OBJECTIVE: To follow up the participants of the randomized clinical trial "Efficacy and Safety of Niaoduqing Particles () for Delaying Moderate-to-Severe Renal Dysfunction", and assess the long-term effects of Niaoduqing Particles on delaying the progression of renal dysfunction. METHODS: Participants, who had previously been randomly assigned to receive Niaoduqing Particles or placebo for 24 weeks (146 cases in each group), were invited to follow-up and all were administered Niaoduqing Particles 5 g thrice daily and 10 g before bedtime for 24 weeks. The primary endpoints were changes in baseline serum creatinine (Scr) and estimated glomerular filtration rate (eGFR) after completion of the open-label treatment period. RESULTS: After the double-blind period, the median (interquartile range) changes in Scr were 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) μmol/L for the Niaoduqing Particle and placebo groups, respectively (P=0.008), and the median changes in eGFRs were-0.2 (-4.3-2.7) and-2.21 (-5.7-0.8) mL•min•1.73 m, respectively (P=0.016). There were significant differences in the double-blind period changes in renal function between groups. After the open-label period, the median changes in Scr were 9.0 (-10.0-41.9) and 17.5 (-6.0-50.0) μmol/L for the Niaoduqing Particle and placebo groups according to baseline grouping, respectively (P=0.214), and the median changes in eGFRs were-2.3 (-6.4-1.9) and-3.7 (-7.5-1.1) mL•min•1.73 m, respectively (P=0.134). There were no statistical differences in the open-label period changes in renal function between groups. The eGFR reduction of participants who accepted Niaoduqing Particle treatment for 48 weeks was projected to 2.5 mL•min•1.73 m per year. CONCLUSION Niaoduqing Particles appear to have long-term efficacy for patients with moderate-to-severe renal dysfunction. Although there was no statistical difference, the early use of Niaoduqing Paticles seems to ameliorate the worsening of renal function. (Trial registration No. ChiCTR-TRC-12002448).
Adult ; Disease Progression ; Double-Blind Method ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Follow-Up Studies ; Glomerular Filtration Rate ; drug effects ; Humans ; Kidney Diseases ; drug therapy ; physiopathology ; Male ; Middle Aged ; Outcome Assessment (Health Care)

Cardiovascular disease is one of the most common complications and the main cause of death in patients with chronic kidney disease. Uremic toxins are the primary cause of cardiovascular disease in renal insufficiency. In patients with chronic kidney disease, the protein-bound uremic toxins represented by indoxyl sulfate are difficult to be removed by conventional dialysis and are extremely toxic. In recent years, studies have confirmed that the occurrence of cardiovascular disease induced by chronic kidney disease is closely related to the accumulation of indoxyl sulfate. Indoxyl sulfate can induce oxidative stress to cause endothelial injury, smooth muscle cell proliferation and migration, and promote the occurrence of atherosclerosis, thereby affecting multiple systems throughout the body. This article reviews the research progress of uremic toxin indoxyl sulfate in end-stage renal diseases associated cardiovascular diseases.
Cardiovascular Diseases ; complications ; physiopathology ; Humans ; Indican ; toxicity ; Kidney Failure, Chronic ; complications ; physiopathology ; Oxidative Stress ; Toxins, Biological ; toxicity

Kidney diseases are important causes of mortality world widely. Renal microvascular dysfunction plays a pivotal role in the development of kidney diseases. Pharmacological and biochemical tools have been used to conduct detailed studies on the metabolization of arachidonic acid by cytochrome P450 (CYP450) in renal microvasculature. CYP450 epoxygenase metabolites epoxyeicosatrienoic acids (EETs) are mainly produced in renal microvessels. EETs exhibit renoprotective effects through vasodilation, anti-hypertension, anti-apoptosis and anti-inflammation, and were reported as therapeutic targets of renal diseases. However, the ability of the kidney in generating EETs is reduced in renal diseases. Recently, the studies from transgenic animal overexpressing CYP450 epoxygenases and application of soluble epoxide hydrolase inhibitors revealed that increasing of EETs exhibits renoprotective effects in vivo. The present review focuses on the protective mechanisms of EETs in kidney physiology and diseases.
Animals ; Animals, Genetically Modified ; Arachidonic Acid ; metabolism ; Cytochrome P-450 Enzyme System ; physiology ; Disease Models, Animal ; Humans ; Inflammation ; Kidney ; physiology ; Kidney Diseases ; physiopathology ; Vasodilation

