Evaluation of nephrotoxic effects of aristolochic acid on zebrafish (Danio rerio) larvae.

To analyze the toxic effects of aristolochic acid (AA) on developed kidneys in zebrafish larvae, zebrafish at 3 days postfertilization were treated with various concentrations of AA for 24 h before the status of kidney injury was investigated from several points of view. It was found that 21% of the larvae treated with 10 µmoL/L AA exhibited evident periocular edema. When the concentrations of AA were increased to 20 and 40 µmoL/L, defect in the cardiovascular system characterized by slow heart beat and blood flow was seen coupled with periocular edema. Creatinine in the whole larval tissue determined by liquid chromatography-mass spectrometry/mass spectrometry exhibited dramatic increase in the treated groups in a dose-dependent manner within a certain range of doses. Several evident protein bands were detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in supernatant of the treated larvae, indicating leakage of glomerular filtration barrier. Results of quantitative polymerase chain reaction show that the messenger RNA expression of nephrin in the 20 and 40 µmoL/L AA-treated groups decreased to 0.58 ± 0.062 and 0.37 ± 0.075-folds of the control, respectively. Kidney damage was further confirmed by the histological changes in paraffin sections of treated larvae, for example, cystic glomeruli and disorganized epithelia cells of pronephric tubules. Our results revealed that AA exerted toxic effects on developed kidney of zebrafish larvae in a dose-dependent manner and podocyte dysfunction may be involved in the kidney injury and proteinuria.

Association of proteinuria threshold in pre-eclampsia with maternal and perinatal outcomes: a nested case control cohort of high risk women.

OBJECTIVES: To evaluate occurrence of adverse maternal and perinatal outcomes with different thresholds of proteinuria (300-499 mg and ≥500 mg/24 hours) in pre-eclamptic women, comparing outcomes against women with chronic and gestational hypertension. DESIGN: Secondary analysis of the Vitamins in Pre-Eclampsia Trial. SETTING: 25 UK hospitals in ten geographical areas. POPULATION: 946 women with pre-existing risk factors for pre-eclampsia. METHODS: Women with pre-eclampsia and proteinuria 300-499 mg/24 h (PE300, referent group, n=60) or proteinuria ≥500 mg/24 h (PE500, n=161) were compared with two groups of non-proteinuric women with chronic hypertension (CHT, n=615) or gestational hypertension (GH, n=110). MAIN OUTCOME MEASURES: MATERNAL: progression to severe hypertension. Perinatal: small for gestational age (SGA) <5(th) centile, gestation at delivery. RESULTS: Severe hypertension occurred more frequently in PE500 (35%) and PE300 (27%) than CHT (5.9%; P≤0.01) and GH (10%; p≤0.001). Gestation at delivery was earlier in PE500 (33.2 w) than PE300 (37.3 w; P≤0.001), and later in CHT (38.3 w; P≤0.05) and GH (39.1 w; P≤0.001). SGA infants were more frequent in PE300 (32%) than in CHT (13.3%; P≤0.001) and GH (16.5%; P≤0.05). Women in PE500 were more likely to have a caesarean section than PE300 (78% vs. 48%; P≤0.001), and to receive magnesium sulphate (17% vs. 1.7%, P≤0.05). CONCLUSION: Women with PE300 have complication rates above those of women managed as out-patients (GH and CHT), meriting closer surveillance and confirming 300 mg/d as an appropriate threshold for determining in-patient management. Adverse perinatal outcomes are higher still in women with PE500.

Effects of Helicobacter pylori eradication on proteinuria: a prospective study.

BACKGROUND: Helicobacter pylori is one of the most common bacterial infections, seen in humans worldwide and its possible relationship to different diseases is a focus of attention nowadays. The aim of this study was to analyse the effects of H. Pylori eradication on proteinuria. METHODS: Ninety-nine patients suffering from dyspeptic complaints were recruited in this prospective study. The patients were divided into two groups according to the presence of H. pylori infection. Thus, a total of 67 H. pylori positive and 32 H. pylori negative patients were studied. The H. pylori positive patients' group was divided into two groups according to response toH. pylori eradication treatment. A total of three groups were formed, viz; group 1 comprises of patients who are H. pylori positive and responds positively toH. pylori eradication therapy, group 2 comprises of patients who are H. pylori positive and responds negatively toH. pylori eradication therapy and group 3 is the control group and comprises of patients that are H. pylori negative. Urine samples to obtain the protein/creatinine ratio were collected initially and at the end of the study from all patients. RESULTS: Mean difference levels (pre- and post-treatment difference) of urine protein/creatinine ratio was 0.055 ± 0.13 in group 1. The ratio was - 0.0007 ± 0.0067 in group 2 and - 0.0022 ± 0.008 in group 3. A statistically significant difference was found in group 1 compared to the other groups in terms of mean difference levels of protein/creatinine ratios (p < 0.001). CONCLUSION: As a result of our study, treatment of H. pylori eradication significantly reduced the proteinuria within the normal limits.