OBJECTIVETo evaluate the renal protective effect of Tangshenkang Granule () in a rat model of diabetic nephropathy (DN).

METHODSForty male Sprague-Dawley rats were randomly divided into control, DN, Tangshenkang and benazepril groups. DN model was established in the rats of DN, Tangshenkang and benazepril groups. Tangshenkang Granule solution and benazepril hydrochloride solution were intragastrically administered daily to the rats in the Tangshenkang and benazepril groups for 8 weeks, respectively. Urinary albumin and creatinine were detected. The albumin/creatinine (ACR) was calculated in addition to 24 h urinary protein (24-h UPr), serum creatinine (Scr), blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and creatinine clearance rate (Ccr). Right kidneys were harvested for pathological observation using periodic acid-silver methenamine-Masson staining. The average glomerular diameter (DG), average glomerular (AG) and mesangial areas (AM) were measured. The thickness of glomerular basement membrane (TGBM) was detected using transmission electron microscope.

RESULTSCompared with rats in the control group, rats in the DN group showed significantly decreased body weight, increased hypertrophy index, 24-h urinary volume, 24-h UPr, ACR, Scr, BUN, Ccr, blood lipids as well as renal pathological indices including DG, AG, AM, AM/AG and TGBM (P <0.05). Compared with the DN group, the weights of rats in the Tangshenkang and benazepril groups were significantly increased, and the renal hypertrophy indices were significantly decreased (P <0.05). The 24-h urinary volumes, ACR, 24-h UPr, Scr, BUN, Ccr, LDL, DG, AG, AM and TGBM were obviously decreased (P <0.05). Compared with the benazepril group, the Tangshenkang group showed significantly decreased levels of ACR, 24-h UPr, AG and AM (P <0.05).

CONCLUSIONSTangshenkang Granule decreased the urinary protein, attenuated the high glomerular filtration rate and improved lipid metabolism in DN rats, and prevented further injury induced by diabetic nephropathy.

Albuminuria ; complications ; Animals ; Basement Membrane ; drug effects ; metabolism ; Blood Urea Nitrogen ; Body Weight ; drug effects ; Creatinine ; blood ; urine ; Diabetic Nephropathies ; blood ; drug therapy ; physiopathology ; urine ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Hypertrophy ; Kidney Function Tests ; Kidney Glomerulus ; drug effects ; pathology ; physiopathology ; Lipid Metabolism ; drug effects ; Lipids ; blood ; Male ; Rats, Sprague-Dawley

Background: The nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3) inflammasome composed of NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), and caspase-1 is engaged in the inflammatory response of many kidney diseases and can be activated by purinergic 2X7 receptor (P2X7R). This study was conducted to explore whether P2X7R plays a pathogenic role in the podocyte damage of obesity-related glomerulopathy (ORG) and whether this role is mediated by the activation of NLRP3 inflammasome. Methods: A mouse model of ORG was established by high-fat diet feeding. The conditionally immortalized mouse podocytes were cultured with leptin or with leptin and P2X7R antagonist (KN-62 or A438079). The mRNA and protein expression of the P2X7R and NLRP3 inflammasome components including NLRP3, ASC, and caspase-1, as well as the podocyte-associated molecules including nephrin, podocin, and desmin in mouse renal cortex or cultured mouse podocytes were tested by real-time-polymerase chain reaction and Western blot analysis, respectively. Results: The significantly upregulated expression of P2X7R and NLRP3 inflammasome components and the NLRP3 inflammasome activation were observed in the renal cortex (in fact their location in podocytes was proved by confocal microscopy) of ORG mice in vivo, which were accompanied with the morphological changes of podocyte damage and the expression changes of podocyte-associated molecules. Similar changes in the expression of P2X7R and NLRP3 inflammasome components as well as in the expression of podocyte-associated molecules were also observed in the cultured podocyte studies treated by leptin in vitro, and all of the above changes were significantly attenuated by the P2X7R antagonist KN-62 or A438079. Conclusions P2X7R could trigger the activation of NLRP3 inflammasome, and the activated P2X7R/NLRP3 inflammasome in podocytes might be involved in the podocyte damage of ORG.
Animals ; Blotting, Western ; Body Weight ; physiology ; Inflammasomes ; metabolism ; Kidney Glomerulus ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein ; genetics ; metabolism ; Obesity ; complications ; Podocytes ; metabolism ; pathology ; Receptors, Purinergic P2X7 ; genetics ; metabolism