Cofilin is a actin-binding protein in eukaryotic cells. It plays a role in maintaining the steady state of the internal environment through regulating actin dynamics, which contributes to the development of various kinds of diseases. In recent 20 years, cofilin has been widely attracted due to its regulatory effect on cell phenotype, gene transcription, apoptosis and inflammation in renal tissue. Cofilin plays a regulatory role in pathological changes in proteinuria diseases such as minimal change nephropathy, focal segmental glomerulosclerosis, membranous nephropathy, and IgA nephropathy. It could be one of the diagnosis index for glomerular podocyte injury. At the same time, cofilin plays a key role in maintaining the polarity and function of proximal tubular epithelial cells and it is involved in the regulation of kidney inflammation in a variety of kidney diseases, such as renal ischemia/reperfusion injury, diabetic nephropathy, and hypertensive nephropathy reaction. In addition, cofilin plays an important role in epithelial-to-mesenchymal transition (EMT) of tumor cells and epithelial cells in various tissues, suggesting that cofilin may be involved in the regulation of peritoneal dialysis-related EMT and fibrosis. Cofilin might turn into the new diagnosis and treatment target of kidney diseases.
Cofilin 1 ; metabolism ; Glomerulosclerosis, Focal Segmental ; physiopathology ; Humans ; Kidney ; physiopathology ; Kidney Diseases ; physiopathology ; Proteinuria ; genetics ; physiopathology

BACKGROUNDAtherosclerosis (AS) is an inflammatory disease. Inflammation was considered to play a role in the whole process of AS. This study aimed to analyze the relationships of inflammatory factors and risk factors with different target organ damages (TOD) in essential hypertension (EH) patients and to explore its clinical significance.

METHODSA total of 294 EH patients were selected and divided into four groups according to their conditions of TOD. Forty-eight healthy subjects were selected as control. The clinical biochemical parameters, serum amyloid A, serum tryptase, and lipoprotein-associated phospholipase A2 (Lp-PLA2) in each group were detected, and the related risk factors were also statistically analyzed.

RESULTSFibrinogen (Fbg) was the most significant independent risk factor in acute coronary syndrome (ACS) group (odds ratio [OR]: 22.242, 95% confidence interval [CI]: 6.458-76.609, P< 0.001) with the largest absolute value of the standardized partial regression coefficient B' (b': 1.079). Lp-PLA2 was the most significant independent risk factor in stroke group (OR: 13.699, 95% CI: 5.236-35.837, P< 0.001) with b' = 0.708. Uric acid (UA) was the most significant independent risk factor in renal damage group (OR: 15.307, 95% CI: 4.022-58.250, P< 0.001) with b' = 1.026.

CONCLUSIONSFbg, Lp-PLA2, and UA are the strongest independent risk factors toward the occurrence of ACS, ischemic stroke, and renal damage in EH patients, thus exhibiting the greatest impacts on the occurrence of ACS, ischemic stroke, and renal damage in EH patients, respectively.

1-Alkyl-2-acetylglycerophosphocholine Esterase ; Aged ; Antihypertensive Agents ; therapeutic use ; Enzyme-Linked Immunosorbent Assay ; Essential Hypertension ; blood ; complications ; drug therapy ; physiopathology ; Female ; Humans ; Kidney Diseases ; blood ; etiology ; physiopathology ; Logistic Models ; Male ; Middle Aged ; Renal Insufficiency, Chronic ; blood ; etiology ; physiopathology ; Risk Factors ; Serum Amyloid A Protein ; metabolism ; Stroke ; blood ; etiology ; physiopathology ; Tryptases ; blood

OBJECTIVETo observe the effect of Trichinella spiralis and its worm-derived proteins on cecal ligation and puncture (CLP)-induced sepsis in mice.

METHODSEighty male BALB/c mice were randomly divided into sham-operated group, CLP group, Trichinella spiralis muscle larvae (ML) pre-infection group (ML+CLP group), soluble muscle larvae proteins (SMP) treatment group (SMP+CLP group) and excretory-secretory proteins (MES) treatment group (MES+CLP group). In ML+CLP group, the mice were orally infected with 300 Trichinella spiralis muscle larvae at 28 days before CLP and those in the other groups were intraperitioneally injected with PBS or SMP (25 µg/mice) or MES (25µg/mice) 30 min after CLP. The general condition and 72-h survival after CLP of the mice were observed. The levels of alanine transaminase (ALT), aspartate transaminase (AST), blood urea nitrogen (BUN), creatinine (Cr), TNF-α, IL-6, IL-1β, IL-10 and TGF-β were measured at 12 h after the operation, and the pathological changes of the liver and kidney were observed.

