Objective To conduct a population-based screening program in Guangzhou urban area and to identify the prevalence of chronic kidney disease（CKD） and risk factors in the general adult population of southern China. Methods 2213 residents （older than 20 years） from 3 communities in 2 districts of Guangzhou city were randomly selected using a stratified, multi-stage sampling. All residents were interviewed and tested for morning spot urine of albumin to creatinine ratio (ACR) ( abnormal: ≥30 mg/g ); morning spot urine dipstick of hematuria (abnormal: 1+ or greater) confirmed by urine microscopy (abnormal: >3 red blood cells /HP); and MDRD equation estimated GFR[abnormal: <60 ml·min^-1·(1.73 m²)^-1]. The associations of kidney damage indicators with age, gender, smoking, diabetes mellitus, hypertension and hyperuricemia were examined. Results Eligible data of 2128 subjects were enrolled in the study. After the adjustment of age and gender component, the prevalence of albuminuria was 6.16% （95% CI:5.9%~6.42%）, hematuria 6.5%（95%CI：5.3%~7.8%）, and reduced eGFR 1.64%（95%CI:1.3%~1.98%）. Approximately 10.1% subjects had at least one indicator of kidney damage. Age, diabetes mellitus and hypertension were independently associated with CKD. Conclusions The prevalence of chronic kidney disease is 10.1% and the recognition is 9.7% in urban adult population of southern China. Independent risk factors associated with kidney damage are age, diabetes mellitus and hypertension.

Objective To investigate the prevalence of chronic kidney disease(CKD) and associated factors in a village of Zhejiang province. Methods All residents older than 18 years in the village were interviewed and screened for albuminuria with morning spot urine albumin to creatinine ratio (abnormal:≥30 mg/g), reduced renal function with estimated glomerular filtration rate by modified MDRD equation [abnomal: <60 ml·min^-1·（173 m²)^-1; hematuria with morning spot urine dipstick confirmed by urine sediments microscopy test. The correlations among demographic characteristics, health characteristics (eg. smoking, diabetes and hypertension) and indicators of kidney damage were examined. Results Complete information was obtained in 76.2% of the residents. After age and gender adjustment, the prevalence of albuminuria, reduced renal function and hematuria was 10.4%, 3.0% and 1.4%, respectively. Compared with subjects older than 40 years in Beijing and NHANES Ⅲ, participants older than 40 years in the present study tended to have lower prevalence of diabetes and hypertension, and higher prevalence of albuminuria and reduced renal function. Age and diabetes and systolic blood pressure were independently correlated with albuminuria. Female, age and hyperuricemia were independently correlated with reduced renal function. Age and smoking were independently correlated with reduced renal function. Conclusion The spectrum and correlated factors of CKD in a village undergoing rapidly economic development are close to those of Beijing and developed countries, while certain specific factors might contribute to the high prevalence of CKD in the present village.

Objective To evaluate the efficiency and safety of carvedilol (Dilatrend^®) in refractory hypertensive patients with different kidney diseases. Methods A multi-centre, prospective，opening, self-compared trial was conducted. Two hundred and seventeen patients were enrolled in this study. Before and after 8-week treatment, blood pressure, heart rate, plasma norepinephrine and serum creatinine etc. were measured and recorded. Results Mean blood pressure at 4th week significantly reduced in comparison with that before the use of carvedilol (P < 0.05). Total and dominant efficiency were 57.1% and 11.5% at 4th week, 79.7% and 26.7% at 8th week. Mean heart rate declined from 79.3±10.2 per minute to 75.9±7.6 per minute at 4th week, and 75.0±8.5 per minute at 8th week (P< 0.05). Mean plasma norepinephrine level decreased from 38.7 ng/L before trial to 17.6 ng/L (P < 0.05). Adverse events usually appeared mild, and no obvious changes of biochemical parameters of liver and renal function and electrocardiogram were found. Conclusion Carvedilol is an efficient and safe antihypertensive drug in treatment of different kidney diseases.

Objective To clarify the association of BNP with atherosclerotic cardiovascular disease(CVD) and cardiac dysfunction in predialysis patients with chronic kidney disease(CKD). Methods Whole blood concentration of BNP was detected by fluorescence immunoassay in a cohort of 203 non-dialysis CKD patients and 16 hypertensive controls. The relationship of BNP with carotid artery atherosclerosis evaluated by B-ultrasound, echocardiographic parameter and history of cardiovascular disease in CKD patients was examined. Results BNP level was significantly higher in CKD patients than that in control subjects [54.40(15.10~173.00) ng/L vs 9.35(7.35~15.00) ng/L, P<0.01]. Spearman correlation showed that the BNP level was positively correlated with carotid intima-media thickness (IMT) and left ventricle mass index (LVMI). BNP concentration was significantly higher in patients with carotid plaques, left ventricular hypertrophy (LVH) and cardiovascular disease (CVD) history. Multiple regression analysis revealed that LVMI and CVD history were independent determinants of BNP. Conclusions BNP level is significantly correlated with atherosclerotic cardiovescular disease, LVH and cardiac dysfunction. BNP may be a sensitive biomarker for the evaluation of atherosclerosis and cardiac function in non-dialysis CKD patients.

