Advances on pathogenesis of acquired peritoneal ultrafiltration failure in peritoneal dialysis / 中华肾脏病杂志

Peritoneal ultrafiltration failure is a common reason for peritoneal dialysis (PD) withdrawal as well as mortality in PD patients. Based on the three-pore system, inter-cellular small pores and trans-cellular ultra-small pores (aquaporin-1) are mainly responsible for water transfer across the peritoneum. Both small and ultra-small pores-dependent water (free water) transport decline accompanied with time on PD, with more significant decrease in free water, resulting in peritoneal ultrafiltration failure. The reduction of free water transport is associated with fast peritoneal solute transfer, reduced crystalloid osmotic gradient due to increased interstitial glucose absorption, and declined osmotic conductance to glucose resulted from impaired aquaporin-1 function and peritoneal interstitial fibrosis. The decline of small pore-based water is mainly because of fast loss of crystalloid osmotic gradient, decrease of hydrostatic pressure mediated by peritoneal vasculopathy, as well as reduced absolute number of small pores. The current review discusses the advance on pathogenesis of acquired peritoneal ultrafiltration failure in long-term PD.

IgA nephropathy standard dataset and quality control / 中华肾脏病杂志

Objective:To establish a IgA nephropathy (IgAN) standard dataset for the structured and standardization of IgAN clinical information, which will be beneficial to the integration and utilization of clinical information among different medical institutions. Therefore, the IgAN Expert Collaboration Group composed the "IgA Nephropathy Standard Dataset".Methods:Referring to the domestic information standards, guidelines, data standard and consensus of related fields, based on electronic medical history, the patient identification number was used as the primary key of the system to collect information. By standardizing each data element in the data set, the standardization of the management system in data and information exchange, data collaboration and sharing was ensured, and a quality control system was developed.Results:This standard dataset included 607 data elements and 8 business domains, which were patient information, medical history information, physical examination, laboratory examination, assistant examination, renal pathology, drug treatment, and follow-up, respectively. Each module was composed of module name, data element name, English name, definition, range, reference standard, etc. At the same time, a corresponding quality control system was formulated to evaluate data quality from multiple dimensions such as completeness, standardization, accuracy, timeliness, and security for ensuring the high quality and security of the data.Conclusion:The IgAN standard dataset is established, which will contribute to the structuration and standardization of clinical information of IgAN patients.

Culture and identification of parietal epithelial cells of Bowman′s capsule / 中华肾脏病杂志

Objective:To explore the isolation and culture methods of mouse parietal epithelial cells (PECs) of Bowman′s capsule, so as to provide a cell tool for further study.Methods:Mouse renal corpuscles were isolated by cell sieving combined with magnetic separation. After primary culture, identified parietal epithelial cells were induced to differentiate into podocytes. Immunofluorescence staining, real-time quantitative PCR and Western blotting were used to detect specific markers of parietal epithelial cells and podocytes.Results:Primary cultured PECs grew like paving stone and expressed Claudin-1 (PECs specific marker), CD133 (stem cell marker) and CD24 (stem cell marker), without the expression of tubular epithelial cell proteins, mesangial cell and podocyte specific proteins. Cultured to 6 generations in vitro, the PECs still expressed Claudin-1, CD133 and CD24. After incubated with differentiation medium, PECs were able to express podocyte markers WT-1 and Synaptopodin. Conclusion:The renal corpuscles are extracted by cell sieving combined with magnetic separation, and the mouse PECs successfully cultured in vitro can be induced to express podocytes′ markers.

Incidence of cognitive impairment and risk factors associated with prognosis in maintenance hemodialysis patients / 中华肾脏病杂志

