Cross sectional longitudinal study of spot morning urine protein:creatinine ratio, 24 hour urine protein excretion rate,glomerular filtration rate,and end stage renal failure in chronic renal disease in patients without diabetes.

OBJECTIVE: To evaluate whether the protein:creatinine ratio in spot morning urine samples is a reliable indicator of 24 hour urinary protein excretion and predicts the rate of decline of glomerular filtration rate and progression to end stage renal failure in non-diabetic patients with chronic nephropathy. DESIGN: Cross sectional correlation between the ratio and urinary protein excretion rate. Univariate and multivariate analysis of baseline predictors, including the ratio and 24 hour urinary protein, of decline in glomerular filtration rate and end stage renal failure in the long term. SETTING: Research centre in Italy. SUBJECTS: 177 non-diabetic outpatients with chronic renal disease screened for participation in the ramipril efficacy in nephropathy study. MAIN OUTCOME MEASURES: Rate of decline in filtration rate evaluated by repeated measurements of unlabelled iohexol plasma clearance and rate of progression to renal failure. RESULTS: Protein:creatinine ratio was significantly correlated with absolute and log transformed 24 hour urinary protein values (P = 0.0001 and P < 0.0001, respectively.) Ratios also had high predictive value for rate of decline of the glomerular filtration rate (univariate P = 0.0003, multivariate P = 0.004) and end stage renal failure (P = 0.002 and P = 0.04). Baseline protein:creatinine ratios and rate of decline of the glomerular filtration rate were also significantly correlated (P < 0.0005). In the lowest third of the protein:creatinine ratio (< 1.7) there was 3% renal failure compared with 21.2% in the highest third (> 2.7) (P < 0.05). CONCLUSIONS: Protein:creatinine ratio in spot morning urine samples is a precise indicator of proteinuria and a reliable predictor of progression of disease in non-diabetic patients with chronic nephropathies and represents a simple and inexpensive procedure in establishing severity of renal disease and prognosis.     

Protein concentration in urine of normal owl monkeys.

The excretion of urinary protein was evaluated in 62 owl monkeys using timed urine collections. The ratio of urine protein to urine creatinine concentrations (Up/c) was determined for each monkey. Linear regression analysis was used to calculate the correlation between that ratio and urine protein (mg/dl) and 24-hour urinary protein loss (mg/kg). The coefficient of determination for Up/c to urine protein and 24-hour urinary protein loss was significant (P less than or equal to 0.0001). Determination of the Up/c in a urine specimen was found to be an acceptable diagnostic technique for detection and quantitative estimation of proteinuria.     

Age-dependent excretion of alanine aminopeptidase, alkaline phosphatase, gamma-glutamyltransferase and N-acetyl-beta-D-glucosaminidase in human urine

Urinary excretion of alanine aminopeptidase, alkaline phosphatase, gamma-glutamyltransferase and N-acetyl-beta-D-glucosaminidase was determined in gel-filtered samples of morning random urine specimens of 442 subjects of various ages (5 days to 58 years). Enzyme excretion related to urinary creatinine (enzyme/creatinine ratio; U/mmol creatinine) significantly decreased with increasing age. Sex-related differences of some enzyme excretions were found in age groups over 6 years. From these investigations, we calculated upper reference intervals (97.5 percentiles) for 5 age-dependent groups of children and adolescents and for one group of adults.     

Urinary zinc excretion and zinc status of patients with Β-thalassemia major

In this study, zinc status and urinary zinc excretion with and without desferrioxamine (DFO) infusion and the relationship between urinary zinc excretion and renal tubular dysfunction in thalassemia major (TM) patients were investigated. Forty TM patients were given four DFO infusions on alternate days over a 1-wk period prior to the transfusion. On each day that DFO was given, a 24-h urine collection initiated. DFO was omitted for 1-wk before the following transfusion and during the period four 24-h urine collections were performed. Twenty healthy children provided 24-h urine collection as controls. Blood samples were taken on each of two consecutive transfusion days of the patients and from the controls. Urinary zinc excretion was measured and plasma and red blood cell (RBC) zinc analysis were performed by inductively coupled plasma-atomic emission spectrophotometry. UrinaryN-acetyl-Β-D-glucosaminidase (NAG) activity and creatinine were determined in morning urine specimens. The mean plasma zinc concentration was significantly lower in the patients not given DFO compared to the values of the patients given DFO and the control group. The mean RBC zinc concentration (Μmol/g Hb) in the patients (with and without DFO) and the control group were similar. Urinary zinc excretion was significantly higher in the patients receiving DFO compared to the control group, whereas urinary zinc excretion in the patients not given DFO was not different from the controls. Urinary NAG indices (U/g Cr) were significantly higher in the patients compared to controls. Urinary zinc excretion was correlated with the urinary NAG indices.     

