Objective To study the prevalence and risk factors of chronic kidney disease (CKD) among adults in Zhengzhou. Methods One thousand eight hundred and fifty five residents (≥20 years) from 4 communities in 4 districts of Zhengzhou city were randomly selected by using a stratified，multistage sampling． They were interviewed, and received physical examination and measurements of urine and blood for renal damage as well as risk factors. Results Eligible data of 1752 subjects were included in the study． After the adjustment of age and gender component, albuminuria was found in 5.78％ of the subjects, hematuria in 8.19％, and reduced renal function in 1.58％. Male had lower prevalence of albuminuria and hematuria (4.37％ vs 7.29％, χ2=6.252, P=0.012; 5.08％ vs 11.51％, χ2=24.499, P＜0.01), but higher prevalence of reduced eGFR（2.26％ vs 0.86％, χ2=5.830, P=0.016) as compared with female. The prevalence of albuminuria and reduced eGFR increased with age. The crude prevalence of CKD was 14.50%, while the standardized rate was 13.57％. The prevalence of female was higher than that of male (17.83％ vs 9.59％, χ2=23.132, P＜0.01), which also increased with age. The most common manifestations of CKD were hematuria and albuminuria. Gender, age, smoking, hypertension, diabetes mellitus, obesity and hyperuricaemia were independently associated with CKD. The awareness rate of CKD was 8.27% and only 7.09% of the subjects received treatment. Conclusions The prevalence of CKD is 13.57％ and the recognition is 8.27％ in urban adult population of Zhengzhou．Independent risk factors associated with kidney damage are gender, age, smoking, hypertension, diabetes mellitus, obesity and hyperuricaemia．

Objective To investigate the prevalence and risk factors of adult chronic kidney disease (CKD) in the Xishuangbanna district of Yunnan province with a big population of minorities. Methods Residents aged 20 years and older in the area of Xishuangbannan were randomly selected by using a stratified, multi-stage sampling method. All the residents were tested for morning spot urine of albumin to creatinine ratio (ACR) (abnormal≥30 mg/g); morning spot urine dipstick of hematuria (abnormal l+ or greater) was confirmed by urine microscopy (abnormal >3 red blood cells/HP); and modified simplified MDRD equation for Chinese adult was applied to estimate GFR [abnormal <60 ml·min-1·(1.73 m2)-1]. The association among demographic characteristics, health characteristics (e.g. hyperglycemia, hyperlipidemia and hypertension) and indicators of kidney damage were also examined. Results Eligible data of 5566 subjects were included in the study. The prevalence of albuminuria was 8.06%, hematuria was 4.01% and reduced eGFR was 2.89%. Apart from the repetition among microalbuminuria, hematuria and reduced eGFR, approximately 12.53% subjects had at least one indicator of kidney damage. The prevalence of CKD in stratified subgroups with age, gender, nations and CKD risk factors was coincidence with the Logistic regression results. Age increase, hypertension, hyperlipidemia and fasting plasma glucose increase were independently associated with albuminuria; age increase, hypertension were independently associated with reduced renal function; age increase was independently associated with hematouria. Conclusions The prevalence of adult chronic kidney disease is 12.53% in the Xishuangbanna district of Yunnan province. Independent risk factors associated with kidney damage are age, hyperglycemia, hyperlipidemia and hypertension.

