Shenkang injection (SKI) is a classic prescription composed of Radix Astragali, rhubarb, Astragalus, Safflower, and Salvia. This treatment was approved by the State Food and Drug Administration of China in 1999 for treatment of chronic kidney diseases based on good efficacy and safety. This study aimed to investigate the protective effect of SKI against high glucose (HG)-induced renal tubular cell senescence and its underlying mechanism. Primary renal proximal tubule epithelial cells were cultured in (1) control medium (control group), medium containing 5 mmol/L glucose; (2) mannitol medium (mannitol group), medium containing 5 mmol/L glucose, and 25 mmol/L mannitol; (3) HG medium (HG group) containing 30 mmol/L glucose; (4) SKI treatment at high (200 mg/L), medium (100 mg/L), or low (50 mg/L) concentration in HG medium (HG + SKI group); or (5) 200 mg/L SKI treatment in control medium (control + SKI group) for 72 h. HG-induced senescent cells showed the emergence of senescence associated heterochromatin foci, up-regulation of P16 and cyclin D1, increased senescence-associated β-galactosidase activity, and elevated expression of membrane decoy receptor 2. SKI treatment potently prevented these changes in a dose-independent manner. SKI treatment prevented HG-induced up-regulation of pro-senescence molecule mammalian target of rapamycin and p66Shc and down-regulation of anti-senescence molecules klotho, sirt1, and peroxisome proliferator-activated receptor-g in renal tubular epithelial cells. SKI may be a novel strategy for protecting against HG-induced renal tubular cell senescence in treatment of diabetic nephropathy.
Animals ; Cells, Cultured ; Cellular Senescence ; drug effects ; Cyclin D1 ; metabolism ; Cyclin-Dependent Kinase Inhibitor p16 ; metabolism ; Diabetic Nephropathies ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; Epithelial Cells ; drug effects ; metabolism ; Glucose ; Kidney Tubules, Proximal ; physiopathology ; Male ; Mice ; Mice, Inbred C57BL

OBJECTIVE: To investigate the effects of centella asiatica (CA) granule on the expression of transform growth factor-β(TGF-β) and related down-stream signals in rats with early diabetic nephropathy(DN) and to clarify the molecular mechanisms of CA molecular mechanism of on preventing and curing early diabetic kidney disease DN by studying the effects of centella asiatica on TGF-β expression and related down-stream signals. METHODS: Sixty male SD rats were divided into control group(=10) and DN model group(=50). The model rats were made a right nephrectomy. One week later, diabetic nephropathy was induced by intraperitoneal injection of streptocozin(30 mg/kg) for three consecutive days. High blood glucose level of Tail vein (fasting glucose ≥ 16.7 mmol/L) and high urinary protein level(total protein level in DN group was more than twice higher than the control group) were measured to confirm early DN in rats. In the sham operation group, the right renal capsule was damaged and the corresponding amount of saline was injected. The model rats were administrated by the means of intragastric administration. The DN model group were divided into DN group, DN+fosinopril group(1.6 mg/kg·d), DN+high CA group(16.8 mg/kg·d), DN+medium CA group(11.2 mg/kg·d) and DN+low CA group(5.6 mg/kg·d), and each group was intragastric administration one time every morning last for 16 weeks. The expressions of mRNA and protein of TGF-β, TβR1, TβR2, Smad2/3, Smad7 and the level of Smad2/3 phosphorylation were detected by using real time quantitative polymerase chain reaction and Western blot. RESULTS: The expressions of mRNA and protein of TGF-β, TβR1, TβR2, Smad2/3 and the level of Smad2/3 phosphorylation were significantly increased, the expressions of mRNA and protein of Smad7 were dramatically decreased. The fosinopril and high dosage CA could reverse the effects of DN. CONCLUSIONS CA plays an important role in preventing and curing DN through regulating the TGF-β/Smad signaling pathways.
Animals ; Centella ; chemistry ; Diabetes Mellitus, Experimental ; Diabetic Nephropathies ; chemically induced ; drug therapy ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Kidney ; physiopathology ; Male ; Rats ; Rats, Sprague-Dawley ; Receptor, Transforming Growth Factor-beta Type I ; metabolism ; Receptor, Transforming Growth Factor-beta Type II ; metabolism ; Signal Transduction ; Smad2 Protein ; metabolism ; Smad3 Protein ; metabolism ; Smad7 Protein ; metabolism ; Transforming Growth Factor beta1 ; metabolism