Objective To investigate the influence of coronary artery calcification (CAC) on cardiac changes and its correlative factors in maintenance hemodialysis patients (MHD). Methods A retrospective study was performed on 40 patients. Quantification of CAC was determined by multislice spiral CT scan. Cardiac function and cardiac geometry were evaluated by two-dimensional, Doppler ultrasonography. Carotid atherosclerosis was measured by high resolution B-mode ultrasound. The relationship of clinical data and CAC was analyzed. Results The mean calcification score was 672.3, and 25 patients (62.5%) had CAC. Compared with CAC, cardiac geometry, left ventricular compliance, carotid intima-media thickness (IMT), presence of carotid plaque, and plaque score were significantly different in none CAC. Ischemic heart disease and episodes of cardiac failure appeared more frequently in CAC patients. Four patients died from cardiac disease, and each of them had CAC. Carotid IMT, presence of carotid plaque and plaque score were higher in plaque-positive groups than those in plaque-negative patients [0.86±0.15 mm, 81%,867±198 vs (0.73±0.14) mm, 42%,437±176,P < 0.05]. Patients with CAC were older, more commonly diabetic and obesity, and showed higher levels of serum phosphorus, Ca×P product, CRP， total and LDL cholesterol, carotid IMT, plaque score and longer duration of hemodialysis, as compared to patients without CAC. Multiple regression analysis showed that CAC was independently influenced by age and duration of hemodialysis. Conclusions CAC is commonly found in MHD patients. Echocardiography demonstrates that CAC is associated with cardiac structure, function and carotid atherosclerosis. The correlative factors of CAC includes the proportion of diabetes and obesity, levels of serum phosphorus, Ca×P product, total and LDL cholesterol, duration of hemodialysis, CRP，artherosclerosis. Age and duration of hemodialysis are the independent risk factors of CAC.

Objective To evaluate the effects of telmisartan on expression of integrin α3 and integrin-linked kinase (ILK) in 20-month-old Sprague-Dawley rats by intraperitoneal injection of streptozotocin （STZ）. Methods STZ rats were treated with or without telmisartan for up to 12 weeks. 24-hour albuminuria, blood pressure and urinary podocytes were measured at weeks 4, 8 and 12，respectively. Animals were sacrificed at week 12. Serum and urinary creatinine were measured and kidney tissues were harvested. Expression of integrin α3 and ILK mRNA and protein in glomeruli was evaluated by RT-PCR, immunohistochemistry and Western-blot, respectively. Results STZ aging rats presented significant podocyte damage, albuminuria and excretion of urinary podocyte. Telmisartan reduced urinary podocytes and protected STZ aging rats from renal damage. Integrin α3 expression in STZ aging rat was markedly decreased (P < 0.05), while expression of ILK was significantly increased. The level of ILK expression was negatively correlated with integrin α3 expression（r＝-0.64, P < 0.05）and positively with urinary podocyte and albuminuria after 12 weeks (r＝0.79 and 0.74, P < 0.05 respectively). Telmisartan obviously extenuated STZ-associated reduction in integrin α3 and increasement in ILK (P < 0.05). Conclusion The alterations in integrin α3 and ILK expression as well as the modulating effect of telmisartan are directly involved in the pathogenesis of podocyte injury.

Objective To investigate the regulatory mechanism of mitogen-activated protein kinase (MAPK ) in Cyr61 trans-activation induced by hypoxia in HKC cells. Methods The expression levels of Cyr61, p38, ERK1/2, JNK, and HIF-1α in HKC cells induced by hypoxia were analyzed by Nothern and Western blot. Full length of Cyr61 promoter region was amplified by PCR and recombinant plasmid of Cyr-luc were constructed. After transfection alone or coexpression with vector overexpressing constitutively active forms of either MEK1 (Ca-MEK1), or MKK6 (Ca-MKK6) , the trans-activation of Cyr61 in HKC cells induced by hypoxia, MAPK pathway inhibitors or MAPK kinase were assayed by means of luciferase reporter gene assay system. Results Cyr61 and HIF-1α were expressed at an obviously high level in HKC cells cultured under hypoxia. The phosphorylation content of ERK, JNK,p38 in the HKC cells increased along with the time of hypoxia, while there were no significant differences in total ERK, JNK and p38 expression. The luciferase activity was inhibited separately by PD98059 or SB203580 in HKC cells transfected with Cyr-luc plasmid,and it was obviously enhanced by the cotreated with PD98059 and SB203580. The trans-activation of Cyr61 in HKC cells transfected with Cyr-luc was not affected after cotransfected with Ca-MEK1,but was significantly increased with Ca-MKK6. The protein expression of Cyr61 and HIF-1α was inhibited by PD98059 in HKC cells under hypoxia, and the same effect of SB203580 on Cyr61 was seen as well. The inhibition of Cyr61 protein expression was significantly improved when cotreated by PD98059 and SB203580. Conclusion　 In HKC cells, hypoxia stimulates the trans-activation of Cyr61 through p38 MAPK pathway directly , and also adjusts HIF-1α expression through ERK1/2 pathway,which could stimulates the trans-activation of Cyr61 indirectly.