Objective To investigate the association of genetic polymorphisms in glutathione S-transferases T1 (GSTT1), M1 (GSTM1) and P1 (GSTP1) with aristolochic acid nephropathy (AAN) of Chinese people in Wenzhou of China. Methods Fifty-nine patients with AAN (AAN group) including 29 male and 30 female as well as 157 healthy ethnically matched controls (control group) including 93 male and 64 female were enrolled in this study. The genotypes of GSTT1, GSTM1 and GSTP1 were determined by multiple PCR and confronting two-pair primers PCR (CTPP-PCR). Results The genotype frequencies of GSTP1 were in Hardy-Weinberg equilibrium. Compared with the healthy controls, the frequency of GSTT1 null genotype was significantly higher in the patients with AAN (66.1％ vs 48.4％，P<0.05). Risk of AAN for individuals with GSTT1 null genotype was 1.747 fold of those without GSTTI null genotype (95% CI=0.818-3.731). The frequency of GSTM1 null genotype, GSTP1 variant genotypes and GSTP1 G allele in the patients and in the controls were 40.7％, 28.8％, 16.1％ and 47.8％, 31.8％, 17.5％, respectively, which were not significantly different. No significant differences were found in prevalence of GSTM1 and GSTP1 gene distribution between patients and controls. Conclusion GSTT1 gene polymorphism appears to be associated with susceptibility to AAN in Southern China.

Objective To investigate the mutations of podocyte molecules in patients with late onset familial focal segmental glomerular sclerosis (FSGS). Methods Thirty-one pedigrees of late onset familial FSGS in Department of Nephrology, Shanghai Ruijin Hospital from Sep 1997 to Oct 2007 were enrolled in this study. The diagnosis standard of familial FSGS was as follows：(1) the age of presentation was more than 12 years old. (2) in one pedigree, two or more individuals were proven as FSGS by renal biopsy, or at least one was proven to be FSGS by renal biopsy, the others presented renal insufficiency or proteinuria without precise causes. One hundred unrelated healthy people were screened as control group. Genomic DNA extracted from peripheral blood cells were amplified by PCR and then sequenced for mutations of NPHS2, ACTN4 and TRPC6. Results A novel missense heterozygotic mutation L316P of ACTN4 was identified in one pedigree. The mean onset age of the affected members of this pedigree was (38.7±7.4) years old and their kidney injury progress was slow. Proteinuria of the proband’s brother was not improved by immunosuppressor. All 3 affected members of this family had such heterozygotic mutation. A novel missense heterozygotic mutation Q889K of TRPC6 was found in another pedigree. The mean onset age of the affected members in this pedigree was (38.0±4.2) years old. Three members presenting renal disease in this family all had such heterozygotic mutation but with different clinical manifestations. A quiescent mutation G467G of TRPC6 was also identified. Above variants were not found in healthy controls. No NPHS2 mutation was found to cause familial FSGS in these pedigrees. Conclusions A novel mutation L316P of ACTN4 and a new mutation Q889K of TRPC6 are identified in Chinese patients of late onset familial FSGS. No NPHS2 mutation is found to induce FSGS in these pedigrees.

Objective To analyze the causes and clinical features of 20 patients with hemolytic uremic syndrome (HUS) in order to improve the prognosis. Methods Twenty patients with HUS hospitalized in our department during July 1998 to December 2004 were enrolled in this study. The etiology, clinical features, individualized therapy and prognosis were retrospectively analyzed. Results These 20 HUS patients(18 HUS patients complicated with ARF) accounted for 2.48% of total patients with acute renal failure (ARF) in our hospital. There were 16 females and 4 males with mean age of (49.11±19.85) years. Five patients were idiopathic HUS and the other 15 were secondary HUS (10 SLE-associated HUS, 2 pregnancy-associated HUS, 1 APS-associated HUS, 1 renal arterioles sclerosis-associated HUS and 1 drug-associated HUS). Eighteen cases had ARF and 15 had nephrotic syndrome. Hypertension was found in 17 patients, among them 4 had malignant hypertension. Twelve patients had gross hematuria and the other 8 had microscopic hematuria. Diarrhea was found only in 1 patient. At onset, mean serum creatinine was (504.40±381.10) μmol/L and 24-h proteinuria was (5.0±2.6) g. Renal biopsy was performed in 16 patients. Fourteen patients received hemopurification therapy: 2 patients plasma exchange (PE); 8 patients PE combined with CVVHDF and /or HD; 4 patients CVVHDF and HD. Seven cases were treated with intravenous immunoglobulin (IVIg). Patients with SLE-associated HUS received the corticosteroids and immunosuppressants. Low or middle dosage of corticosteroids（10-40 mg/d） was administered in patients with idiopathic HUS. For patients with APS, low molecular weight heparin was used. HUS patients were followed-up for average (46.0±32.8) months. During follow-up, 4 patients died, 11 recovered from renal insufficiency, 4 progressed to end stage renal failure of whom 2 depended on dialysis and 1 lost. The survival rates of SLE-associated HUS and none-SLE-associated HUS were 70% and 90%, and renal survival rates were 50% and 60% respectively, which were not significantly different between these two groups. Conclusions Most of the patients are secondary HUS. SLE-associated HUS is the main type of secondary HUS. The prognosis of SLE-associated HUS is poor. PE and IVIg are main therapy. Low dosage of corticosteroids can reduce relapse of HUS. Immunosuppressants can improve the prognosis.