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

PURPOSE: Diabetes mellitus (DM) is the most common cause of end-stage renal disease (ESRD) and an important risk factor for cardiovascular (CV) disease. We investigated the impact of DM on subclinical CV damage by comprehensive screening protocol in ESRD patients. MATERIALS AND METHODS: Echocardiography, coronary computed tomography angiogram, 24-h ambulatory blood pressure monitoring, and central blood pressure with pulse wave velocity (PWV) were performed in 91 ESRD patients from the Cardiovascular and Metabolic disease Etiology Research Center-HIgh risk cohort. RESULTS: The DM group (n=38) had higher systolic blood pressure than the non-DM group (n=53), however, other clinical CV risk factors were not different between two groups. Central aortic systolic pressure (148.7±29.8 mm Hg vs. 133.7±27.0 mm Hg, p= 0.014), PWV (12.1±2.7 m/s vs. 9.4±2.1 m/s, p<0.001), and early mitral inflow to early mitral annulus velocity (16.7±6.4 vs. 13.7±5.9, p=0.026) were higher in the DM group. Although the prevalence of coronary artery disease (CAD) was not different between the DM and the non-DM group (95% vs. 84.4%, p=0.471), the severity of CAD was higher in the DM group (p=0.01). In multivariate regression analysis, DM was an independent determinant for central systolic pressure (p=0.011), PWV (p<0.001) and the prevalence of CAD (p=0.046). CONCLUSION: Diabetic ESRD patients have higher central systolic pressure and more advanced arteriosclerosis than the non-DM control group. These findings suggest that screening for subclinical CV damage may be helpful for diabetic ESRD patients.
Aged ; Aorta ; Biomarkers ; Blood Pressure/physiology ; Blood Pressure Monitoring, Ambulatory ; Coronary Artery Disease/diagnostic imaging/*physiopathology ; Diabetes Mellitus/*physiopathology ; Diabetic Nephropathies/physiopathology ; Echocardiography ; Female ; Humans ; Kidney Failure, Chronic/*physiopathology ; Male ; Middle Aged ; Pulse Wave Analysis ; Regression Analysis ; Risk Factors ; Systole/physiology

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

BACKGROUNDThe incidence of diabetic nephropathy (DN) increases year by year. However, clinical characteristics of DN patients on maintenance hemodialysis (MHD) were rarely reported in China. The purpose of this study was to examine the clinical characteristics of the DN patients on MHD in Anhui Province, Eastern China.

METHODSThe clinical data of MHD patients in the hemodialysis centers of 26 hospitals in Anhui Province from January 1, 2014, to March 31, 2014, were examined. The differences between DN patients and non-DN patients were compared regarding vascular access, nutritional status, mineral and bone disorder, and other indexes.

RESULTSAmong the selected 2768 adult MHD patients, 427 had DN. The incidence of hypertension, coronary heart disease, and cerebral thrombus in DN patients was 94.1%, 21.5%, and 15.0%, respectively, which were higher than those in non-DN patients (P < 0.001). Category of vascular access for hemodialysis in DN patients was arteriovenous fistula (AVF) (87.4% [373/427]) and tunneled cuffed catheter (TCC) (11.2% [48/427]). The percentage of AVF was significantly lower than that of non-DN patients (P < 0.001), and percentage of TCC was significantly higher than that of non-DN patients (P < 0.001). Hemoglobin achievement rate in DN patients was 32.0%. The incidence of hypoalbuminemia was 24.7%, significantly higher than that in non-DN patients (P < 0.001). The achievement rate of the target range in mineral values was 55.9% in corrected serum calcium level, 30.1% in serum phosphorus level, and 49.3% in intact parathyroid hormone (iPTH) level in DN patients. Compared with non-DN patients, the achievement rate of serum phosphorus was significantly higher in DN patients.

CONCLUSIONSDN patients on MHD in Anhui province exhibited different clinical characteristics compared to non-DN hemodialysis patients. They presented higher percentage in TCC use and cardiovascular complication, lower serum albumin and iPTH levels than those in non-DN patients.