Diagnostic Accuracy of Urine Protein/Creatinine Ratio Is Influenced by Urine Concentration

Background

The usage of urine protein/creatinine ratio to estimate daily urine protein excretion is prevalent, but relatively little attention has been paid to the influence of urine concentration and its impact on test accuracy. We took advantage of 24-hour urine collection to examine both urine protein/creatinine ratio (UPCR) and daily urine protein excretion, with the latter as the reference standard. Specific gravity from a concomitant urinalysis of the same urine sample was used to indicate the urine concentration.

Methods

During 2010 to 2014, there were 540 adequately collected 24h urine samples with protein concentration, creatinine concentration, total volume, and a concomitant urinalysis of the same sample. Variables associated with an accurate UPCR estimation were determined by multivariate linear regression analysis. Receiver operating characteristic (ROC) curves were generated to determine the discriminant cut-off values of urine creatinine concentration for predicting an accurate UPCR estimation in either dilute or concentrated urine samples.

Results

Our findings indicated that for dilute urine, as indicated by a low urine specific gravity, UPCR is more likely to overestimate the actual daily urine protein excretion. On the contrary, UPCR of concentrated urine is more likely to result in an underestimation. By ROC curve analysis, the best cut-off value of urine creatinine concentration for predicting overestimation by UPCR of dilute urine (specific gravity ≦ 1.005) was ≦ 38.8 mg/dL, whereas the best cut-off values of urine creatinine for predicting underestimation by UPCR of thick urine were ≧ 63.6 mg/dL (specific gravity ≧ 1.015), ≧ 62.1 mg/dL (specific gravity ≧ 1.020), ≧ 61.5 mg/dL (specific gravity ≧ 1.025), respectively. We also compared distribution patterns of urine creatinine concentration of 24h urine cohort with a concurrent spot urine cohort and found that the underestimation might be more profound in single voided samples.

Conclusions

The UPCR in samples with low or high specific gravity is more likely to overestimate or underestimate actual daily urine protein amount, respectively, especially in a dilute urine sample with its creatinine below 38.8 mg/dL or a concentrated sample with its creatinine above 61.5 mg/dL. In particular, UPCR results should be interpreted with caution in cases that involve dilute urine samples because its overestimation may lead to an erroneous diagnosis of proteinuric renal disease or an incorrect staging of chronic kidney disease.     

Validity of the first morning urine collection for screening for microalbuminuria in the diabetic

With the aim of evaluating the reliability of morning urine collection, compared to the overnight period, in the assessment of microalbuminuria, we measured albumin and creatinine concentration in overnight and morning urine of 125 diabetic outpatients. The overnight albumin excretion rate resulted in relation to morning albumin concentration and morning albumin/creatinine ratio. The sensitivity of this method of urine collection, compared to the overnight sample, was 55.5%, the specificity 96.6% and the predictive value 43% using, as a measure, the albumin concentration. These values improved by correcting albumin for creatinine concentration. Concerning high risk albuminuria (overnight excretion rate greater than 30 micrograms/min), we found a sensitivity and predictive value of the first morning collection highly improved by the albumin/creatinine ratio. It is concluded that the first morning urine collection can be used in the diagnosis of microalbuminuria in diabetic patients, especially when we calculate the albumin/creatinine ratio. This simple and reliable method allows the identification of microalbuminuric subjects and of the patients at risk to develop clinical nephropathy with a good sensitivity.     

Wilm's Tumor-1 Protein Levels in Urinary Exosomes from Diabetic Patients with or without Proteinuria

Background

Podocyte injury is an early feature of diabetic nephropathy (DN). Recently, urinary exosomal Wilm''s tumor-1 protein (WT1), shed by renal epithelial cells, has been proposed as a novel biomarker for podocyte injury. However, its usefulness as biomarker for early diabetic nephropathy has not been verified yet. We investigated urinary exosomal WT1 in type-1 diabetic patients to confirm its role as a non-invasive biomarker for predicting early renal function decline.

