead accumulation in rats.

METHODRats were externally administered with Goupi Gao at different doses (7, 3.5 and 1.75 g x kg(-1)) for 90 d. At 45 days and 90 days after administration, the renal indicator, levels of blood urea nitrogen (BU) and creatinine (Cr) in serum, beta2-microglobulin (beta2-MG) and N-acetyl-beta-D-glucosaminidase (NAG) in urine were determined. Lead content in kidneys was detected by atomic absorption spectrometry.

RESULTA 90-day administration with Goupi Gao significantly enhanced the renal indicator, levels of NAG in urine and lead content in renal, when compared with the normal rats. However, the levels of BUN and beta2-MG as well as renal pathology in Goupi Gao treated rats were not obviously changed.

CONCLUSIONConsecutive administration of Goupi Gao for 90 days can increase the renal indicator and levels of NAG in urine, enhance the accumulation of lead in renal, but with no effect on excretory function of kidneys and organic changes.

Acetylglucosaminidase ; urine ; Animals ; Blood Urea Nitrogen ; Creatinine ; blood ; Drugs, Chinese Herbal ; administration & dosage ; toxicity ; Female ; Kidney ; drug effects ; metabolism ; pathology ; Lead ; analysis ; metabolism ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spectrophotometry, Atomic ; beta 2-Microglobulin ; urine

OBJECTIVETo compare the sensitivity of early renal injury induced by mercury-containing medicine in rats, including urinary N-acetyl-beta-D-glucosdminidase (NAG), beta2-microglobulin (beta2-MG), retinol binding protein (RBP) and clusterin (CLU).

METHODBadu Shengji San(BDSJS), a mercury-containing preparation of traditional Chinese medicine, was adopted as the mercury contact drug. The lowest effective toxic dose was used to observe its effect on serum creatinine (SCr), blood urea nitrogen (BUN), and such early renal injury indicators as NAG, RBP, beta2-MG and CLU and compare the sensitivity of tested indicators.

RESULTCompared to the broken skin group, groups with administration of 60 and 120 mg x kg(-1) doses of BDSJS showed no obvious difference in SCr and BUN when kidney indicators is remarkably increased and obvious pathological changes were found in kidney tubules but with significant increase in the urinary level of CLU and the levels of NAG and RBP. H&E staining of renal tubule showed that exposure of 30 mg x kg(-1) BDSJS had no significant morphological changes, but at the same concentrations, the level of RBP was markedly increased. Urinary beta2-MG levels were markedly decreased in BDSJS 30, 60 mg x kg(-1) group rats, whereas 120 mg x kg(-1) dose group showed no obvious change in urinary beta2-MG levels.

CONCLUSIONUrinary RBP, NAG and CLU were more sensitive than SCr and BUN as indicators for early renal injury in the order of RBP > NAG > CLU, and urinary RBP, NAG would increase earlier than beta2-MG.

Acetylglucosaminidase ; urine ; Animals ; Blood Urea Nitrogen ; Clusterin ; urine ; Creatinine ; blood ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; toxicity ; Epithelial Cells ; drug effects ; metabolism ; pathology ; Kidney Tubules ; drug effects ; metabolism ; pathology ; Male ; Mercury ; blood ; metabolism ; toxicity ; urine ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Retinol-Binding Proteins ; urine ; Skin ; drug effects ; injuries ; Time Factors ; beta 2-Microglobulin ; urine

OBJECTIVETo study the mercury accumulation in injured skin rats induced by Badu Shengji San (BDSJS), a traditional Chinese medicine preparation for external use.

METHODInjured skin rats were treated with BDSJS for consecutively 4 weeks. During the 4 weeks and the following 4 weeks after the drug withdrawal, samples were collected for determining mercury contents in blood, urine and kidney, with urinary N-acetyl-beta-D-glucosaminidase(NAG) and beta2-microglobulin (beta2-MG) as indicators of renal toxicity and serum biochemical indicators of hepatic and renal functions. Additionally, activated partial thromboplastin time (APTT), prothrombin time (PT) and kidney and renal pathological changes were also observed.

RESULTCompared to injured skin rats, mercury contents of blood, urine and kidney were increased significantly in low, middle and high-dose BDSJS groups administered for consecutive 4 weeks. The levels of mercury showed decreases in urine (89%, 78%, 93%) and kidney (55%, 51%, 57%), and blood mercury concentration recovered to the normal range in low, middle and high-dose BDSJS groups after the drug withdrawal for 4 weeks. Kidney coefficient and beta2-MG were remarkably increased and renal tubular epithelial cell swelling could be found in the high-dose group, and kidney coefficient, beta2-MG and renal morphology basically recovered to the normal levels after the drug withdrawal for 4 weeks.

CONCLUSIONThe administration of BDSJS for consecutively 4 weeks can cause mercury accumulation in blood and mainly in kidney. Once the accumulated mercury concentration of kidney reaches a certain level, renal tubular epithelial cells would be injured. 1.1 mg x cm(-2) of BDSJS is proved to be safe and 2.2 mg x cm(-2) can cause mild but reversible injury in the function of kidney which can be recovered after drug withdrawal for 4 weeks.

Acetylglucosaminidase ; urine ; Animals ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; toxicity ; Epithelial Cells ; drug effects ; metabolism ; pathology ; Female ; Kidney Tubules ; drug effects ; metabolism ; pathology ; Male ; Mercury ; blood ; metabolism ; toxicity ; urine ; Rats ; Rats, Sprague-Dawley ; Skin ; drug effects ; injuries ; Time Factors ; beta 2-Microglobulin ; urine

OBJECTIVE: To study correlation between urinary retinol binding protein (RBP) content and renal tubular damage. METHODS: A total of 1 353 healthy people and 186 patients with renal tubular damage diagnosed by renal biopsy were enrolled. The indicators such as endogenous creatinine clearance rate (Ccr), creatinine(Cr), urinary retinol binding protein(RBP), urinary β(2)-microglobulin(β(2)-MG), urinary N-acety1-beta-D-glucosaminidase (NAG), urine specific gravity(SG), urine osmolality of the 2 groups were examined and compared. Score of tubulointerstitial impairing and all indicators were analyzed by Spearman rank correlation analysis, and the sensitivity and specificity of indicators were calculated. RESULTS: Renal tubular damage was positively correlated with urinary RBP, β2-MG, NAG (r=0.863, P<0.001; r=0.777, P<0.001; r=0.374, P=0.002, respectively), while negatively correlated with urine osmolaling, SG (r=-0.519, P<0.001; r=-0.624, P<0.001, respectively). The specificity and sensitivity for renal tubular damage of RBP were 91.03% and 72.06%. CONCLUSION RBP is an idea marker for renal tubular damage, and is useful to diagnose renal tubular damage and assess the extent of the damage.
Acetylglucosaminidase ; urine ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers ; urine ; Case-Control Studies ; Creatinine ; urine ; Female ; Humans ; Kidney Diseases ; pathology ; Kidney Tubules ; pathology ; Male ; Middle Aged ; Retinol-Binding Proteins, Cellular ; urine ; Young Adult ; beta 2-Microglobulin ; urine