OBJECTIVE: To assess the risk of aristolochic acid (AA)-associated cancer in patients with AA nephropathy (AAN). METHODS: A retrospective study was conducted on patients diagnosed with AAN at Peking University First Hospital from January 1997 to December 2014. Long-term surveillance and follow-up data were analyzed to investigate the influence of different factors on the prevalence of cancer. The primary endpoint was the incidence of liver cancer, and the secondary endpoint was the incidence of urinary cancer during 1 year after taking AA-containing medication to 2014. RESULTS: A total of 337 patients diagnosed with AAN were included in this study. From the initiation of taking AA to the termination of follow-up, 39 patients were diagnosed with cancer. No cases of liver cancer were observed throughout the entire follow-up period, with urinary cancer being the predominant type (34/39, 87.17%). Logistic regression analysis showed that age, follow-up period, and diabetes were potential risk factors, however, the dosage of the drug was not significantly associated with urinary cancer. CONCLUSIONS No cases of liver cancer were observed at the end of follow-up. However, a high prevalence of urinary cancer was observed in AAN patients. Establishing a direct causality between AA and HCC is challenging.
Humans ; Retrospective Studies ; Incidence ; Carcinoma, Hepatocellular ; Liver Neoplasms/epidemiology* ; Kidney Diseases/chemically induced* ; Aristolochic Acids/adverse effects*

Objective: To explore the expulsion effect of sodium dimercaptopropanesulfonate (DMPS) on mercury in different organs of mercury poisoning and the therapeutic effect of glutathione (GSH) combined with antioxidant therapy on mercury poisoning. Methods: In February 2019, 50 SPF male SD rats were randomly divided into 5 groups, 10 rats in each group: A (saline negative control group) , B (HgCL2 positive control group) , treatment group (C: intramuscular injection of DMPS 15 mg/kg treatment, D: intramuscular injection of DMPS30 mg/kg treatment, E: intramuscular injection of DMPS 15 mg/kg and intraperitoneal injection of GSH200 mg/kg treatment) . Rats in group B, C, D and E were subcutaneously injected with mercury chloride solution (1 mg/kg) to establish a rat model of subacute mercury poisoning kidney injury. Rats in group A were subcutaneously injected with normal saline. After the establishment of the model, rats in the treatment group were injected with DMPS and GSH. Rats in group A and group B were injected with normal saline. At 21 d (treatment 7 d) and 28 d (treatment 14 d) after exposure, urine and blood samples of 5 rats in each group were collected. Blood biochemistry, urine mercury, urine microalbumin and mercury content in renal cortex, cerebral cortex and cerebellum were detected. Results: After exposure to mercury, the contents of mercury in renal cortex, cerebrum and cerebellum of rats in group B, C, D and E increased, and urine microalbumin increased. Pathology showed renal tubular injury and renal interstitial inflammation. Compared with group B, urinary mercury and renal cortex mercury in group C, D and E decreased rapidly after DMPS treatment, and there was no significant decrease in mercury levels in cerebellum and cerebral cortex of rats, accompanied by transient increase in urinary albumin after DMPS treatment (P<0.05) ; the renal interstitial inflammation in group E was improved after GSH treatment. There was a positive correlation between urinary mercury and the contents of mercury in renal cortex, cerebral cortex and cerebellum (r=0.61, 0.47, 0.48, P<0.05) . Conclusion: DMPS mercury expulsion treatment can significantly reduce the level of metal mercury in the kidney, and there is no significant change in the level of metal mercury in the cortex and cerebellum.
Animals ; Brain/drug effects* ; Glutathione ; Inflammation ; Kidney/drug effects* ; Kidney Diseases/chemically induced* ; Male ; Mercuric Chloride/therapeutic use* ; Mercury/urine* ; Mercury Poisoning/drug therapy* ; Rats ; Rats, Sprague-Dawley ; Saline Solution/therapeutic use* ; Unithiol/therapeutic use*