Aged ; Calcium ; blood ; China ; Coronary Disease ; blood ; epidemiology ; physiopathology ; Cross-Sectional Studies ; Diabetic Nephropathies ; blood ; epidemiology ; physiopathology ; Female ; Humans ; Hypertension ; blood ; epidemiology ; physiopathology ; Intracranial Thrombosis ; blood ; epidemiology ; physiopathology ; Male ; Middle Aged ; Parathyroid Hormone ; blood ; Phosphorus ; blood ; Renal Dialysis

OBJECTIVE: To explore the correlation between diabetic nephropathy (DN) and cognitive impairment through examining the cognitive function and the metabolism of the cerebrum in Type 2 diabetes mellitus patients at different stages of renal function.
 METHODS: Eighty six patients with Type 2 diabetes mellitus (T2DM) were enrolled for this study. According to the urinary albumin excretion rate (UAER), the patients were divided into a T2DM without DN group (DM group, n=33), an early DN group (DN-III group, n=26) and a clinical stage group (DN-IV group, n=27). Thirty healthy adults were selected as a control group (NC group). Biochemical indexes and UAER were measured, and glomerular filtration rate (GFR) was detected by single-photon emission computed tomography (SPECT). The cognitive function was measured by Montreal Cognitive Assessment (MoCA, Beijing version) and mini-mental state examination (MMSE). The peak areas of N-acetylasparte (NAA), creatine (Cr), choline-containing compounds (Cho) were detected by proton magnetic resonance spectroscopy (1H-MRS).
 RESULTS: 1) There was no statistical difference in MMSE scores between the DM group and the control group. The scores of MoCA in the DN-III group or in the DN-IV group were significant less than that in the NC group (F=3.66, P<0.05); 2) There was significant difference in left N-acetylaspartate (LNAA), left choline (LCho) among the diabetes groups. Compared with the DM group, the level of LNAA was decreased significantly (t=3.826, P<0.05) while the LCho was increased significantly (t=4.373, P<0.05) in the DN groups, with statistic difference between the 2 groups (t=3.693, P<0.05); 3) The MoCA scores of T2DM patients were negatively correlated with UAER (r=-0.285, P<0.05), while positively correlated with GFR (r=0.379, P<0.05); 4) Logistic regression analysis indicated that UAER and GFR were the major risky factors for diabetic cognitive impairment.
 CONCLUSION Diabetic cognitive impairment is closely correlated with the nephropathy in patients with Type 2 diabetes. With the decline in glomerular filtration function, the cognitive disorder tends to be aggravated. The hippocampal brain metabolism may have some changes in left side of Cho/Cr in patients with diabetic nephropathy.
Adult ; Aspartic Acid ; analogs & derivatives ; metabolism ; Case-Control Studies ; Cerebrum ; metabolism ; Choline ; metabolism ; Cognition ; Cognition Disorders ; epidemiology ; Creatine ; metabolism ; Diabetes Mellitus, Type 2 ; physiopathology ; Diabetic Nephropathies ; epidemiology ; Glomerular Filtration Rate ; Humans ; Neuropsychological Tests

OBJECTIVETo examine the renal function changes and mechanisms on rats with diabetes through a sleeve gastrectomy operation.

METHODSThirty-six rats were induced diabetes through injection of streptozotocin (STZ), and 30 of these diabetic rats that blood glucose levels at the midrange (blood sugar 17.88-23.65 mmol/L, mean: 20.32 mmol/L) were randomly assigned to the sleeve gastrectomy group, Sham-operation group and control group. The serum creatinine, lipid parameters were measured postoperatively. The 24 h urine volume obtained and urine albumin excretion rate (UAER) was calculated. Serum and urinary creatinine were examined and glomerular filtration rate (GFR) was counted. Kidney sections were stained with periodic acid-Schiff, and then the index of mesangial expansion was determined. The expression of synaptopodin for podocytes was also performed through the immunohistochemical procedure. A one-way ANOVA and t-test were performed to evaluate differences between groups and each other.