RESULTSs Compared with the sham-operated mice, the mice in CLP group showed decreased 72-h survival, obviously increased ALT, AST, BUN, Cr, TNF-α, IL-6, IL-1β, IL-10, and TGF-β with hepatic cords disorder, hepatocytes swelling, glomerulus shrinkage, and renal tubular cell edema. Compared with CLP group, the mice in ML+CLP group showed lowered levels of ALT, AST, Cr, TNF-α and IL-1β and increased levels of IL-10 and TGF-β; in SMP+CLP group, the levels of ALT, AST, Cr, TNF-α and IL-1β were decreased and TGF-β increased. In MES+CLP group, the mice showed obviously increased 72-h survival with lowered levels of ALT, AST, BUN, Cr, TNF-α, IL-6 and IL-1β, increased levels of IL-10 and TGF-β, and alleviated liver and kidney damages.

CONCLUSIONTrichinella spiralis and its worm-derived proteins can decrease the levels of pro-inflammatory cytokines and increase immunomodulatory cytokines, and MES has more potent effect to reduce structural and functional damages of the liver and kidney.

Alanine Transaminase ; blood ; Animals ; Antigens, Helminth ; pharmacology ; Aspartate Aminotransferases ; blood ; Blood Urea Nitrogen ; Cecum ; Creatinine ; blood ; Cytokines ; blood ; Helminth Proteins ; pharmacology ; Kidney ; physiopathology ; Kidney Diseases ; therapy ; Ligation ; Liver ; physiopathology ; Liver Diseases ; therapy ; Male ; Mice ; Mice, Inbred BALB C ; Sepsis ; therapy ; Trichinella spiralis

PURPOSE: Endothelial dysfunction (ED) is a pivotal phenomenon in the development of cardiovascular disease (CVD) in patients receiving hemodialysis (HD). Indoxyl sulfate (IS) is a known uremic toxin that induces ED in patients with chronic kidney disease. The aim of this study was to investigate whether AST-120, an absorbent of IS, improves microvascular or macrovascular ED in HD patients. MATERIALS AND METHODS: We conducted a prospective, case-controlled trial. Fourteen patients each were enrolled in respective AST-120 and control groups. The subjects in the AST-120 group were treated with AST-120 (6 g/day) for 6 months. Microvascular function was assessed by laser Doppler flowmetry using iontophoresis of acetylcholine (Ach) and sodium nitroprusside (SNP) at baseline and again at 3 and 6 months. Carotid arterial intima-media thickness (cIMT) and flow-mediated vasodilation were measured at baseline and 6 months. The Wilcoxon rank test was used to compare values before and after AST-120 treatment. RESULTS: Ach-induced iontophoresis (endothelium-dependent response) was dramatically ameliorated at 3 months and 6 months in the AST-120 group. SNP-induced response showed delayed improvement only at 6 months in the AST-120 group. The IS level was decreased at 3 months in the AST-120 group, but remained stable thereafter. cIMT was significantly reduced after AST-120 treatment. No significant complications in patients taking AST-120 were reported. CONCLUSION: AST-120 ameliorated microvascular ED and cIMT in HD patients. A randomized study including a larger population will be required to establish a definitive role of AST-120 as a preventive medication for CVD in HD patients.
Acetylcholine ; Adult ; Carbon/*therapeutic use ; Cardiovascular Diseases/etiology/*prevention & control ; Carotid Intima-Media Thickness ; Endothelium, Vascular/*physiopathology ; Female ; Humans ; Iontophoresis ; Kidney Failure, Chronic/complications/*physiopathology/*therapy ; Laser-Doppler Flowmetry ; Male ; Microcirculation/physiology ; Middle Aged ; Nitroprusside ; Oxides/*therapeutic use ; Prospective Studies ; *Renal Dialysis ; Young Adult