Methods

The expression of WT1 protein in urinary exosomes from spot urine samples of type-1 diabetes mellitus patients (n = 48) and healthy controls (n = 25) were analyzed. Patients were divided based on their urinary albumin excretion, ACR (mg/g creatinine) into non- proteinuria group (ACR<30 mg/g, n = 30) and proteinuria group (ACR>30 mg/g, n = 18). Regression analysis was used to assess the association between urinary exosomal levels of WT1 with parameters for renal function. Receiver Operating Characteristic (ROC) curve analysis was used to determine the diagnostic performance of exosomal WT-1.

Results

WT1 protein was detected in 33 out of 48 diabetic patients and in only 1 healthy control. The levels of urinary exosomal WT1 protein is significantly higher (p = 0.001) in patients with proteinuria than in those without proteinuria. In addition, all the patients with proteinuria but only half of the patients without proteinuria were positive for exosomal WT1. We found that the level of exosomal WT1 were associated with a significant increase in urine protein-to-creatinine ratio, albumin-to-creatinine ratio, and serum creatinine as well as a decline in eGFR. Furthermore, patients exhibiting WT1-positive urinary exosomes had decreased renal function compared to WT1-negative patients. ROC analysis shows that WT-1 effectively predict GFR<60 ml. min-1/1.73 m².

Conclusion

The predominant presence of WT1 protein in urinary exosomes of diabetic patients and increase in its expression level with decline in renal function suggest that it could be useful as early non-invasive marker for diabetic nephropathy.     

Diagnostic accuracy of urinary spot protein:creatinine ratio for proteinuria in hypertensive pregnant women: systematic review

Objective To review the spot protein:creatinine ratio and albumin:creatinine ratio as diagnostic tests for significant proteinuria in hypertensive pregnant women.Design Systematic review.Data sources Medline and Embase, the Cochrane Library, reference lists, and experts.Review methods Literature search (1980-2007) for articles of the spot protein:creatinine ratio or albumin:creatinine ratio in hypertensive pregnancy, with 24 hour proteinuria as the comparator.Results 13 studies concerned the spot protein:creatinine ratio (1214 women with primarily gestational hypertension). Nine studies reported sensitivity and specificity for eight cut-off points, median 24 mg/mmol (range 17-57 mg/mmol; 0.15-0.50 mg/mg). Laboratory assays were not well described. Diagnostic test characteristics were recalculated for a cut-off point of 30 mg/mmol. No significant heterogeneity in cut-off points was found between studies over a range of proteinuria. Pooled values gave a sensitivity of 83.6% (95% confidence interval 77.5% to 89.7%), specificity of 76.3% (72.6% to 80.0%), positive likelihood ratio of 3.53 (2.83 to 4.49), and negative likelihood ratio of 0.21 (0.13 to 0.31) (nine studies, 1003 women). Two studies of the spot albumin:creatinine ratio (225 women) found optimal cut-off points of 2 mg/mmol for proteinuria of 0.3 g/day or more and 27 mg/mmol for albuminuria.Conclusion The spot protein:creatinine ratio is a reasonable “rule-out” test for detecting proteinuria of 0.3 g/day or more in hypertensive pregnancy. Information on use of the albumin:creatinine ratio in these women is insufficient.     

Decrease in Urinary Creatinine Excretion in Early Stage Chronic Kidney Disease

Background

Little is known about muscle mass loss in early stage chronic kidney disease (CKD). We used 24-hour urinary creatinine excretion rate to assess determinants of muscle mass and its evolution with kidney function decline. We also described the range of urinary creatinine concentration in this population.

Methods

We included 1072 men and 537 women with non-dialysis CKD stages 1 to 5, all of them with repeated measurements of glomerular filtration rate (mGFR) by ⁵¹Cr-EDTA renal clearance and several nutritional markers. In those with stage 1 to 4 at baseline, we used a mixed model to study factors associated with urinary creatinine excretion rate and its change over time.