RESULTSOnly one rat of SG group died after operation. The GFR ((8.44 ± 2.10) ml · g⁻¹ · d⁻¹), 24 h UAER ((36.04 ± 11.10) mg/d), plasma lipids level (total cholesterol (1.66 ± 0.23) mmol/L, triglycerides (1.25 ± 0.17) mmol/L), kidney weight ((1.61 ± 0.06) g), the index of mesangial expansion ((6.14 ± 1.50)%) and synaptopodin expression ((20.44 ± 2.99)%) were improved in the SG group compared with the sham-operation group ((15.05 ± 3.01) ml · g⁻¹ · d⁻¹, (57.01 ± 11.34) mg/d, (2.15 ± 0.29) mmol/L, (1.65 ± 0.23) mmol/L, (1.93 ± 0.07) g, (11.32 ± 2.09)%, (10.34 ± 1.43)%) and control group ((14.79 ± 2.38) ml · g⁻¹ · d⁻¹, (62.71 ± 16.46) mg/d, (2.23 ± 0.21) mmol/L, (1.59 ± 0.20) mmol/L, (1.91 ± 0.06) g, (10.82 ± 1.79)%, (11.13 ± 2.43)%) (t = 0.781-5.025, all P < 0.05).

CONCLUSIONThe sleeve gastrectomy procedure can improve the renal function in a diabetes rat model may be through protecting the podocytes function and preventing the mesangial expansion of glomeruli.

Animals ; Blood Glucose ; Creatinine ; blood ; urine ; Diabetes Mellitus, Experimental ; physiopathology ; Diabetic Nephropathies ; physiopathology ; surgery ; Gastrectomy ; Glomerular Filtration Rate ; Kidney ; physiopathology ; Kidney Function Tests ; Random Allocation ; Rats

Arteriovenous Shunt, Surgical ; adverse effects ; Brachial Artery ; diagnostic imaging ; Diabetic Nephropathies ; complications ; therapy ; Hematoma ; complications ; diagnostic imaging ; Humans ; Magnetic Resonance Imaging ; Male ; Median Neuropathy ; diagnostic imaging ; etiology ; physiopathology ; Middle Aged ; Neural Conduction ; Renal Dialysis ; Ultrasonography

BACKGROUND/AIMS: Diabetic cystopathy is a frequent complication of diabetes mellitus. This study assessed the association between the post-voiding residual (PVR) urine volume and diabetic nephropathy in type 2 diabetics with no voiding symptoms. METHODS: This study investigated 42 patients with type 2 diabetes who were followed regularly at our outpatient clinic between July 1, 2008 and June 30, 2009. No patient had voiding problems or International Prostate Symptom Scores (IPSSs) > or = 12. An urologist performed the urological evaluations and the PVR was measured using a bladder scan. A PVR > 50 mL on two consecutive voids was considered abnormal, which was the primary study outcome. RESULTS: The mean patient age was 60 +/- 10 years; the IPSS score was 3.7 +/- 3.3; and the diabetes duration was 11.9 +/- 7.8 years. Seven of the 42 patients (16.7%) had a PVR > 50 mL. The presence of overt proteinuria or microalbuminuria was associated with an increased risk of a PVR > 50 mL (p < 0.01). Patients with a PVR > 50 mL had a significantly lower estimated glomerular filtration rate (eGFR) compared with those with a PVR < or = 50 mL (59.2 +/- 27.1 mL/min/1.73 m2 vs. 28.7 +/- 23.3 mL/min/1.73 m2; p < 0.001). Multivariate logistic analysis revealed that a lower eGFR (odds ratio, 0.94; 95% confidence interval, 0.88 to 0.99; p = 0.04) was a significant risk factor for a PVR > 50 mL. CONCLUSIONS: Patients with diabetic nephropathy had a significantly higher PVR and a lower eGFR was associated with an abnormal PVR.
Adult ; Aged ; Aged, 80 and over ; Diabetes Mellitus, Type 2/*complications/diagnosis ; Diabetic Nephropathies/diagnosis/*etiology/physiopathology ; Female ; *Glomerular Filtration Rate ; Humans ; Kidney/*physiopathology ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Outpatient Clinics, Hospital ; Republic of Korea ; Risk Factors ; Time Factors ; *Urodynamics