Objective To investigate the change of aquaporin 2(AQP2) mRNA and protein levels in renal collecting duct of SD rats after hypoxia caused by rising of the altitude to 4600 m. Methods Forty male SD rats were randomly divided into 4 groups（24 h, 48 h, 72 h and 1 week group）, and 10 rats in Xining city were used as control group. All the 40 SD rats were transported to Kekexili Natural Reservation areas (4600 m) in Qinghai province. Rats of four experimental groups were sacrificed and renal tissue samples were harvested at different time point respectively, the control group rats were treated in Xining city(2260 m) as well. The concentration of plasma antidiuretic hormone (ADH) was measured by radioimmunity method. The expression of AQP2 mRNA and proteins was evaluated by real-time fluorescent quantitative-PCR, Western blot and immunofluorescence assay. Results The concentration of plasma ADH was decreased at 24 h and was only 28.5% of that of control group, reaching the lowest concentration at 48 h [(86.94±6.49) μg/L vs (302.53±10.48) μg/L], then it increased gradually and was similar to the control group at 7 d[（306.46±11.14) μg/L vs (302.53±10.48) μg/L, P＞ 0.05]. There were significant differences of the control group with 24 h, 48 h and 72 h groups, respectively[（302.53±10.48) μg/L vs (142.46±10.57) μg/L, (86.94±6.49) μg/L, (169.65±11.15) μg/L respectively, P<0.01]. The change of AQP2 gene expression level was consistent with the change of ADH. It was decreased at the begining when exposure to altitude and it reached its lowest level at 48 h. It was then returned to high level similarly to that of the control group at 7 d（0.09±0.01 vs 0.09±0.008, P＞0.05）. There were significant differences of the control group with 24 h, 48 h and 72 h group, respectively（0.09±0.008 vs 0.04±0.005, 0.03±0.002, 0.04±0.003 respectively, P<0.01）. Conclusions AQP2 expression in the renal collecting duct of SD rats is altered over the period exposed to altitude. It is decreased in the early hypoxia period, and is increased in later period. This change may be related to the intensity of hypoxia, which is mediated by a potential adaptation mechanisms against hypoxia caused by high altitude.

Objective To explore the protective effects of geranylgeranylacetone(GGA) on acute renal failure rats induced by ischemia reperfusion (IR) and the possible mechanism. Methods GGA (400 mg/kg) was administered to induce overexpression of heat shock protein 72 (HSP72) in the kidney of Sprague-Dawley (SD) rats. IR model was generated by temporary clamping the left renal artery for 45 minutes followed by right nephrectomy and 24 h reperfusion. A sham-operated group was used as normal control. 24 h after reperfusion, rats were sacrificed. Blood was collected for measurement of serum creatinine (Scr) and blood urea nitrogen ( BUN ). Paraffin-embedded sections of the kidney were stained with PAS. Histological changes due to tubular damage were quantitated as tubular damage score. TUNEL assay was used to detect the apoptosis, and Western-blot was used to detect the expression of XIAP. Results After renal IR, the increased level of BUN and Scr, the tubular injury and the apoptosis of renal tubular epithelial cells were observed (P<0.01). At the same time, the decreased level of XIAP was observed (P< 0.01). Compared with the control groups, the level of HSP72 expression was up-regulated in oral administration of GGA group (P<0.05). The expression levels of BUN and serum creatinine were significantly decreased after IR injury in pre-conditioned rats with over-expression of HSP72（P<0.01）. Kidney morphology was better preserved in GGA group. Rats with over-expression of HSP72 also revealed reduction of apoptotic cells by TUNEL stain and XIAP degradation by Western blot（P<0.05）. Conclusion GGA attenuates renal IR injury at least in part through inhibiting tubular cell apoptosis by decreasing XAIP degradation and restoring XIAP protein level.