Results

Baseline mean urinary creatinine excretion decreased from 15.3±3.1 to 12.1±3.3 mmol/24 h (0.20±0.03 to 0.15±0.04 mmol/kg/24 h) in men, with mGFR falling from ≥60 to <15 mL/min/1.73 m², and from 9.6±1.9 to 7.6±2.5 (0.16±0.03 to 0.12±0.03) in women. In addition to mGFR, an older age, diabetes, and lower levels of body mass index, proteinuria, and protein intake assessed by urinary urea were associated with lower mean urinary creatinine excretion at baseline. Mean annual decline in mGFR was 1.53±0.12 mL/min/1.73 m² per year and that of urinary creatinine excretion rate, 0.28±0.02 mmol/24 h per year. Patients with fast annual decline in mGFR of 5 mL/min/1.73 m² had a decrease in urinary creatinine excretion more than twice as big as in those with stable mGFR, independent of changes in urinary urea as well as of other determinants of low muscle mass.

Conclusions

Decrease in 24-hour urinary creatinine excretion rate may appear early in CKD patients, and is greater the more mGFR declines independent of lowering protein intake assessed by 24-hour urinary urea. Normalizing urine analytes for creatininuria may overestimate their concentration in patients with reduced kidney function and low muscle mass.     

Transferrin and albumin excretion as a measure of glomerular function

Albumin and transferrin are relatively small protein molecules and highly negatively charged. Their levels in urine are a useful indicator of the integrity of membrane barriers of the kidney glomerular capillary wall. The present data shows that the excretion rates of albumin and transferrin and their kinetics of excretions are similar. Thus, their filtration mechanisms at the active site of the kidney membrane pores are similar. Total urinary protein/creatinine or albumin or transferrin/creatinine ratio were found to be linear and highly significant. Their measurement could indicate the degree of impaired glomerular permeability. Also, in the present study, a rapid biochemical method of measurement of the selectivity of proteinuria based on the transferrin/albumin ratios in random samples is reported. This method is particularly useful in the early stages of glomerular basement membrane damage.     

Oxidative DNA damage in vivo: relationship to age, plasma antioxidants, drug metabolism, glutathione-S-transferase activity and urinary creatinine excretion

Oxidative DNA modification has been implicated in development of certain cancers and 8-oxodG, the most abundant and mutagenic DNA modification, has for some time been considered a biomarker of this activity. Urinary excretion of 8-oxodG over 24h has been used to estimate the rate of damage to DNA, and animal studies have supported this rationale. Reported determinants include tobacco smoking, heavy exercise, environmental pollution and individual oxygen consumption. Samples from three published studies were used to determine the association of urinary 8-oxodG excretion with age, plasma antioxidants, the glutathione-S-transferase phenotype and the activity of the xenobiotic metabolising enzyme CYP1A2. In the age range 35-65 years, age was not related to urinary 8-oxodG excretion, and there were no relations to either the glutathione-S-transferase phenotype or to the plasma antioxidants: vitamin C, alpha-tocopherol, beta-carotene, lycopene or coenzyme Q10. The activity of CYP1A2 showed a significant correlation in two of the three studies, as well as a significant correlation of 0.26 (p < 0.05) in the pooled data set. Regression analysis of CYP1A2 activity on 8-oxodG indicated that 33% increase in CYP1A2 activity would correspond to a doubling of 8-oxodG excretion. This finding needs to be confirmed in independent experiments. Spot morning urine samples can under certain circumstances be used to estimate 8-oxodG excretion rate provided that creatinine excretion is unchanged (in paired experiments) or comparable (in un-paired experiments), as evaluated from the correlation between 8-oxodG excretion in 24 h urine samples and in morning spot urine samples corrected for creatinine excretion (r = 0.50, p < 0.05). We conclude that 8-oxodG excretion is determined by factors like oxygen consumption and CYP1A2 activity rather than by factors like plasma antioxidant concentrations.     