Colchicine plays an important role in the treatment of gout and some other diseases. Besides gastrointestinal symptoms, myopathy has been reported as a rare side effect of colchicine in some patients. We report a case of myopathy in a patient with chronic kidney disease caused by high-dose colchicine, and then review literature on colchicine-induced myopathy, so as to provide some experience for the clinical diagnosis, treatment and medication safety. A 51-year-old male patient with 10 years of gout and 5 years of chronic kidney disease history and irregular treatment was admitted to the hospital with complaint of recurrent left wrist arthralgia and emerging lower extremities myalgia after intake of 40-50 mg colchicine in total within 20 days. Laboratory examinations showed significantly increased creatine kinase (CK) and then colchicine-induced myopathy was diagnosed preliminarily. After withdrawl of colchicine and implementation of hydration, alkalization and intramuscular injection of compound betamethasone, the symptoms of arthralgia and myalgia were relieved within 3 days and CK decreased to normal range gradually. According to literature reports, colchicine related myopathy was mostly characterized by proximal myasthenia and myalgia, accompanied by elevated CK level, which usually occurred days to weeks after initial administration of colchicine at the usual dosage in patients with renal impairment or a change in the underlying disease state in those receiving long-term therapy, and the features might remit within three to four weeks after the drug was discontinued. Electromyography of proximal muscles showed myopathy marked by abnormal spontaneous activity and muscle pathology waa marked by accumulation of lysosomes and autophagic vacuoles. Chronic kidney disease, liver cirrhosis, higher colchicine dose and concomitant cytochrome P450 3A4 (CYP3A4) inhibitors were associated with increased risk of myo-pathy. Based on the similar efficacy and lower adverse reaction rate compared with larger dosage, small dose of colchicine was recommended by many important current guidelines and recommendations in the treatment of gout. In consideration of potential risks, colchicine should be used with caution in patients with kidney or liver impairment, and in those taking CYP3A4 or P-glycoprotein inhibitors. For those patients, the drug dose should be adjusted and the latent adverse reactions should be monitored carefully.
Colchicine/adverse effects* ; Gout/drug therapy* ; Humans ; Kidney ; Male ; Middle Aged ; Muscular Diseases/chemically induced* ; Renal Insufficiency, Chronic/complications*

To systemically evaluate the efficacy and safety of salvianolate intravenous drip in combination with hydration against contrast-induced nephropathy( CIN),and guide clinical medication. Chinese and English databases( PubMed,EMbase,the Cochrane Library,CBM,VIP,Wan Fang database,CNKI) were retrieved to collect the randomized controlled trials( RCTs) about the efficacy of salvianolate intravenous drip in combination with hydration( trial group) vs routine hydration( control group) in the prevention of contrastinduced nephropathy. The methodological quality of the RCTs was evaluated by using the Cochrane 5. 1. 0 Bias Risks Assessment Tool.The data were extracted and Meta-analysis was conducted by Reviewer Manager 5. 3. Egger's test and non-parametric clipping method were used to evaluate publication bias. A total of 9 RCTs with 2 186 participants were included. RESULTS:: of Meta-analysis showed that the incidence of contrast-induced nephropathy of trial group was significantly higher than that of control group( RR = 0. 46,95% CI[0. 35,0. 59],P<0. 001). Subgroup analysis showed that the incidences of CIN in patients with acute coronary syndrome( ACS) undergoing PCI,in patients with the average age≥65 years,in patients who received mean contrast volume ≥200 m L,in patients with serum creatinine( Scr) ≥ 80 μmol,or in patients who received intraoperative administration of salvianolate or PCI were higher than those in control group,with statistically significant differences( P<0. 05). The experimental group was superior to the control group in improving the indexes of renal function after operation,and the difference was statistically significant( P<0. 05). No study reported the incidence of adverse reactions( ADRs). The funnel plots of the incidence of CIN showed potential publication bias. The results of Egger's linear regression showed that there was certain publication bias. Sensitivity analysis,funnel plot,and " trim and fill" showed that the results of this study were stable and reliable. Salvianolate combined with routine hydration showed definite clinical efficacy in the prevention of contrast-induced nephropathy. However,exact conclusion should be further verified by additional high-quality,multi-centre,and large-scale RCT studies.
Contrast Media ; adverse effects ; Humans ; Kidney Diseases ; chemically induced ; prevention & control ; Percutaneous Coronary Intervention ; Plant Extracts ; therapeutic use ; Randomized Controlled Trials as Topic

BACKGROUND: In health examinations for local inhabitants in cadmium-polluted areas, only healthy people are investigated, suggesting that patients with severe cadmium nephropathy or itai-itai disease may be overlooked. Therefore, we performed hospital-based screening to detect patients with cadmium nephropathy in two core medical institutes in cadmium-polluted areas in Akita prefecture, Japan. METHODS: Subjects for this screening were selected from patients aged 60 years or older with elevated serum creatinine levels and no definite renal diseases. We enrolled 35 subjects from a hospital in Odate city and 22 from a clinic in Kosaka town. Urinary ß-microglobulin and blood and urinary cadmium levels were measured. RESULTS: The criteria for renal tubular dysfunction and the over-accumulation of cadmium were set as a urinary ß-microglobulin level higher than 10,000 μg/g cr. and a blood cadmium level higher than 6 μg/L or urinary cadmium level higher than 10 μg/g cr., respectively. Subjects who fulfilled both criteria were diagnosed with cadmium nephropathy. Six out of 57 patients (10.5% of all subjects) had cadmium nephropathy. CONCLUSIONS: This hospital-based screening is a very effective strategy for detecting patients with cadmium nephropathy in cadmium-polluted areas, playing a complementary role in health examinations for local inhabitants. REGISTRATION NUMBER No. 6, date of registration: 6 June, 2010 (Akita Rosai Hospital), and No. 1117, date of registration: 26 December, 2013 (Akita University).
Aged ; Aged, 80 and over ; Cadmium ; adverse effects ; urine ; Cadmium Poisoning ; blood ; complications ; urine ; Creatinine ; urine ; Environmental Exposure ; adverse effects ; Environmental Monitoring ; Environmental Pollutants ; adverse effects ; urine ; Female ; Hospitals ; Humans ; Japan ; Kidney Diseases ; chemically induced ; urine ; Male ; Middle Aged ; Sex Distribution