Objective To elucidate whether AngⅡ indnces the proliferation of mesangial cells through ROS-EGFR-JNK-AP-1 signaling pathway. Methods The incorporation of 3H-thymidine (3H-TdR) and cell count were used to measure mesangial cell （MC） proliferation. ROS production was determined by DCFDA fluorescence. EGFR and JNK activation was assayed by Western blot. Results AngⅡ significantly enhanced ROS production in mesangial cells, which was up-regulated by 2.26 folds of control group after incubation with AngⅡ for 60 min. AngⅡ induced EGFR phosphorylation in dose- and time-dependent manner, with the peak (3.96 folds increase) at 30 min. EGFR phosphorylation was significantly blocked by AT1R antagonist losartan, antioxidant NAC, and NADPH oxidase inhibitor apocynin and DPI. EGFR antagonist AG1478 significantly inhibited AngⅡ-induced mesangial cell proliferation. Losartan, NAC, apocynin, DPI, and AG1478 almost abolished AngⅡ-induced JNK activation. Conclusions ROS-EGFR-JNK- AP-1 signaling pathway is involved in AngⅡ-induced mesangial cell proliferation. Apocynin and AG 1478 may be used as new therapy.

Objective To investigate the protective effects of fluvastatin(Flu) on rat renal fibroblasts proliferation and cytokines expression induced by cyclosporine A(CsA). Methods The fibroblasts were cultured with CsA or with CsA plus fluvastatin. The cellular proliferation was determined by MTT colorimetry. The mRNA expression of transforming growth factor β1(TGF-β1), connetive tissue growth factor (CTGF) and c-fos was detected by RT-RCR. The protein level of fibronectin (FN) was measured by Western blotting. Results CsA inhibited the proliferation of fibroblasts in dose- and time-dependent manner（P<0.05）. Treatment with Flu accelerated the suppression of fibroblasts resulted from CsA (P<0.01). CsA stimulated the expression of TGF-β1, CTGF, c-fos and FN compared with control group（P<0.05）, which could be down-regulated by Flu（P<0.05）. Conclusion Fluvastatin may relieve CsA-induced nephrotoxicity in rat fibroblasts.

Objective To investigate the influence of Cordyceps polysaccharide (Cp) on epithelial-to-mesenchymal transition (EMT) induced by transforming growth factor-β1（TGF-β1）in proximal tubular epithelial cells(PTEC). Methods HK-2 cell proliferation was determined by MTT assay. After incubation of HK2 cells with increasing concentrations of TGF-β1（0, 0.1, 0.5, 1, 5, 10 μg/L） at 48 h and with TGF-β1 （5 μg/L） at different time points, E-cadherin, α-SMA, FN expression at transcriptional and protein levels were detected by real-time PCR and Western blotting respectively. The cells were pretreated with 1, 5, 10 g/L Cp respectively for 24 h before adding TGF-β1（5 μg/L）, then the cells were incubated for additional 48 h, mRNA and protein expression of above 3 cytokines was examined by real-time PCR and Western blotting as well. Results CP alone (0.01, 0.1, 1, 5, 10 g/L) induced HK-2 cell proliferation in a dose-dependent manner. TGF-β1 enhanced α-SMA, FN expression while inhibited E-cadherin expression at both transcriptional and protein level in HK-2 cell. At transcriptional level, compared to single TGF-β1 (5 μg/L) stimulating group, after Cp (1, 5, 10 g/L) pretreatment for 24 h, the inhibition rate of α-SMA mRNA was 37.98%, 68.08% and 84.36%, respectively; FN mRNA was 46.97%, 63.82% and 81.85%, respectively; E-cadherin was up-regulated by 0.67 fold, 2.69 folds and 5.43 folds, respectively（P<0.05）. At protein level, the inhibition rate of α-SMA was 33.40%, 47.75% and 68.50%, respectively; FN was 16.26%, 65.92% and 80.30%, respectively; E-cadherin was up-regulated by 1.33 folds, 3.19 folds and 4.29 folds, respectively（all P<0.05). Under Light microscopy, the Cp reversed cell shape from spindle-shape induced by TGF-β1 to nearly normal shape. Conclusion Cp may exert its inhibitive effects on TGF-β1-induced EMT.