Validation and Assessment of Three Methods to Estimate 24-h Urinary Sodium Excretion from Spot Urine Samples in Chinese Adults

24-h urinary sodium excretion is the gold standard for evaluating dietary sodium intake, but it is often not feasible in large epidemiological studies due to high participant burden and cost. Three methods—Kawasaki, INTERSALT, and Tanaka—have been proposed to estimate 24-h urinary sodium excretion from a spot urine sample, but these methods have not been validated in the general Chinese population. This aim of this study was to assess the validity of three methods for estimating 24-h urinary sodium excretion using spot urine samples against measured 24-h urinary sodium excretion in a Chinese sample population. Data are from a substudy of the Prospective Urban Rural Epidemiology (PURE) study that enrolled 120 participants aged 35 to 70 years and collected their morning fasting urine and 24-h urine specimens. Bias calculations (estimated values minus measured values) and Bland-Altman plots were used to assess the validity of the three estimation methods. 116 participants were included in the final analysis. Mean bias for the Kawasaki method was -740 mg/day (95% CI: -1219, 262 mg/day), and was the lowest among the three methods. Mean bias for the Tanaka method was -2305 mg/day (95% CI: -2735, 1875 mg/day). Mean bias for the INTERSALT method was -2797 mg/day (95% CI: -3245, 2349 mg/day), and was the highest of the three methods. Bland-Altman plots indicated that all three methods underestimated 24-h urinary sodium excretion. The Kawasaki, INTERSALT and Tanaka methods for estimation of 24-h urinary sodium excretion using spot urines all underestimated true 24-h urinary sodium excretion in this sample of Chinese adults. Among the three methods, the Kawasaki method was least biased, but was still relatively inaccurate. A more accurate method is needed to estimate the 24-h urinary sodium excretion from spot urine for assessment of dietary sodium intake in China.     

The renal excretion of selenium.

The excretion of selenium in urine was determined in West German healthy volunteers. Women excrete 17.7 +/- 4.2 micrograms Se/d and men 19.0 +/- 9.0 micrograms Se/d. The daily selenium excretion per gram creatinine is 13.5 +/- 3.8 micrograms Se/g crea for women and 9.8 +/- 3.3 micrograms Se/g crea for men. The clearance of selenium from the plasma is calculated with 0.18 mL/min. The selenium excretion per day is positively correlated with the 24 h excretion of urea and creatinine. The correlation of the selenium excretion with the urea excretion is most probably owing to the fact that the selenium intake of West Germans is linked primarily to foods with high protein contents. That the selenium excretion is directly correlated with the creatinine excretion is an indicator that the muscle, which accounts for nearly 50% of the whole body selenium in West German adults, influences the selenium excretion in urine. The positive correlation of the selenium excretion with the potassium excretion also indicates that the muscle mass contributes significantly to the selenium excretion in urine. Another indicator that the selenium excretion is influenced by the muscle is that after intensive muscular activity (running), selenium excretion is enhanced. The 24 h selenium excretion is dependent on the glomerular filtration rate of the kidney characterized by the creatinine clearance. This result is important, because if the selenium excretion is used as parameter for the selenium status of humans, the kidney function should be known. This is a limitation for the use of the urinary selenium excretion as parameter for the selenium status. This is especially important for patients whose glomerular filtration rate is low. The 24 h selenium excretion is further influenced by the 24 h urine volume. Selenium losses via urine may be concomitant with protein losses in urine.     

Effect of indomethacin on proteinuria in rats with autologous immune complex nephropathy

Although non-steroidal anti-inflammatory agents have been used to reduce levels of urinary protein excretion in patients with the nephrotic syndrome, the general usefulness of these drugs in proteinuric states remains unclear. The present study was designed to confirm the efficacy and to investigate some of the mechanism/s of action of non-steroidal anti-inflammatory agents in animals with proteinuria as the result of a single form experimental renal disease. Autologous immune complex nephropathy was produced in groups of Lewis rats by the administration of autologous tubular F×1A antigen. After marked proteinuria developed, indomethacin (8 mg/kg/day) was administered orally to one group of animals for five days while a control group received only vehicle. The level of urinary protein excretion in the indomethacin treated animals was 420 ± 198 mg/day compared to a level of 1180 ± 306 seen in the untreated animals (p < 0.05). When the indomethacin-treated and control animals were compared, the reduction in proteinuria could not be found to be associated with a change in the glomerular filtration rate, urine electrolyte or osmolar excretion rates, electron microscopic appearance of the glomerular basement membrane, or a change in the glomerular permeability to neutral dextran. Treatment of animals with either sodium salicylate or lower doses of indomethacin (both of which resulted also in significant falls in urinary prostaglandin E excretion rates) failed to reduce the levels of proteinuria. Thus, indomethacin was capable of reducing the levels of protein excretion in rats with autologous immune complex nephropathy although the mechanism of action of this agent remains unclear.     