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

PURPOSE: Diabetic nephropathy is a serious complication of type 2 diabetes mellitus, and delaying the development of diabetic nephropathy in patients with diabetes mellitus is very important. In this study, we investigated inflammation, oxidative stress, and lipid metabolism to assess whether curcumin ameliorates diabetic nephropathy. MATERIALS AND METHODS: Animals were divided into three groups: Long-Evans-Tokushima-Otsuka rats for normal controls, Otsuka-Long-Evans-Tokushima Fatty (OLETF) rats for the diabetic group, and curcumin-treated (100 mg/kg/day) OLETF rats. We measured body and epididymal fat weights, and examined plasma glucose, adiponectin, and lipid profiles at 45 weeks. To confirm renal damage, we measured albumin-creatinine ratio, superoxide dismutase (SOD), and malondialdehyde (MDA) in urine samples. Glomerular basement membrane thickness and slit pore density were evaluated in the renal cortex tissue of rats. Furthermore, we conducted adenosine monophosphate-activated protein kinase (AMPK) signaling and oxidative stress-related nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling to investigate mechanisms of lipotoxicity in kidneys. RESULTS: Curcumin ameliorated albuminuria, pathophysiologic changes on the glomerulus, urinary MDA, and urinary SOD related with elevated Nrf2 signaling, as well as serum lipid-related index and ectopic lipid accumulation through activation of AMPK signaling. CONCLUSION: Collectively, these findings indicate that curcumin exerts renoprotective effects by inhibiting renal lipid accumulation and oxidative stress through AMPK and Nrf2 signaling pathway.
Albuminuria ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use ; Curcumin/*pharmacology ; Diabetes Mellitus, Type 2/*metabolism/urine ; Diabetic Nephropathies/complications/*drug therapy/metabolism/pathology ; Gene Expression/drug effects ; Inflammation ; Kidney/drug effects/metabolism/physiopathology ; Kidney Glomerulus/metabolism/physiopathology ; Lipid Metabolism/*drug effects ; Male ; Malondialdehyde/metabolism/urine ; Oxidative Stress/*drug effects ; Rats ; Rats, Inbred OLETF ; Rats, Long-Evans ; Superoxide Dismutase/metabolism

PURPOSE: Smoking reportedly exerts deleterious effects on renal function; however, its effects on histology have not been clarified in patients with IgA nephropathy (IgAN). MATERIALS AND METHODS: Renal histology was evaluated in a cohort of 397 patients diagnosed with IgAN according to smoking status and dose in relation to renal function. RESULTS: Among the study cohort, which was predominantly male (88.5%), 52 patients (13%) were current smokers. These current smokers demonstrated more frequent hypertension and higher serum creatinine levels than non/ex-smokers at the time of diagnosis, which was apparent with increased smoking dose. The percentages of global glomerulosclerosis and arteriolar hyalinosis increased with increased smoking dose, whereas tubulointerstitial fibrosis or arterial intimal thickening did not. Glomerular mesangial alpha-smooth muscle actin expression were similar between current and non/ex-smokers matched for age, gender, hypertension, and histologic severity, although the number of glomerular CD68+ cells was significantly fewer in smokers. Initial serum creatinine level, estimated glomerular filtration rate (eGFR), and global glomerulosclerosis were found to be risk factors of serum creatinine doubling in both smokers and non/ex-smokers by univariate analysis during a mean follow-up of 3.8 years. CONCLUSION: In addition to dose dependent renal functional decline and hypertension, smoking contributes to renal disease progression by eliciting microvascular injury in IgAN patients.
Adult ; Aged ; Case-Control Studies ; Cohort Studies ; Creatinine/blood ; Disease Progression ; Female ; Glomerulonephritis, IGA/blood/*diagnosis/epidemiology ; Humans ; Immunohistochemistry ; Kidney/*pathology ; Kidney Function Tests ; Kidney Glomerulus/*pathology ; Male ; Middle Aged ; Risk Factors ; Smoking/*adverse effects/epidemiology

OBJECTIVETo investigate the effect of Xuezhikang (, XZK) on renal cell apoptosis in diabetic rats and the possible mechanism.