Objective To observe the influence of epigallocatechin-3-gallate (EGCG) on extracellular signal-regulated kinase in diabetics rats. Methods Diabetes mellitus was induced in male Sprague-Dawley (SD) rats (150~200 mg) by intraperitoneal injection of streptozotocin (65 mg/kg). Blood glucose levels were measured three days after the injection to ensure a diabetic state (≥16.7 mmol/L). Then diabetic rats were randomly assigned to one of the following groups: (1) diabetic model (DM). (2) diabetic+EGCG treatment (with intraperitoneal EGCG injections 7 days after diabetic model establishment). In addition, the normal control group was injected with intraperitoneal citric acid. The treatment continued for 12 weeks, and then the rats were sacrificed and the kidneys were harvested for immunohistochemistry staining of p-ERK to evaluate the protein expression level. The rat mesangial cells were divided into six groups: normal glucose (NG, 5 mmol/L) control group, high glucose (HG, 30 mmol/L) control group, HG＋EGCG 1 (100 μg/L), HG＋EGCG 2 (200 μg/L), HG＋EGCG 4 (400 μg/L), and mannitol group. The expression of ERK, p-ERK and p27 protein was examined by Western blot. Results Compared with control group, there was significant increase in p-ERK staining area in the glomeruli of untreated diabetic rats. EGCG treatment significantly suppressed the increased p-ERK staining area. Compared with normal glucose group, high glucose significantly increased the expression of p-ERK and p27 protein. EGCG could decrease the expression of p-ERK and p27 protein. Conclusions EGCG can inhibit p-ERK protein expression in kidneys of diabetic rats and rat mesangial cells cultured in high glucose. EGCG may be used to prevent or cure diabetic nephropathy.

Objective To investigate the effects of losartan on renal inflammation reaction and podocyte injury in the kidney of diabetic rat. Methods Wistar rats were randomly divided into normal control group (NC), diabetes group（DM）, and losartan treated group(DL)（20 mg·kg^-1·d^-1 by gavages）. Diabetes was induced by intraperitoneal injection of streptozotocin （STZ）. After administration of losartan for 2 weeks and 12 weeks, 24-hour urinary protein excretion (24 hUPE), Scr and Ccr were measured, and renal morphology was observed. The expression levels of ICAM-1, CD45, nephrin and VEGF were examined by immunohistochemistry and Western blot. Results Compared with DM, kidney weight （KW）, KW/body weight（KW/BW）, 24 hUPE and Ccr in DL were significantly decreased（P < 0.05，or P < 0.01）. The expression levels of ICAM-1, CD45 and VEGF in DM and DL group were higher than those in NC group. Losartan inhibited the increased levels of ICAM-1,CD45 and VEGF as well as decreased levels of nephrin in DL. The levels of ICAM-1, CD45, VEGF, nephrin and blood glucose were correlated with the excretion of urine protein. There was a positive correlation between ICAM-1 and VEGF (r = 0.756, P < 0.01), as well as CD45 and VEGF (r =0.774, P < 0.01). There was a negative correlation between ICAM-1 and nephrin (r =-0.589, P < 0.05), as well as CD45 and nephrin (r = -0.664, P < 0.01). Conclusion Renoprotection of losartan on diabetic rats may be mediated through, at least partly, suppressing the increase of renal inflammatory stress and attenuating podocyte injury.

Objective To observe the effect of TGF-β1 on the pro-inflammatory cytokine expression induced by lipopolysaccharide(LPS) in rat peritoneal mesothelial cells(RPMCs), and explore its possible mechanism. Methods RPMCs were isolated from rat peritoneum. The RPMCs were incubated with LPS (1 mg/L), TGF-β1(5 μg/L), or stimulated by LPS (1 mg/L) after incubated with TGF-β1 (5 μg/L) for 1 h. RPMCs of control group were just incubated with medium. TNF-α and IL-6 mRNA were detected by RT-PCR. Their protein levels were examined by ELISA. NF-κB protein was detected by Western blot. Results Compared with control group, the expression of pro-inflammatory cytokine (TNF-α, IL-6) was significantly increased in the groups stimulated by LPS and TGF-β1. Also, the NF-κB was activated by LPS and TGF-β1. In the group pre-incubated by TGF-β1 for 1 hour, up-regulating expression of TNF-α mRNA and protein was significantly inhibited. Furthermore, NF-κB activation was also partly inhibited by pre-treatment with TGF-β1. Conclusion TGF-β1 may inhibit pro-inflammatory cytokine expression induced by lipopolysaccharide in rat peritoneal mesothelial cells through the inactivation of NF-κB signal transduction pathway.