食盐加碘后甲状腺摄131I 率的变化及其与尿碘的关系

目的：了解食盐加碘后健康人及甲亢患者甲状腺摄131I 率的变化及其与24 小时尿碘含量的相关性,探讨甲状腺摄131I 率与 碘营养状况的关系。方法：对比食盐加碘前后健康体检者及甲亢患者甲状腺摄131I 率的变化,分析健康体检者甲状腺摄131I 率、晨 尿碘浓度及经肌酐校正的尿碘含量与24小时尿碘含量的相关关系。结果：健康人及甲亢患者食盐加碘后3、6 及24 小时甲状腺 摄131I 率均显著降低;健康体检者甲状腺摄131I 率与24 小时尿碘含量呈负相关（r=－0.7651, P<0.001）,晨尿碘浓度与24 小时尿碘 含量呈正相关（r=0.8231, P<0.001）,经肌酐校正的尿碘含量与24 小时尿碘含量呈正相关（r=0.9054, P<0.001）。结论：食盐加碘对甲 状腺摄131I 率有显著影响,应重新确立甲状腺摄131I 率的正常范围及甲亢的诊断标准;经肌酐校正的尿碘含量较晨尿碘浓度能更 准确地反映碘营养状况;甲状腺摄131I率可作为评估个体碘营养状况的指标,可以稳定地反映近期的碘营养状况。     

Urinary fibrin-fibrinogen degradation products in nephrotic syndrome.

The urinary concentration of fibrin-fibrinogen degradation products (F.D.P.) was measured in 90 patients with proteinuria above 2 g/1 and correlated with proteinuria, differential protein clearances, serum urea and creatinine, and renal biopsy findings. There was a linear correlation (r equals 0-7; P less than 0-001) between the urinary F.D.P. excretion and the selectivity of the proteinuria such that patients with highly selective proteinuria excreted only small amounts of F.D.P. whereas those with non-selective proteinuria excreted much higher levels. There was a significant correlation between the urinary F.D.P. excretion and the urine:serum (U:S) ratio of IgG excretion but not with the U:S ratio or urinary excretion of albumin or transferrin. Sephadex G200 column chromatography of the concentrated urine in 26 cases showed that patients with highly selective proteinuria excreted predominantly F.D.P. of low molecular weight in the urine whereas those with non-selective proteinuria excreted mainly fibrinogen and products of high molecular weight. Hence the type and quantity of F.D.P. in the urine are determined primarily by the differential filtration of fibrinogen and the various degradation products from the plasma through the glomerular basement membrane, which in turn is determined by the "pore size" of the basement membrane. In clinical nephrology measurement of the urinary F.D.P. level provides a rapid and convenient means of estimating the differential protein clearance.     

Increased urinary F2-isoprostane excretion in alcoholic liver disease

Free radical-induced lipid peroxidation (LP) is thought to be important in alcoholic liver disease (ALD), however, direct demonstration of increased LP in patients with ALD has been difficult. Quantification of F2-isoprostanes (F2-isoP), prostanoids produced by peroxidation of arachidonic acid, in plasma and urine are sensitive and specific indices of LP in vivo. To determine if LP is increased in ALD, 24-h urinary excretion of F2-isoPs were measured in 10 patients hospitalized because of ALD. The mean urinary excretion of the F2-isoP in the ALD patients' urine was 9.6+/-3.5 ng/mg creatinine, which was significantly elevated compared to controls' urinary excretion, which was 1.7+/-0.2 ng/mg creatinine (p<.01). The urinary excretion of F2-isoP decreased to 3.6+/-1.1 ng/mg creatinine as the patients improved clinically with abstinence over the 1-month period. These data suggest that lipid peroxidation, as assessed by this noninvasive method, is increased in patients with acute ALD and decreases with time as the patients improve clinically with abstinence.     