Objective@#To investigate the incidence and prognosis of cognitive impairment and to find out the risk factors associated with the outcome for better understanding and preventing cognitive impairment in maintenance hemodialysis (MHD) patients.@*Methods@#The patients who met the criteria as below: MHD patients (≥3 months) in Renji Hospital, Shanghai Jiao Tong University School of Medicine from January 2000 to July 2014, ≥18 years old were enrolled and could carry on the montreal cognitive assessment (MoCA) of voluntary cooperation. According to the score of MoCA, all enrolled patients were divided into two groups: cognitive impairment (MoCA<26) group and non-cognitive impairment (MoCA≥26) group. The follow-up period was 3 years. There were 130 males, and the incidence, demography data, medical history, hemodialysis data, laboratory examination and prognosis of cognitive impairment in hemodialysis patients were prospectively compared and analyzed. Logistic regression analysis was used to investigate the risk factors of cognitive impairment. Kaplan-Meier survival curve and Cox regression model were used for prognostic analysis.@*Results@#A total of 219 MHD patients were enrolled. The incidence of cognitive impairment in MHD patients was 51.6%. There were 130 males, and the ratio of male to female was 1.46∶1. Age was (60.07±12.44) years old and dialysis vintage was (100.79±70.23) months. Compared with non-cognitive impairment group (n=106), patients in cognitive impairment group (n=113) were older, and had higher proportion of education status<12 years, history of diabetes and anuria (all P<0.05); however, the post-dialysis systolic pressure, pre-dialysis diastolic pressure, post-dialysis diastolic pressure, platelet and spKt/V were lower (all P<0.05). Multivariate logistic regression analysis showed that education status<12 years (OR=3.428, 95%CI 1.919-6.125, P<0.001), post-dialysis diastolic pressure<73 mmHg (OR=2.234, 95%CI 1.253-3.984, P=0.006) and spKt/V<1.72(OR=1.982, 95%CI 1.102-3.564, P=0.022) were the independent risk factors for cognitive impairment in MHD patients. The Kaplan-Meier survival curve analysis showed that the survival rate of patients with cognitive impairment was lower than that of non-cognitive impairment group in MHD patients during 3 years follow-up (χ2=3.977, P=0.046). Multivariate Cox regression analysis showed that cognitive impairment was an independent risk factor for death in MHD patients (RR=2.661, 95%CI 0.967-7.321, P=0.058).@*Conclusions@#Cognitive impairment is one of the common complications and an independent risk factor for death in MHD patients. The mortality is high in patients who suffer cognitive impairment. Education status<12 years, post-dialysis diastolic pressure<73 mmHg and spKt/V<1.72 are the independent risk factors for cognitive impairment in MHD patients.

Incidence of cognitive impairment and risk factors associated with prognosis in maintenance hemodialysis patients / 中华肾脏病杂志

Objective To investigate the incidence and prognosis of cognitive impairment and to find out the risk factors associated with the outcome for better understanding and preventing cognitive impairment in maintenance hemodialysis (MHD) patients. Methods The patients who met the criteria as below: MHD patients (≥3 months) in Renji Hospital, Shanghai Jiao Tong University School of Medicine from January 2000 to July 2014, ≥18 years old were enrolled and could carry on the montreal cognitive assessment (MoCA) of voluntary cooperation. According to the score of MoCA, all enrolled patients were divided into two groups: cognitive impairment (MoCA<26) group and non-cognitive impairment (MoCA≥26) group. The follow-up period was 3 years. There were 130 males, and the incidence, demography data, medical history, hemodialysis data, laboratory examination and prognosis of cognitive impairment in hemodialysis patients were prospectively compared and analyzed. Logistic regression analysis was used to investigate the risk factors of cognitive impairment. Kaplan-Meier survival curve and Cox regression model were used for prognostic analysis. Results A total of 219 MHD patients were enrolled. The incidence of cognitive impairment in MHD patients was 51.6％. There were 130 males, and the ratio of male to female was 1.46:1. Age was (60.07 ± 12.44) years old and dialysis vintage was (100.79 ± 70.23) months. Compared with non-cognitive impairment group (n=106), patients in cognitive impairment group (n=113) were older, and had higher proportion of education status<12 years, history of diabetes and anuria (all P<0.05); however, the post-dialysis systolic pressure, pre-dialysis diastolic pressure, post-dialysis diastolic pressure, platelet and spKt/V were lower (all P<0.05). Multivariate logistic regression analysis showed that education status<12 years (OR=3.428, 95％CI 1.919-6.125, P<0.001), post-dialysis diastolic pressure<73 mmHg (OR=2.234, 95％CI 1.253-3.984, P=0.006) and spKt/V<1.72(OR=1.982, 95％CI 1.102-3.564, P=0.022) were the independent risk factors for cognitive impairment in MHD patients. The Kaplan-Meier survival curve analysis showed that the survival rate of patients with cognitive impairment was lower than that of non-cognitive impairment group in MHD patients during 3 years follow-up (χ2=3.977, P=0.046). Multivariate Cox regression analysis showed that cognitive impairment was an independent risk factor for death in MHD patients (RR=2.661, 95％CI 0.967-7.321, P=0.058). Conclusions Cognitive impairment is one of the common complications and an independent risk factor for death in MHD patients. The mortality is high in patients who suffer cognitive impairment. Education status<12 years, post-dialysis diastolic pressure<73 mmHg and spKt/V<1.72 are the independent risk factors for cognitive impairment in MHD patients.