Objective To explore the influence of albumin-activated renal tubular epithelial cells （RTECs）on peritubular capillaries in co-culture system and its potential mechanism. Methods Endocytosis of TRITC labeled bovine serum albumin (TRITC-BSA) by HKC was detected by laser scanning confocal fluorescence microscope. HKC or HKC transfected with cubilin (endocytic receptor of albumin) siRNA or pre-treated with rotenone was incubated with albumin(20 g/L) for 24 h respectively. Fluorescence probe technique and spectrometry were applied for determination of intracellular superoxide anion O2－and H2O2 in supernatant. Then, the albumin-activated-HKC, pretreated-HKC with cubilin siRNA or rotenone, was cultured with HUVEC for 24 h in co-culture system respectively. HUVEC proliferation was determined by MTT and cellular apoptosis was analyzed by flow cytometry. Tubular morphogenesis of endothelial cells was examined by microscopy. Results TRITC-BSA uptake was obviously lower in HKC transfected with cubilin siRNA. Intracellular generation of O2－and H2O2 in culture supernatant was increased in dose- and time-dependent manner after stimulating with albumin. The levels of O2－ and H2O2 were suppressed by cubilin siRNA and rotenone. In co-culture system, albumin-activated-HKC induced endothelial cells apoptosis and inhibited their capillary tubular morphogenesis. Pretreatment of HKC with cubilin siRNA or rotenone could suppress endothelial cells apoptosis and promote capillary tubular morphogenesis. Conclusions There may be a crosstalk between RTECs and peritubular microvascular endothelial cells in renal proteinuric diseases. The generation of ROS by albumin-activated RTECs may play an important role in this process.

Objective To investigate the expression of angiotensinII (AngⅡ) and its type 1 receptor(AT1) in circulation, placenta and kidney of the rats preeclampsia. Methods Preeclampsia rat model was developed by inhibitor of nitric oxide synthase (L-NAME). The systolic blood pressure (SBP), 24 h urine protein, hepatic and renal function were compared among the preeclampsia group, the normal pregnant group and nonpregnant control group. The kidney tissue was observed by light microscopy. ELISA and radioimmunoassay were used to detect AngⅡ in rat plasma and kidney homogenate respectively. Placental AT1 was measured by Western blot. The level of kidney AT1 was evaluated by immunohistochemistry and Western blot. Results In preeclampsia rats, SBP and 24 h urine protein were significantly higher compared with control groups. Compared to normal pregnant group, plasma AngⅡ of preeclampsia rats was much higher[(0.706±0.086) ng/L vs (0.540±0.085) ng/L, P<0.05]; placental AT1 was increased by 46％（P<0.05）; kidney AngⅡ was decreased signigicantly [(65.543±40.634) ng/g vs (165.543±33.078) ng/g, P<0.05]. The expression of AT1 in kidney of preeclampsia rats was reduced evidently,which was only 33% of normal pregnancy group and 59% of nonpregnant control group,respectively (P<0.05). Conclusions In preeclampsia rat model, the circulating AngⅡ is increased, the placental RAS is activated, while the kidney RAS is suppressed. The underlying mechanism of proteinuria and kidney damage associated with this phenomenon in preeclampsia needs further research.