METHODSSixty-six rats were randomly divided into 3 groups: the normal, model and XZK groups. In each group, the rats were further randomly divided into 3-month and 6-month subgroups, respectively. Diabetes of rats was induced by a single intraperitoneal injection of 1% streptozocin at 60 mg/kg body weight. Rats in the XZK group received gastric perfusion of XZK (1200 mg/kg body weight) everyday for 3 or 6 months, while rats in the normal and model groups received equal volume of saline. Twenty-four hours' urine was collected for urinary albumin excretion (UAE) measurement. Periodic acid-Schiff (PAS) and Masson's trichrome staining were used for saccharides and collagen detection. Cell apoptosis of renal cortex was investigated by TdT-mediated dUTP nick end labeling (TUNEL) staining. Bax and Bcl-2 expressions were detected by immunohistochemistry and Western blot, respectively. Cytochrome C (Cyt C) and caspase-9 concentration were detected by Western blot.

RESULTSCompared with the model group, XZK treatment could significantly decrease the kidney hypertrophy index, 24 h UAE, renal cell apoptosis, cytoplasmic Cyt C level and active caspase-9 level, as well as suppress the increment of Bax and up-regulate the expression of Bcl-2, leading to the suppression of Bax/Bcl-2 ratio at 3 and 6 months (P<0.05 or P<0.01). Moreover, XZK treatment could alleviate the deposition of PAS-stained saccharides and Masson's trichromestained collagen to different extent.

CONCLUSIONSRenal cell apoptosis was observed in diabetic kidney, in which mitochondrial apoptotic pathway might be involved. XZK treatment could attenuate pathological changes in diabetic kidney and reduce renal cell apoptosis, probably via the suppression of Bax/Bcl-2 ratio, which lead to inhibition of Cyt C release and following caspase-9 activation.

Albuminuria ; blood ; complications ; Animals ; Apoptosis ; drug effects ; Blood Glucose ; metabolism ; Caspase 9 ; metabolism ; Cytochromes c ; metabolism ; Diabetes Mellitus, Experimental ; blood ; drug therapy ; metabolism ; pathology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Hypertrophy ; In Situ Nick-End Labeling ; Kidney ; drug effects ; pathology ; Kidney Glomerulus ; pathology ; Lipids ; blood ; Male ; Mesangial Cells ; drug effects ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats, Sprague-Dawley ; Streptozocin ; bcl-2-Associated X Protein ; metabolism

OBJECTIVETo observe the effect of Wenyang Huoxue Lishui Recipe (WHLR) containing serum on the expression of cathepsin L (CatL) in puromycin aminonucleoside-induced injury of mouse glomerular podocytes.

METHODSMouse podocyte cells (MPCs) in vitro cultured were divided into the normal control group, the model group, the dexamethasone (DEX) group, 10% WHLR containing serum group, 20% WHLR containing serum group, the vehicle serum control group. MPCs in the normal control group were cultured at 37 degrees C culture solution for 24 h. 45 mg/L puromycin was acted on MPCs in the model group for 24 h. On the basis of puromycin intervention, 1 limol/L DEX was co-incubated in MPCs of the DEX group for 24 h; 10% or 20% WHLR containing serum was co-incubated in MPCs of the 10% WHLR containing serum group and 20% WHLR containing serum group for 24 h. The vehicle serum control group was also set up by incubating with WHLR containing serum alone for 24 h. The expression of CatL and its substrate Synaptopodin in podocytes were detected by cell immunofluorescence staining. FITC-conjugated phalloidin was used to stain F-actin. A cortical F-actin score index (CFS index) was designed to quantify the degree of cytoskeletal reorganization in cultured podocytes.

RESULTSCompared with the normal control group, the expression of synaptopodin significantly decreased and the expression of CatL significantly-increased in the model group. F-actin arranged in disorder, gradually forming pericellular F-actin ring. CFS index was obviously elevated (P < 0.01). Compared with the model group, the epression of synaptopodin increased, the expression of CatL decreased, and CFS index also decreased in the DEX group, 10% WHLR containing serum group, and 20% WHLR containing serum group (P < 0.05, P < 0.01). Compared with the DEX group, the expression of synaptopodin decreased in 10% WHLR containing serum group, CFS index also decreased in 20% WHLR containing serum group (P < 0.05).

CONCLUSIONSWHLR could up-regulate the expression of synaptopodin, down-regulate the expression of CatL, and alleviate cytoskeletal reorganization of F-actin. It was helpful to stabilize the cytoskeleton of F-actin and improve the merging of podocytes.