Effects of tripterine on mRNA expression of TGF-beta1 and collagen IV expression in BW F1 mice

Tripterine is a chemical isolated from a traditional Chinese herb which had been testified for its anti-inflammatory and immunosuppressive activities in a previous study. However, little is known about the effects and mechanism of action of Tripterine on treating lupus nephritis. In the present study we investigated the effect of Tripterine on the F1 hybrids of New Zealand Black (NZB) and New Zealand White (NZW) mice which functioned as a model of human systemic lupus erythematosus (BW F1 mice) and evaluated the possible mechanism implicated in the mRNA expression of TGF-beta1 and collagen IV expression of the BW F1 mice kidney tissue. Different doses of Tripterine were injected peritoneally to BW F1 mice at different stages to study the preventive effects of Tripterine on lupus nephritis glomerulosclerosis and its mechanisms. Twenty-four hour urine protein excretion, serum anti-dsDNA antibodies and the expression of collagen type IV were examined by immunohistochemistry while the expression of TGF-beta1 mRNA was detected by RT nested PCR. Tripterine decreased urine protein excretion and the level of serum anti-dsDNA antibodies and also suppressed the expression of collagen type IV and TGF-beta1 mRNA in the murine kidney tissue. Administration of Tripterine before the occurrence of proteinuria had much greater protective effects than if it was administered after the occurrence of proteinuria. No significant difference was found between the 3 mg/kg/week Tripterine-treated-group and the 6 mg/kg/week Tripterine-treated-group. Tripterine had a definite protective effect on glomerulosclerosis of the lupus murine model. Tripterine could significantly reduce the amount of urine protein excretion, suppress the formation of serum anti-dsDNA antibodies, it could also efficiently decrease the expression of renal collagen type IV probably due to its suppressive effect on the expressions of local TGF-(1 mRNA) in this model.     

Reduced urinary excretion of sulfated polysaccharides in diabetic rats

The aim of the present study was to further understand the changes in renal filtration that occur in the early stages of diabetes mellitus. Diabetes was induced in male Wistar rats by a single injection of streptozotocin. Glycemia, body weight, 24-h urine volume and urinary excretion of creatinine, protein and glycosaminoglycans were measured 10 and 30 days after diabetes induction. All the diabetic animals used in the present study were hyperglycemic, did not gain weight, and presented proteinuria and creatinine hyperfiltration. In contrast, the glycosaminoglycan excretion decreased. Dextran sulfates of different molecular weights (6.0 to 11.5 kDa) were administered to the diabetic rats, and to age-matched, sham-treated controls. Most of the dextran sulfate was excreted during the first 24 h, and the amounts excreted in the urine were inversely proportional to the dextran sulfate molecular weight for all groups. Nevertheless, diabetic rats excreted less and accumulated more dextran sulfate in kidney and liver, as compared to controls. These differences, which were observed only for the dextran sulfates of higher molecular weights (>7 kDa), increased with the duration of diabetes. Our findings suggest differential renal processing mechanisms for proteins and sulfated polysaccharides, with the possible involvement of kidney cells.     

Effect of indomethacin on proteinuria in rats with autologous immune complex nephropathy

Although non-steroidal anti-inflammatory agents have been used to reduce levels of urinary protein excretion in patients with the nephrotic syndrome, the general usefulness of these drugs in proteinuric states remains unclear. The present study was designed to confirm the efficacy and to investigate some of the mechanism/s of action of non-steroidal anti-inflammatory agents in animals with proteinuria as the result of a single form experimental renal disease. Autologous immune complex nephropathy was produced in groups of Lewis rats by the administration of autologous tubular Fx1A antigen. After marked proteinuria developed, indomethacin (8 mg/kg/day) was administered orally to one group of animals for five days while a control group received only vehicle. The level of urinary protein excretion in the indomethacin treated animals was 420 +/- 198 mg/day compared to a level of 1180 +/- 306 seen in the untreated animals (p less than 0.05). When the indomethacin-treated and control animals were compared, the reduction in proteinuria could not be found to be associated with a change in the glomerular filtration rate, urine electrolyte or osmolar excretion rates, electron microscopic appearance of the glomerular basement membrane, or a change in the glomerular permeability to neutral dextran. Treatment of animals with either sodium salicylate or lower does of indomethacin (both of which resulted also in significant falls in urinary prostaglandin E excretion rates) failed to reduce the levels of proteinuria. Thus, indomethacin was capable of reducing the levels of protein excretion in rats with autologous immune complex nephropathy although the mechanism of action of this agent remains unclear.