Metformin is a kind of biguanide hypoglycemic agent that has been widely used in patients with diabetes mellitus. In clinical practice, whether metformin should be stopped before Fundus fluorescein angiography (FFA) remains largely unclear. Some endocrinologists suggest stop metformin before FFA. However, ophthalmologists do not always adopt this opinion in their practice. This situation may lead to disputes between physicians and patients. This article analyzed contrast-induced nephropathy(CIN) and the related contrast agent, as well as the adverse reactions of fluorescein angiography. It pointed out that the discrepancy may be caused by misunderstanding of contrast agents used in FFA. For angiography using iodine contrast agent, metformin must be stopped because of the increased possibility of CIN, while for FFA using fluorescein sodium, no CIN has been reported yet. Therefore, the authors believe FFA is safe for diabetic patients with oral metformin and it is unnecessary to stop metformin before the examination.
Administration, Oral ; Contrast Media ; adverse effects ; Diabetes Mellitus, Type 2 ; diagnostic imaging ; drug therapy ; Diabetic Retinopathy ; diagnostic imaging ; Fluorescein Angiography ; adverse effects ; methods ; Humans ; Hypoglycemic Agents ; therapeutic use ; Kidney Diseases ; chemically induced ; Metformin ; therapeutic use

The aim of the present study is to evaluate the ability and mechanism by which grape seed procyanidin extract (GSPE) relieves arsenic trioxide (As2O3)-induced renal inflammatory injury. Therefore, male Kunming mice were treated with As2O3 and/or GSPE by gavage for 5 weeks. Mice were then sacrificed and inflammatory cytokines of kidneys were examined by ELISA, whereas the expression levels of molecules involved in the nuclear factor (NF)-κB signaling pathway were evaluated by both qRT-PCR and Western blot. Our results indicate that GSPE prevents As2O3-mediated renal inflammatory injury by inhibiting activation of the NF-κB signaling pathway and inflammatory cytokine production, while promoting expression of anti-inflammatory cytokines.
Animals ; Arsenic ; toxicity ; Grape Seed Extract ; therapeutic use ; Inflammation ; chemically induced ; drug therapy ; Kidney Diseases ; chemically induced ; drug therapy ; Male ; Mice ; Proanthocyanidins ; therapeutic use

OBJECTIVETo investigate the effects of Huaiqihuang Granules (, HQH), a mixture of Chinese herbs including Trametes robiniophila Murr, Fructus Lycii and Polygonatum sibiricum, on adriamycininduced nephropathy (ADRN) in rats and its underlying mechanisms.

METHODSRats with ADRN were divided into four groups: the sham group, the model group (distilled water), the low-dose HQH-treated (2 g/kg) group, and the high-dose HQH-treated (4 g/kg) group. Body weight and 24-h urinary protein (Upro) were checked every week. After 5-week intervention, at the end of the study, the rats were sacrificed and blood samples were collected for examination of biochemical parameters, including glomerular morphological makers, podocyte shape, cellular apoptosis, expressions of nephrin, inflammatory and apoptosis markers.

RESULTSHQH ameliorated the rat's general status, proteinuria, renal morphological appearance and glomerulosclerosis. The decreased expression of nephrin in ADRN rats was increased by HQH, as well as the impaired podocyte foot process fusion. Cytosolic levels of p65 and inhibitor of nuclear factor κBα (IκBα) were decreased in ADRN rats, and recovered by the treatment of HQH. Consistently, the induced expression of tumor necrosis factor α (TNF-α), phosphorylated nuclear factor κB p65 (p-NFκB p65) and IκBα in ADRN were markedly suppressed by HQH. In addition, induction of Bax, cleaved caspase-3 and cytochrome C in ADRN rats were suppressed by HQH, indicating the amelioration of apoptosis.