Predictors of response in patients with progressive IgA nephropathy treated with leflunomide and medium/low-dose corticosteroid / 中华肾脏病杂志

Objective To investigate the factors affecting the efficacy of leflunomide combined with medium/low dose corticosteroids in the treatment of progressive IgA nephropathy (IgAN).Methods Clinical and pathological parameters were collected retrospectively in patients of primary IgAN with proteinuria＞ 1.0 g/24 h and chronic kidney disease (CKD) stage 1-3 treated with leflunomide combined with medium/low dose corticosteroids in Ren Ji Hospital,School of Medicine,Shanghai Jiao Tong University from Jan 2005 to Dec 2010.According to the treatment effects,patients were divided into complete remission group and non-complete remission group.The biochemical and pathological indexes of the two groups were compared.Results A total of 42 patients were included.The remission rates at 3,6,9 and 12 months were 62％,64％,67％ and 74％,respectively.Seventeen (40.5％) and fourteen (33.3％) patients achieved complete and partial remission after one-year treatment,and the remission rate remained stable within one year after withdrawal of drugs.The 24hour proteinuria was 1.50 (0.67,2.66) g,which was significantly reduced compared with the baseline 2.44 (1.36,3.74) g (P ＜ 0.01).The decrease rate was 31.3％.There was a slight decrease in proteinuriawithin one year after withdrawal of drugs.Estimated glomerular filtration rate (eGFR) remained stable during the treatment and a year of follow-up.No serious adverse event was observed during the followup period.Among 31 responder patients,6(19.4％) patients relapsed.Logistic multivariate regression analysis suggested that the degree of renal interstitial inflammatory infiltration was an independent predictor of complete remission with one-year treatment of leflunomide combined with medium / low dose corticosteroids (HR=0.067,95％ CI 0.008-0.535,P=0.011).Conclusions IgAN treated with leflunomide and medium/low dose corticosteroids can achieve remission in early stage,and the remission rate remains stable after withdrawal of drugs.It is a safe option for the treatment of IgAN.Renal interstitial inflammatory infiltration is an independent predictor of complete remission.

Contrast induces kidney epithelial cell apoptosis through NRLP3 inflammasome pathway / 中华肾脏病杂志

Objective To investigate the effect of pyrin domain 3 (NLRP3) inflammasome in the process of contrast induced human kidney cell apoptosis.Methods Human kidney 2 (HK-2) cells were cultured in DMEM-F12 medium with 5％ FBS.Cells were divided into control group,Contrast group (O group),NLRP3-siRNA+Iohexol group (si-NLRP3+O group),ASC-siRNA+Iohexol group (si-ASC+O group),and mannitol group (M group).Different concentrations of hypotonic contrast agent were added to HK-2 cell culture plates for 24,48 and 72 h.Flow cytometry was used to detect apoptosis.NLRP3 and ASC mRNA expressions were detected by RT-PCR.The expressions of NLRP3,ASC,caspase-8/cleaved caspase-8,Bcl-2/Bax,caspase-1/cleaved caspase-1,and caspase-3/cleaved caspase-3 protein were detected by Western blot.The levels of interleukin (IL) 1β and IL-18 in supernatant were detected by ELISA.Results Compared with the control group,the rate of apoptotic cells,as well as the expressions of NLRP3,ASC and cleaved caspase-1 proteins were increased in HK-2 cells of contrast group.The expressions of NLRP3 and ASC mRNA in the contrast group also increased,so did IL-1β and IL-18 levels (all P＜0.05),suggesting that NLRP3 inflammasome in HK-2 cells was activated by contrast.Compared with the control group,the expressions of cleaved caspase-8,Bax and cleaved caspase-3 protein were increased,and the expression of anti-apoptotic protein Bcl-2 was decreased (all P ＜ 0.05).Compared with the contrast group,the rate of apoptotic cells in the si-NLRP3 + contrast group and si-ASC + contrast group was significantly decreased;the expression of cleaved caspase-1 was decreased;the expressions of Bax and cleaved caspase-3 were decreased,and Bcl-2 level was increased.The expressions of IL-1β and IL-18 in the supernatant of cells were decreased (all P ＜ 0.05).Conclusion Contrast agent can activate the NLRP3 pathway in HK-2 cells and induce apoptosis,which could be reduced by blocking the NLRP3 pathway.