To examine levels of M-type phospholipase A2 receptor (PLA2R) and its antibody in the patients with hepatitis B virus-associated membranous nephropathy (HBV-MN), and to explore the correlation of PLA2R with laboratory parameters and pathological characteristics.
 Methods: A total of 49 adult patients with biopsy-proved HBV-MN were enrolled in this study. Levels of anti-PLA2R antibody in serum and PLA2R in renal tissue were detected. Patients were assigned into two groups: a positive PLA2R group and a negative PLA2R group. Differences in laboratory parameters and pathological characteristics were compared between the two groups.
 Results: Of 49 patients with HBV-MN, 17 had positive PLA2R expression in renal tissues. In the positive PLA2R group, 10 patients were positive for serum anti-PLA2R antibody. Patients with positive PLA2R expression in renal tissues showed higher levels of 24 hour urinary protein [(4.6±3.9) g/d], serum HbsAg (70.5%) and renal HbsAg expression (71%), while lower level of serum albumin [(24.1±7.5) g/L] than those of the negative group.
 Conclusion: PLA2R is expressed in the renal tissues and serum anti-PLA2R antibody can be detected in some HBV-MN patients. Positive PLA2R expression in renal tissue might be related to HbsAg deposition in serum and renal tissues. Patients with positive PLA2R expression in renal tissue have more severe glomerular sclerosis.
Adult ; Antibodies ; Autoantibodies ; genetics ; physiology ; Biopsy ; Glomerulonephritis, Membranous ; complications ; etiology ; genetics ; Hepatitis B ; complications ; Hepatitis B Surface Antigens ; adverse effects ; Hepatitis B virus ; Humans ; Kidney ; blood supply ; chemistry ; physiopathology ; Kidney Diseases ; etiology ; genetics ; physiopathology ; Male ; Prognosis ; Proteinuria ; epidemiology ; genetics ; Receptors, Phospholipase A2 ; blood ; physiology ; Serum Albumin ; genetics

Elucidation of the efficacy of traditional Chinese medicine (TCM) is of importance for scientists of modern medicine to understand the value of TCM clinical experience, and it is necessary to have a biological language to scientifically describe the efficacy of TCM. With this background?Chinmedomics has been proposed by our team, which includes integrating serum pharmacochemistry and metabolomics technology, defining theory and research methods for expressing the efficacy of TCMs based on the biomarkers discovery of TCM syndrome and elucidating the efficacy of TCM formulae, discovering effective constituents, and finally elucidating the scientific value of TCM. In the present study, the innovative chinmedomics strategy was conducted to evaluate the therapeutic effects of ShenQiWan (SQW) acting on ShenYangXu (kidney-yang deficiency syndrome, KYDS). We analyzed the urine metabolic trajectory between the model and control groups, and identified the biomarkers by the multivariate analysis. We found that SQW caused significant restoration of abnormal metabolism of KYDs. Using the method of metabolomics, 17 potential urine biomarkers were analyzed through 4 repeated tests in our serial studies on SQW and KYDS. Under the premise of therapeutic efficacy, a total of 56 peaks were tentatively characterized in vivo by the use of serum pharmacochemistry. Correlation analysis between marker metabolites and in vivo constituents of SQW showed that 28 compositions had a close relationship with urine biomarkers of therapeutic effects, whichmight play a key role in the therapeutic effect of SQW. These compounds were imported into an online database to predict their targets. Twenty-three important potential targets were identified, which were related to the metabolism of steroid hormone, tryptophan utilization, and thyroid hormone. In conclusion, chinmedomics is a useful strategy for discovery of potentially effective constituents from complex TCM formulae.
Animals ; Biomarkers ; urine ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Kidney ; drug effects ; physiopathology ; Kidney Diseases ; drug therapy ; physiopathology ; urine ; Male ; Metabolomics ; methods ; Yang Deficiency ; drug therapy ; physiopathology ; urine

To assess the neurotoxic effects and redox responses of Aroclor 1254 (A1254) on perinatally exposed rat offspring, A1254 was administered by gavage from gestational day (GD) 6 to postnatal day (PND) 21. Neurobehavioral development, antioxidant enzyme activities, lipid peroxidation (LPO), nitric oxide (NO), and NO synthase (NOS) levels were analyzed in the offspring. Neurobehavioral development analysis revealed delayed appearance of the righting reflex, negative geotaxis, and cliff drop test responses in A1254 exposed group. Developmental A1254 exposure also caused oxidative stress in the brain of PND 22 offspring via reductions in the activity of SOD and GSH-Px, and by promoting a rise in the levels of NO and NOS.
Aging ; metabolism ; Animals ; Cerebral Cortex ; drug effects ; enzymology ; metabolism ; Chlorodiphenyl (54% Chlorine) ; toxicity ; Female ; Glutathione Peroxidase ; metabolism ; Kidney ; drug effects ; enzymology ; metabolism ; Lipid Peroxidation ; drug effects ; Liver ; drug effects ; enzymology ; metabolism ; Mice ; Nervous System ; drug effects ; growth & development ; metabolism ; physiopathology ; Nervous System Diseases ; chemically induced ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Oxidative Stress ; drug effects ; Pregnancy ; Prenatal Exposure Delayed Effects ; chemically induced ; Random Allocation ; Rats ; Superoxide Dismutase ; metabolism