Actins ; metabolism ; Animals ; Cathepsin L ; metabolism ; Cells, Cultured ; Down-Regulation ; Drugs, Chinese Herbal ; pharmacology ; Kidney Glomerulus ; cytology ; Mice ; Microfilament Proteins ; metabolism ; Podocytes ; drug effects ; pathology ; Puromycin Aminonucleoside ; adverse effects ; Up-Regulation

There are several reports to demonstrate that rifampicin, a major anti-tuberculosis agent, is associated with some adverse renal effects, with a few cases of rifampicin-induced minimal change disease (MCD). In the present case, a 68-year-old female presented with nausea, vomiting, foamy urine, general weakness and edema. She had been taking rifampicin for 4 weeks due to pleural tuberculosis. The patient had no proteinuria before the anti-tuberculosis agents were started, but urine tests upon admission showed heavy proteinuria with a 24-h urinary protein of 9.2 g/day, and serum creatinine, albumin, and total cholesterol levels were 1.36 mg/dL, 2.40 g/dL, and 283 mg/dL, respectively. MCD was diagnosed, and the patient achieved complete remission after cessation of rifampicin without undergoing steroid therapy.
Aged ; Antibiotics, Antitubercular/*adverse effects/therapeutic use ; Edema/etiology ; Female ; Humans ; Kidney Function Tests ; Kidney Glomerulus/pathology ; Nausea/etiology ; Nephrosis, Lipoid/*chemically induced/pathology ; Proteinuria ; Remission Induction ; Rifampin/*adverse effects/therapeutic use ; Treatment Outcome ; Tuberculosis, Pleural/*drug therapy

OBJECTIVETo investigate the expression of BATF, a member of the activator protein-1 family, in the renal tissues of mice with lupus nephritis.

METHODSThe renal tissues from 24-week-old female MRL/lpr mice and age- and sex-matched C57BL/6 mice were examined for BATF protein expressions using Western blotting and for expressions of BATF, RORγt and IL-17A mRNA using quantitative real-time PCR. The results of laboratory examinations were analyzed in relation with the histopathology of the mice.

RESULTSThe urinary protein and ds-DNA levels were significantly higher in MRL/lpr mice than in the control mice (P<0.05). Compared to normal control mice, MRL/lpr mice showed obvious glomerular fibrosis and inflammatory cell infiltrating with significantly increased BATF protein and mRNA expressions (P<0.05) and RORγt and IL-17 mRNA expressions in the renal tissues (P<0.05). In MRL/lpr mice, the expression of BATF mRNA was positively correlated with the RORγt and IL-17A mRNA expressions in the renal tissues.

CONCLUSIONThe renal expressions of BATF protein and mRNA is increased in MRL/lpr mice. BATF may participate in the immunopathogenesis of lupus nephritis by enhancing Thl7 cell response.

Animals ; Basic-Leucine Zipper Transcription Factors ; metabolism ; Blotting, Western ; Female ; Interleukin-17 ; metabolism ; Kidney ; metabolism ; Kidney Glomerulus ; pathology ; Lupus Nephritis ; metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Inbred MRL lpr ; Nuclear Receptor Subfamily 1, Group F, Member 3 ; metabolism ; RNA, Messenger ; Real-Time Polymerase Chain Reaction

OBJECTIVETo investigate the prevalence of PLA2R1 in renal biopsy specimens of patients with idiopathic membranous nephropathy (IMN) and explore the relationship between PLA2R1 and IMN.

METHODSA total of 108 adult patients with biopsy-proved glomerular diseases were enrolled in this study, including 41 with IMN, 2 with hepatitis B-associated membranous nephropathy, 8 with V lupus nephritis, 27 with IgA nephropathy, 19 with minimal change nephropathy, 5 with mild mesangial proliferative glomerulonephritis, and 6 with focal segmental glomeruloselerosis (FSGS). Indirect immunofluorescence assay was used to detect PLA2R1 in the biopsy specimens and the clinical variables of the IMN patients were analyzed.

RESULTSIn 35 of the 41 (85.37%) patients with IMN, PLA2R1 was detected with a fine granular pattern in the subepithelial deposits along the glomerular capillary loops. PLA2R1 antigen was not detected in patients with other glomerulopathies. No significant differences were found in age, serum creatinine, serum albumin, or 24-h urinary protein level between PLA2R1-positive and negative patients with IMN (P>0.05).

CONCLUSIONAccording to our results, 85.37% of adult patients with biopsy-proven IMN are positive for PLA2R1 antigen, which, however, does not contribute to variations of the patients' clinical manifestations.

Adult ; Biopsy ; Glomerulonephritis, Membranous ; metabolism ; Humans ; Kidney ; metabolism ; pathology ; Kidney Function Tests ; Kidney Glomerulus ; pathology ; Nephrosis, Lipoid ; metabolism ; Receptors, Phospholipase A2 ; metabolism