Effect of activating PKA signaling on dedifferentiation of podocytes in adriamycin-induced nephropathy mice / 上海交通大学学报（医学版）

Objective·To explore effects of pCPT-cAMP on proteinuria and dedifferentiation of podocytes in adriamycin (ADR)-induced nephropathy mice. Methods·Male BALB/c mice were divided into three groups. The control group did not make any intervention, and the other mice were administrated with ADR in a dose of 10 mg/kg by intravenous injection (ADR group). Some ADR-injected mice were treated with pCPT-cAMP [50 mg/(kg·d)] by intraperitoneal injection everyday (A+P group). Albumin urine was detected by Coomassie blue stain. Urine creatinine concentration was estimated by ELISA. The expression of WT-1 was detected by immunohistochemical staining. Immunofluorescence staining and Western blotting were used to evulate the dedifferentiation of podocytes. Results·Compared with the control group, the ratio of urinary albumin/creatinine in ADR nephropathy mice was significantly increased. WT-1 immunohistochemical staining showed that the number of podocytes was significantly decreased, while immunofluorescence double staining of podocyte-specific protein synaptopodin and podocalyxin remarkably reduced, and the expression of desmin was increased. pCPT-cAMP intervention decreased the ratio of albumin/creatinine in ADR mice, elevated the quantity of WT-1 positive cells and the expression of synaptopodin and podocalyxin, while desmin expression decreased. Conclusion·pCPT-cAMP activates the PKA signaling and protects ADR nephropathy mice by preventing the loss of podocytes and ameliorating the urine albumin/creatinine ratio, which may be mediated by pCPT-cAMP-prevented dedifferentiation of podocytes.

Renji acute kidney injury score is a useful tool to predict acute kidney injury after cardiac surgery / 中华肾脏病杂志

Objective To validate the effect of Renji acute kidney injury score (RAKIS) on predicting patients with acute kidney injury (AKI) after cardiac surgeries,and make comparison with Cleveland score,simplified renal index (SRI) and acute kidney injury following cardiac surgery (AKICS).Methods Patients undergoing open heart surgery from 2008/01/01 to 2010/10/31 in Renji hospital were enrolled,and their scores of those four scoring models were calculated.AKI patients were diagnosed by KDIGO,and those scores of AKI patients and non-AKI patients were compared.Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to decide the predictive values of those models.Results A total of 1126 patients were chosen in this cohort,with the average age of (58.43±14.88) years (rang from 18 to 88).The male to female ratio was 1.47:1.And 355(31.5％) patients were developed AKI.AKI stage Ⅰ,Ⅱ and Ⅲ were 65.4％,23.7％ and 11.0％ respectively.RAKIS was significantly higher in AKI patients than in non-AKI patients (17.5 vs 9.0,P ＜ 0.001).The AUCs of RAKIS to predict AKI,AKI Ⅱ-Ⅲ stages,renal replacement therapy (RRT)and in-hospital death were 0.818,0.819,0.800 and 0.784 respectively.The AUCs of Cleveland score and SRI were 0.659 to 0.710,lower than those of RAKIS and AKICS.AKICS had lower value for predicting AKI and AKI Ⅱ-Ⅲ stages (AUC 0.766 and 0.793),but good value in predicting RRT and inhospital death after surgery (AUC 0.804 and 0.835) as compared with RAKIS.Conclusions RAKIS is valid and accurate in the discrimination of KDIGO defined AKI patients,while for predicting the composite end point,AKICS may be more useful.

Leflunomide combined with medium/low dose corticosteroids vs full dose of corticosteroids in treatment of IgA nephropathy / 中华肾脏病杂志

Objective To compare the efficacy and safety of leflunomide (LEF) combined with medium/low dose corticosteroids and full dose of corticosteroids in the treatment of IgA nephropathy. Method Primary IgAN patients diagnosed by renal biopsy with 18?65 years old and eGFR≥30 ml·min?1·(1.73 m2)?1 and proteinuria>0.5 g/24 h were enrolled in a prospective controlled clinical study. They were randomly divided into leflunomide combined with medium/low dose corticosteroids (LEF group) and corticosteroids alone (steroid group). The primary outcomes were (1) end stage renal disease or dialysis (2) 50% increase in serum creatinine above the baseline. Secondary outcome was the remission of proteinuria. Results Ninety patients completed the follow?up. The 24?hour proteinuria at baseline were 2.00(1.10, 2.88) g and 1.87(1.13 ,3.08) g in LEF group and steroid group respectively. Compared with baseline, it was significantly decreased in both groups at 6 months [0.30(0.11, 0.93) g, 0.30(0.14, 1.33) g] and 12 months [0.30(0.09, 0.82) g, 0.32(0.14, 0.66) g], (P0.05]. At 6 and 12 months, there was no significant difference in terms of 24?hour proteinuria, serum creatinine and eGFR (CKD?EPI) between groups (P>0.05). There was no statistically significant difference in adverse events between groups during the treatment (9/40 cases in LEF group and 11/50 cases in steroid group, P>0.05). The average follow?up was 79 months, and there was no difference in the renal prognosis between the two groups. Multivariate Cox regression analysis revealed that serum creatinine at baseline and renal interstitial inflammatory cell infiltration predicted the risk of the progress of IgA nephropathy. Conclusion Leflunomide plus medium/low dose corticosteroids has a similar effect as full dose of corticosteroids in IgA nephropathy and does not increase the risk for adverse events during the treatment.

Initial study on the incidence of colorectal diseases in 719 patients with chronic kidney disease / 中华消化杂志

Objective To investigate the incidence of colorectal disease in patients with chronic kidney disease (CKD) and analyze the risk factor of colorectal disease in patients with CKD.Methods The clinical data of 719 patients with CKD underwent colonoscopy examination and 404 patients without CKD underwent colonoscopy examination were collected.The incidence of colorectal disease was compared between patients of the two groups.According to the results of colonoscopy examination,the patients with CKD were divided into colonoscopy positive group and negative group,and clinical biochemical indexes of the two groups were analyzed.The rank-sum test or t-test was used to compare the measurement data.Rates were compared by Chi-square test.The risk factors of colorectal disease in patients with CKD were evaluated by logistic regression.Results The positive rate of colonoscopy examination in 719 patients with CKD was 21.28％ (153/719),which was higher than that of patients without CKD (12.62 ％,51/404; x2 =13.036,P＜0.01).The positive rate of colonoscopy in patients with CKD at stage 1 was 17.50％ (56/320),at stage 2 or 3 was 22.68％(66/291),at stage 4 or 5 was 28.70％ (31/108).There were significant differences among the three groups (x2-6.623,P＜0.05).The incidence of colorectal cancer in patients with CKD was 3.89 ％ (28/719),which was higher than that of patients without CKD (1.73％,7/404; x2 =4.003,P＜0.05).The incidence of colorectal polyps in CKD group was 8.34％(60/719),which was higher than that of non-CKD group (5.20％,21/404; x2 =3.827,P＜0.05).The incidence of inflammatory bowel disease in CKD group was 9.04％(65/719),which was higher than that of non-CKD group (5.69 ％,23/404; x2 =4.013,P＜0.05).The incidence of colorectal cancer and colorectal polyps in patients with CKD at stage Ⅰ was 2.50％(8/320) and 6.25％(20/320),at stage 2 or 3 was 3.78％(11/291) and 8.59％(25/291),at stage 4 or 5 was 8.33％(9/108) and 13.89％ (15/108).There were significant differences among the three groups (x2-7.359 and 6.199,both P＜ 0.05).The age of colonoscopy positive group was older than that of colonoscopy negative group (t=-3.821,P＜0.01); there were lower hemoglobin (t=3.541,P＜0.01),increased erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) (Z=-4.996 and-7.493,both P＜0.01),higher cholesterol and low density lipoprotein (t=-2.659 and-3.248,both P＜0.01),increased serum creatinine (Z=-3.683,P＜0.01) and declined glomerular filtration rate (Z=-6.227,P＜0.01) in colonoscopy positive group than in colonoscopy negative group; the differences were statistically significant.Logistic regression analysis indicated that age (β=0.981,95％ CI 0.965 to 0.998,P =0.032),serum creatinine (β=1.006,95％CI 1.002 to 1.009,P=0.001) and ESR (β=1.029,95％CI 1.018 to 1.040,P＜0.01) were risk factors of colorectal disease in patients with CKD.Conclusions The incidence of colorectal disease in patients with CKD is high,and it increases along with the declined glomerular filtration rate.The colorectal disease in patients with CKD patients may be associated with age,anemia,lipid metabolism,inflammation and impaired renal function.

Resveratrol activates Notch signalling pathway via Sirtuin 1 in podocytes / 中华肾脏病杂志

Objective To explore the relationship between resveratrol and Notch 1 signalling pathway in podocytes.Methods Interference RNA (RNAi) and doxycycline (Dox) were used to inhibit the Sirtuin (SIRT) 1 expression in the wild-type and inducible SIRT1 shRNA (CAGGS) podocytes respectively.Recombinant mouse delta-like ligand 4 (DLL4) was used to activate Notch1 signalling.The message RNA of SIRT1,Notch1 downstream gene Hes1 and Hey2,as well as the key enzymes of Notch1 signalling pathway were detected by using real-time PCR.Western blotting was used to detect intracellular domain of Notch 1 (ICD1),SIRT1,and metalloprotease (ADAM) 10 and components of γ-secretase complex protein expression.Results In WT murine podoytes,resveratrol up-regulated ICD1 protein production,as well as the mRNA of Hes1 and Hey2 in a dose-dependent manner.Treatment with resveratrol resulted Nicastrin mRNA and protein increase in podocytes (P ＜0.05),as well as inhibit ADAM10 expression (P ＜ 0.05),but all these changes were prevented after the use of SIRT1 RNAi(P ＜ 0.05).DLL4 up-regulated the expression of mRNA of Hes1 and Hey2,as well as ICD1 protein production in a dose-dependent manner.Treatment with doxycycline resulted decrease of SIRT1 gene and protein expression in CAGGS podocytes after 24 h and 48 h respectively(P ＜ 0.05),which weakend the role of DLL4 significantly(P ＜ 0.05).Conclusion Resveratrol induces Nicastrin expression,as well as activation of Notch1 signalling pathway in a SIRT1-dependent manner.

cAMP/PKA signal activation prevents chemical-induced podocyte injury / 中华肾脏病杂志

Objective To investigate the role of activated cylic AMP(cAMP) signaling in chemical-induced podocyte injury.Methods Eight-weeks-old male BalB/C mice were randomly divided into three groups:control group,Adriamycin (ADR) group and Forskolin+ADR group.ADR nephropathy models were established by tail intravenous injection,and part of them were injected Forskolin,an agonist of adenylate cyclase,intraperitoneally.Phosphorylation of cAMP response element binding protein (CREB) was detected by laser confocal microscopy,morphology of foot processes were determined with transmission electron microscope,and WT-1 expression in glomeruli were detected by immunohistochemistry.Conditionally immortalized podocytes were treated with puromycin aminonucleoside (PAN),Exchange protein directly activated by cAMP (Epac) agonist 8-pCPT-2-O-Me-cAMP (2Me),protein kinase A (PKA) antagonist H89 and its agonist pCPT-cAMP(pCPT).Western blot was used to detect the expression levels of Epac,caspase3 and cleaved caspase3.PKA activity was assayed using cAMP-dependent protein kinase detection system.Cell viability was determined by a cell count kit and podocyte apoptosis was estimated by TUNEL staining.Mitochondrial membrane potential was evaluated by JC-1 staining.Results (1)Compared with ADR group,the urine albumin decreased significantly (P ＜ 0.05) among Forskolin + ADR group and the WT-1 positive cells per glomerulus increased obviously (P ＜ 0.05).(2)PAN decreased podocyte number in a time-dependent manner (P ＜ 0.05),pre-treatment with pCPT obviously inhibited PAN induced podocyte decrease (P ＜0.05),but H89 prevented the effect of pCPT in a dose-dependent manner (P ＜ 0.05).(3)JC-1 staining showed that the percentage of podocyte with green fluorescence for control,PAN and pCPT+PAN group were (12.67±2.15)％,(31.35±4.60)％ and (16.96 ± 2.51)％ respectively (P ＜ 0.05),and pretreatment with H89 inhibited the effect of pCPT (P ＜ 0.05).(4) PAN promoted podocyte apoptosis and cleaved caspase3 expression (P ＜ 0.05),and pretreatment with pCPT significantly prevented PAN-induced podocyte apoptosis and cleaved caspase3 expression (P ＜ 0.05).Conclusions cAMP signaling activation ameliorated podocyte injury in ADR nice and PAN-induced podocyte apoptosis,and cAMP/ PKA pathway may mediate these processes.

Analysis of clinical characteristics of twice-weekly hemodialysis patients / 中华肾脏病杂志

Objective To investigate the clinical characteristics of twice-weekly hemodialysis patients.Methods Data were collected from Shanghai Renal Registry.A total of 1288 patients undergoing regular hemodialysis (HD) with dialysis adequacy index and other biochemical parameters in Shanghai in January 2007 were enrolled into the cohort study with 2 years follow-up.Clinical characteristics and outcome of twice-weekly HD patients were analyzed as compared with thrice-weekly HD patients.Results Compared with patients on thrice-weekly HD,the twice-weekly HD patients were significantly younger and had significantly shorter HD vintage,smaller body surface area,longer HD session time,higher single-pool Kt/V (spKt/V) and serum albumin but lower weekly Kt/V (P＜0.05).There was no statistical difference in ultrafiltration volume between two groups.Kaplan-Meier survival analysis indicated that both groups had similar two-year survival.Multivariate Cox regression analysis showed that age,body mass index,serum albumin and weekly Kt/V were predictors of patient mortality.Conclusion It is acceptable for some hemodialys patients with twice-weekly HD,and close monitor of dialysis adequacy and volume status is necessary for this therapy model.

Immunofecal occult blood test predicts the prognosis of patients with chronic kidney disease / 中华肾脏病杂志

Objective To evaluate the value of immunofecal occult blood test (IFOBT) as a prognostic indicator in CKD patients with colorectal impairment.Methods A total of 176CKD patients and 180 healthy adults as control were enrolled.Serum biochemistry was measured at baseline and gastrointestinal bleeding was determined by IFOBT.All the CKD patients were followed up for 4.5 years.Renal replacement therapy or death was defined as end-point event.The Logistic regression analysis was used for risk factors.Kaplan-Meier analysis and COX regression model were used for survival analysis.Results The positive rate of IFOBT in CKD patients was significantly higher than healthy control (17％ vs 5.3％,χ2=13.236,P＜0.01).When comparing with IFOBT negitive patients,IFOBT positive patients were older [(62.030±15.544) years old vs (48.660±19.018)years old,P＜0.01],had higher ESR [(71.800±31.657) mu/h vs (57.210±32.712) mm/h,P＜0.05],C-reactive protein [6.230 (3.000～14.148) mg/L vs 3.000 (3.000～6.833)mg/L,P＜0.05],serum creatinine [419.100 (103.200～546.625) μmol/L vs 175.100 (68.150～462.950) μmol/L,P＜0.05],and had lower hemoglobin level [(97.970±20.590) g/L vs (107.170±27.988) g/L,P＜0.05] and eGFR [11.400 (8.671～53.544) ml·min1·(1.73 m2)1 vs 35.274(10.961～82.145) ml·min-1·(1.73 m2)-1,P＜0.01].There was a negative correlation between IFOBT value and eGFR in CKD patients (r=-0.20,P＜0.01).Positive correlations of IFOBT value with age (r=0.175,P＜0.05) and serum creatinine (r=0.171,P＜0.05) were found.Logistic regression and COX regression analysis showed that IFOBT value,eGFR and ESR were important factors that influenced the prognosis of CKD patients.Kaplan-Meier analysis revealed that IFOBT value ＞100μg/L predicted progression of renal function.Conclusions The prevalence of gastrointestinal bleeding disorder is high in patients with CKD.Value of IFOBT independently predicts decline in renal function of CKD patients.

Functional metabotropic glutamate receptor 1 and 5 expression in podocytes / 中华肾脏病杂志

Objective To investigate the expression of metabotropic glutamate receptor (mGluR) in murine podocytes.Methods Conditional immortalized podocytes were used in the research.RT-PCR was used to estimate the mRNA expression.Western blotting,immunofluorescence staining and immunoelectron microscopy were employed to determine the protein production.EIA,EMSA and Western blotting were used to examine the cAMP generation and cAMP response element-binding protein (CREB) activation.Intracellular calcium was investigated using confocal microscopy.Results mGluR1 and 5 mRNA and protein were expressed in murine brain and podocytes.In glomeruli,most of mGluR1 expression located in podocytes and was expressed in the submembrane space of the podocytes.Podocytes treated with (S)-3,5-dihydroxyphenylglycine (DHPG,an agonist for mGluR1/5) rapidly generated cAMP and activated CREB.(RS)-1-Aminoindan-1,5-dicarboxylic acid (AIDA,a selective antagonist of mGluR1/5) and SQ22536 (an adenylate cyclase inhibitor),but not 2-aminoethoxydiphenyl borate (2-APB an antagonist of canonical transient receptor potential) blocked DHPG-induced cAMP generation and CREB activation.Following DHPG treatment,intracellular calcium level rose and was prevented by pre-treatment with AIDA and 2-APB.DHPG-induced calcium influx was also prevented by incubation with calcium-free medium.Conclusion Podocytes express functional mGluR1 and mGluR5.

Incidence of acute kidney injury according to AKI Network after cardiac surgery and analysis of risk factors and outcome / 中华肾脏病杂志

Objective To investigate the incidence, risk factors and outcome of acute kidney injury (AKI) following cardiac surgeries. Methods Clinical data of 1056 patients undergoing open heart surgery in Renji Hospital from January 2004 to June 2007 were retrospectively analyzed. Univariate and multivariate analyses were used to evaluate possible pre-,intra-, and post-operative parameters associated with AKI according to AKI Network (AKIN). Results Of the 1056 patients, 328 (31.06%) developed AKI. In-hospital mortality was 4.07% in all discharges while 11.59% in AKI patients (P<0.01). Multivariate logistic regression analysis revealed that increased age (OR=1.40), pre-operative hyperurieemia (OR=1.97), pre-operative left ventricular insufficiency (OR=2.53), combined surgery (OR=2.79), prolonged operation time (OR=1.43), post-operative circulation volume insufficiency (OR=11.08) were risk factors of AKI. Conclusions AKI is a common complication and associated with increased mortality following cardiac surgery. Increased age, pre-operative hyperuricemia, pre-operative left ventricular insufficiency, combined surgery, prolonged operation time, post-operative circulation volume insufficiency are useful in stratifying risk factors for the development of AKI.

Effect of high glucose on the expression of liver X receptors and ABCA1 in human THP-1 macrophages / 中华肾脏病杂志

Objective To investigate the effect of high glucose on the expression of liver X receptors (LXRs) and ATP-binding cassette transporter A1 (ABCA1) in human macrophages (THP-1 cell line). Methods THP-1 monocytes were differentiated into macrophages by induction of phorbol 12, 13-dibutyrate (PMA). Surface markers of macrophages were identified by CD68 immunohistochemistry. The macrophages were cultured with different concentration (5.6, 11.1, 22.2 and 33.3 mmol/L) of glucose and different time (0, 0.5, 2, 6, 12, 24, 48, 72 h). Real time PCR and Western blotting methods were used to examine the mRNA and protein expression of LXRs and ABCA1. Results As compared to 5.6 mmol/L glucose, macrophage LXRβ and ABCA1 were decreased significantly at both mRNA and protein levels in dose-and time-dependent manner (P<0.05). Conclusion Hyperglycemia may play a role in the pathogenesis of arteriosclerosis through the inhibition of LXRs and ABCA1 expression in diabetic patients.

Association between non-dipping circadian blood pressure rhythm and left ventricular hypertrophy in chronic kidney disease patients / 中华肾脏病杂志

Objective To clarify the association between non-dipping circadian blood pressure (BP) rhythm and left ventrieular hypertrophy (LVH) in chronic kidney disease (CKD) patients. Methods A total of 257 CKD patients of stage 1 to 5 were enrolled in the study. The parameters of BP and circadian rhythm were measured by ambulatory BP monitoring (ABPM) and the cardiac structure was examined by echocardiography. The association between circadian BP rhythm and echocardiographic parameters was studied. Results The prevalence of abnormal circadian BP rhythm (non-dipping rhythm) was quite high (75.4%) in CKD patients and increased with the deterioration of renal function. Even if in the normal BP group, the prevalence of non-dipping rhythm was 71.3%. The change of cardiac structure such as LVH in non-dipping patients was more obvious than the dipping patients. The left ventrieular mass index (LVMI) was positively correlated with BP, non-dipping rhythm. Multiple regression analysis showed that 24 h-SBP (β=0.417, P<0.01), triglyceride (TG) (β=-0.132, P=O.007), Hb (β=-0.394, P=0.016) and gender(β=0.158, P=0.039) were independent risk factors of LVMI. Conclusions The prevalence of non-dipping rhythm is quite high in CKD patients and increases with the deterioration of renal function. The change of cardiac structure such as LVH is obvious in CKD patients, especially in non-dipping group. The non-dipping rhythm is related with LVMI.

Implication of plasma pentraxin 3 in peripheral arterial disease of hemodialysis patients / 中华肾脏病杂志

Objective To clarify the role of pentraxin 3 (PTX3) in the development of peripheral arterial disease (PAD) in maintenance hemodialysis (MHD) patients. Methods One hundred and sixteen patients undergone MHD therapy in our center for more than 3 months were enrolled in the study. Clinical data were collected for analysis. Ankle-brachial index (ABI) was used to estimate the presence of PAD. Patients were divided into PAD group (ABI<0.9) and nonestimate the association of PAD with PTX3 as well as other potential risk factors. Results The incidence of PAD was 18.1% (21/116). Plasma level of PTX3 was significantly higher in PAD patients than that in non-PAD patients [(5.55 ±2.63) μg/L vs (2.32 ±1.29)μg/L, P<0.01].Univariate analysis showed ABI values were negatively correlated with plasma PTX3 levels (r =-0.548, P<0.01), high-sensitivity C-reactive protein (hsCRP), age, blood glucose and triglyceride. ROC curve of PAD revealed that area under curve (AUC) of PTX3 was 0.901 (P<0.01). With the cut-off value of PTX3 as 4.06 μg/L, the diagnostic sensitivity and specificity in PAD were 81.0% and 91.5%. ROC curve of PAD showed that AUC of hsCRP was 0.640 (P<0.05). With the cut-off value of hsCRP as 3.33 mg/L, the diagnostic sensitivity and specificity in PAD were 57.1% and 56.8%. Using Logistic regression, plasma PTX3 was found to be associated with PAD (0R=9.755, 95%CI:2.359-19.354, P=0.001). Conclusions The PAD incidence of MHD patients in our center is 18.1%. Plasma PTX3 level is significantly correlated with the presence of PAD in MHD patients. The sensitivity and specificity of PTX3 are higher than those of hsCRP for PAD diagnosis.