CONCLUSIONHQH could ameliorate renal impairments in ADRN rats by increasing nephrin expression, inhibiting NF-κB signaling pathway via the down-regulation of p-NF-κB p65 and p-IκBα, and suppression of glomerular and tubular apoptosis.

Animals ; Apoptosis ; drug effects ; Body Weight ; drug effects ; Caspase 3 ; metabolism ; Chromatography, High Pressure Liquid ; Cytochromes c ; metabolism ; Doxorubicin ; adverse effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Kidney ; drug effects ; pathology ; Kidney Diseases ; blood ; chemically induced ; complications ; drug therapy ; Kidney Glomerulus ; drug effects ; pathology ; ultrastructure ; Kidney Tubules ; drug effects ; pathology ; ultrastructure ; Male ; Membrane Proteins ; metabolism ; NF-KappaB Inhibitor alpha ; metabolism ; NF-kappa B ; metabolism ; Organ Size ; drug effects ; Proteinuria ; blood ; complications ; drug therapy ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Transcription Factor RelA ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism ; bcl-2-Associated X Protein ; metabolism

To discover the nephroprotective substances from Huangkui capsule.The components of Huangkui capsule were isolated by preparative liquid chromatography, and the active components were screened by LC/MS and identified. The adriamycine-injured HK-2 cells were treated with various active components with different concentrations, and the malonaldehyde (MDA) content, adenosine triphosphate (ATP) level and mitochondrial oxygen consumption rate were measured to verify the protective activity of the compounds.Four active components in Huangkui capsule were identified to exert nephroprotective effects. Fifteen flavanoids from these four components were tentatively identified by LC/MS, and hyperin, myricetin, quercetin, rutin and isoquercetin were confirmed. Hyperin, myricetin quercetin and rutin showed dose-dependent protective effects on injured HK-2 cells. Espacially, hyperin significantly reduced MDA content, quercetin and rutin significantly increased ATP level, and myricetin significantly increased mitochondrial oxygen consumption rate.Hyperin, myricetin, querctein and rutin might be the potential nephroprotective compounds in Huangkui capsule, their effects may be related to the inhibition of lipid peroxidation and the alleviation of mitochondrial damage.
Abelmoschus ; chemistry ; drug effects ; Adenosine Triphosphate ; metabolism ; Cell Line, Transformed ; Chromatography, Liquid ; Doxorubicin ; Drugs, Chinese Herbal ; Epithelial Cells ; drug effects ; Flavonoids ; pharmacology ; Kidney Diseases ; chemically induced ; drug therapy ; prevention & control ; Kidney Tubules, Proximal ; drug effects ; Lipid Peroxidation ; drug effects ; Malondialdehyde ; metabolism ; Mass Spectrometry ; Mitochondria ; drug effects ; Oxygen Consumption ; drug effects ; Protective Agents ; chemistry ; pharmacology ; Quercetin ; analogs & derivatives ; pharmacology ; Rutin ; pharmacology

The present study was designed to determine the mechanism underlying the treatment of nephrotic syndrome using astragaloside by observing the effects of astragaloside on the expression of nephrin and podocin proteins and genes in kidneys of rats with adriamycin nephropathy. The rats were injected with adriamycin and, after successful model establishment, randomly divided into a model group, a Methylprednisolone (MP) group, and an astragaloside group. The 24-h complete urine samples were collected. Biochemical indicators were monitored, and kidney tissues were collected for pathological analysis using light microscopy and electron microscopy. The mRNA expression of nephrin and podocin was measured in the kidney tissues using the real-time qPCR, and the protein expression levels of nephrin and podocin were detected using Western blot analysis. At the end of 12 weeks of drug intervention, the urinary protein level was lower in the MP and astragaloside groups than that in the model group (P = 0.008 and P = 0.01, respectively). Serum albumin was higher in the MP and astragaloside groups than in the model group (P < 0.001 and P = 0.012, respectively). Podocytes in the MP group were nearly normal, and fusion of podocytes in the astragaloside group was significantly less than that in the control group. The nephrin and podocin mRNA and protein expression levels in the intervention groups were higher (P < 0.05) than that in the model group. Due to the increased expression of podocyte-related nephrin and podocin proteins, astragaloside maintained slit diaphragm integrity and decreased the level of proteinuria in rats with adriamycin nephropathy.
Animals ; Astragalus Plant ; chemistry ; Doxorubicin ; adverse effects ; Drugs, Chinese Herbal ; administration & dosage ; Glucosides ; administration & dosage ; Humans ; Kidney ; drug effects ; metabolism ; Kidney Diseases ; chemically induced ; drug therapy ; Male ; Podocytes ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar