Objective To study the impact and mechanism of continuous venovenous hemofiltration (CVVH) in different uhrafihration rates on plasma cytokines in porcine endotoxemic shock. Methods Eighteen anesthetized mechanically ventilated pigs weighing 21-34 kg were randomly divided into three groups. In control group (n=6), the pigs received a 15.7 μg/kg endotoxin (E.coli 0111:84) infusion. In CVVH group (n=6) and high volume hemofihration (HVHF) group (n=6), the pigs received CVVH after the endotoxin infusion for 24 hours with an was taken before endotoxin infusion and at 0, 1, 6, 12, 24 h during CVVH. The plasma levels of TNF-α, IL-6, IL-10 and IL-18 were tested by ELISA. Results The survival time in control group was (15.4±5.2) h,CVVH group was (21.4±7.1) h,HVHF group was (22.4±6.7) h. The survival time in CVVH and HVHF group was significantly longer than that of control group (P< 0.05 ). Heart rate (HR), mean arterial blood pressure (MAP), central venous pressure (CVP) and cardiac output (CO) showed no significant differences among three groups. Plasma BUN and Ser increased gradually after the establishment of porcine endotoxemic shock model. BUN and Scr of CVVH and HVHF group were lower compared to control group (P<0.05), but there was no significant difference between CVVH and HVHF group (P>0.05). Plasma TNF-α and IL-6 peaked at T1, IL-10 peaked at TO, then they declined gradually. While IL-18 increased at TO and did not change after TO. A significant decrease of plasma IL-10 level was observed at T6, T12 and T24 in CVVH group compared with control group (P<0.05). HVHF group accomplished a greater decrease in plasma TNF-α (T6) and IL-10 (T6, T12, T24) levels compared with control group and CVVH group (P< 0.05). The levels of IL-6 and IL-18 showed no significant differences among three groups. There was a negative correlation between IL-6 and survival time (P<0.05). Conclusions HVHF and CVVH can prolong the survival time of porcine endotoxemic shock. IL-10 can be removed effectively with CVVH and HVHF. HVHF can also remove TNF-α effectively. CVVH and HVHF treatment can both remove BUN and Scr effectively. IL-6 is a powerful independent predictive factor for survival time of porcine endotoxemic shock.

Objective To determine the role of nuclear factor-?B(NF-?B) in ischemic acute renal failure (ARF) rats. Methods Gel mobility shift assay was used to detect the DNA binding activity of NF-KB in ischemic ARF rats and reverse transcription-polymerase chain reaction (RT-PCR) assay was used to study the expression of renal inducible nitric oxide synthase (iNOS) . The relationship between DNA binding activity of NF-?B and expression of iNOS was also analyzed. Results The DNA binding activity of NF-?B in renal cortex increased from 1.00 ?0.17 of controls to 3. 67 ? 1. 94 of 6 hours after ischemia-reperfusion ( P

Objective To assess the risk factors of intradialytic-hypotension (IDH) and the prognosis of IDH among maintenance hemodialysis (MHD) patients for the prevention and treatment of IDH.Methods 276 MHD patients were enrolled during Jan.2009 to Mar.2009.Intradialytic blood pressure was monitored during a 3-month period.IDH was defined as an event characterized by a sudden drop in systolic BP more than 20 mmHg or in mean artery pressure (MAP) more than 10 mmHgassociated with clinical events and need for interventions.Dialysis-related information was collected.Kaplan-Meier method,log-rank test,logistic regression and Cox regression analyses were performed to examine the association between IDH and survival,using a follow-up through 31 May 2014.Results A total of 276 patients were recruited.The incidence rate of IDH was 40.9％.163 patients with no-IDH (＜ 1/10 hypotensive events/3 months) served as controls.113 patients with IDH (≥ 1/10 hypotensive events/3 months) were identified among all 276 patients.Multivariate logistic regression analysis showed that age,ultrafiltration rate,gender,serum NT-proBNP,serum albumin and aortic rool inside dimension (AoRD) were associated with IDH among MHD patients.During the 5-year follow-up,74 patients died,with a mortality rate 5.2 per 100 person-year.Kaplan-Meier survival curve showed significant difference of overall and CV mortality rates between 2 groups.The multivariate Cox regression model indicated that IDH increased the risk of death (HR=1.572,95％CI 1.077-2.293,P=0.019).So did the rise of LVMI (HR=1.010,95％CI 1.009-1.085,P=0.020).Conclusion Elderly,female,high ultrafiltration rate,high level of serum NT-proBNP,hypoalbuminemia and shorter AoRD are independent risk factors for IDH among MHD patients.LVMI can predict the outcome of MHDpatients.Intradialytic hypotension is an independent risk factor for long-term mortality in MHD patients.

Objective To investigate the situation of prevalence,treatment and control of hypertension in patients with chronic kidney disease(CKD)by CROSS-sectional study. Methods Nine hundred out-patients with CKD in our department from November 2006 to March 2007 were enrolled in the study,including 480 male and 420 female.Among 900 CKD cases,354 patients underwent maintenance dialysis,including 228 on hemodialysis and 126 on peritoneal dialysis.Results The prevalence of hypertension in CKD patients was 80.2%(nude 83.5%vs female 76.4%,P<0.01).The prevalence of hypertension in patients on dialysis was significantly higher than that in non-dialysis patients(90.1%vs 73.8%,P<0.01),but there was no significant difference between hemodialysis and peritoneal dialysis cases.Antihypertensive treatment rate was 92.4%in CKD patients with hypertension.and was significantly higher in patients on dialysis than that in non-dialysis patients(95.6%vs 89.8%.P<0.01).The control rate according to current recommendations for CKD patients (BP<130/80 mm Hg) was very low. Control of both SBP and DBP was only achieved in 20.4% of non- dialysis patients. The control rate of hypertension (BP< 125/75 mm Hg) in patients with proteinuria >1 g/24 h was 8.4%. The proportion of dialysis patients with BP<140/90 mm Hg was significantly lower than that of non-dialysis patients (45.2% vs 55.5%, P<0.01). The percentage of hemodialysis patients with BP < 140/90 mm Hg was significantly higher than that of peritoneal dialysis patients (49.8% vs 36.5%, P<0.05). The prevalence of hypertension was associated with the decrease of renal function and the increase of age. The prevalence of hypertension in diabetic nephropathy was higher than that in primary glomerular diseases. Patients received 1, 2, 3 and 4 or more kinds of antihypertensive drugs accounted for 37.2%, 37.5%, 19.3% and 5.9% respectively. The combination of calcium channel blocker (CCB) and renin-angiotensin-aldosterone system (RAAS) inhibitors was more frequently used in CKD patients. The CCB was the most frequently prescribed drug (74.1% ), followed by angiotensin Ⅱ receptor blockers (ARB) (48.4%), angiotensin-converting enzyme inhibitors (ACEI) (25.6%) and alpha, beta-blockers (24.7%). Conclusions The prevalence of hypertension in CKD patients is quite high, which is associated with the progression of renal function, increase of age, the type of underlying kidney disease, obesity and diabetes mellitus. The control of hypertension is unsatisfied in CKD patients, especially in dialysis patients and those with overt proteinuria.

ObjectiveTo compare the efficacy and safety of intermittent patient-initiated single-dose antibiotic prophylaxis and continuous antibiotic prophylaxis for the prevention of recurrent urinary tract infection (UTI) in postmenopausal women. MethodsA randomized controlled clinical trial was conducted for the prevention of recurrent urinary tract infection. Single dose of antibiotic was given every night in continuous antibiotic prophylaxis group and every time after exposure to conditions predisposed to UTI in intermittent antibiotic prophylaxis group. The duration of prevention was 12 months in both groups. ResultsThe effective rates of intermittent antibiotic prophylaxis and continuous antibiotic prophylaxis were 71.0% and 81.8% respectively (P＞0.05). The incidence of gastrointestinal adverse reaction in intermittent antibiotic prophylaxis group was significantly lower than that in continuous antibiotic prophylaxis group (7.7% vs 28.6%,P＜0.05). ConclusionsCompared with continuous antibiotic prophylaxis, intermittent patient-initiated single-dose antibiotic prophylaxis is a better prophylaxis with less gastrointestinal adverse reactions for the prevention of recurrent urinary tract infection in postmenopausal women.

Objective To observe the efficacy of the treatment of mycophenolate mofetil (MMF) combined with prednisone on steroid-resistant idiopathic membranoproliferative glomerulonephrifis (IMPGN) patients with moderate to severe proteinufia. Methods Thirteen cases were diagnosed as IMPGN by renal biopsy after excluding secondary factors. Among 13 patients, 9 had severe proteinuria and another 4 had moderate proteinuria, 9 with hypertension and 11 with decreased renal function. Before MMF therapy, all of the cases were resistant to the treatment of glucocorticoid (prednisone 1 mg·kg-1·d-1) for 8 weeks or more. The dose of MMF was 1.5 g/d. Patients were followed up every month for blood pressure, urinary protein excretion, liver and kidney function, complete blood count, and adverse effects. Results At the initiation, the 24 h urinary protein excretion was (4.1±1.4) g, Scr (131.0±44.9) μmol/L, and estimated glomerular filtration rate (eGFR) (63.3±26.8) ml·min-1·(1.73 m2)-1. After prednisene therapy for at least 2 months, the 24 h urinary protein excretion (4.2±1.5) g, Ser (133.2±52.8)μmol/L and eGYR (63.3±27.1) ml·min-1·(1.73 m2)-1did not change significantly. After 3 months of the addition of MMF, 24 h urinary protein excretion declined slightly [(3.8±1.2) g, P>0.05]. After 6 months, 24 h urinary protein excretion declined significantly [(2.5±0.9) g, P<0.05], with decrease in Set and eGFR[(97.2±27.3) μmol/L and (81.3±24.2) ml·min-1·(1.73 m2)-1, P<0.05)]. At the end of 1 year, 24 h urinary protein excretion was only (1.5±0.6) g(P<0.01 ), Ser and eGFR were (95.9±22.5)μmol/L and (81.2±23.8) ml·min-1·(1.73 m2)-1(P<0.01). All the patients experienced a partial remission of proteinuria (urinary protein excretion decreased by 50% or more). Adverse event including stomach upset was found in 1 patient. Conclusion MMF combined with glucosteroids can effectively decrease proteinuria and improve renal function without obvious side effect in steroid-resistant IMPGN.

Objective To investigate the effects of repeated low dose intravenous infusion of low molecular weight iron dextran and iron sucrose on oxidative stress in chronic renal failure (CRF) rats. Methods CRF model was established by 5/6 subtotal nephrectomy (5/6 Nx). Four weeks after removing the right kidney, successful rats were randomly divided into low molecular weight iron dextran group, sucrose iron group and CRF control group. The sham group was established simultaneously. The dose of iron administrated in each rat was similar in iron dextran group and sucrose iron group. There were 6 rats in each group. Animals were observed for 6weeks, then the blood, urine and renal tissue samples were collected, and indexes of renal function,anemia, iron status and oxidative stress were investigated. Results The hemoglobulin (Hb) level in iron groups was significantly higher as compared to control group (P＜0.05) but was not significantly different between two iron groups. The levels of serum iron, ferritin and saturation rate of transferring (TS) were obviously lower in control group as compared to sham group (P＜0.05).Levels of above 3 indexes were significantly higher in two iron groups as compared to control group (P＜0.05), but were not significantly different between two iron groups. Concentration of plasma advanced oxidation protein products (AOPP) was obviously higher in two iron groups than that in control group [(127.84±21.19) μmol/L, (134.21±29.38) μmol/L vs (81.83±19.93) μmol/L, P＜0.05]. Plasma malonaldehyde (MDA) was significantly higher in iron sucrose group than that in iron dextran group [(6.06±0.73) nmol/L vs (4.99i0.80) nmol/L, P＜0.05]. Serum levels of superoxide dismutase (SOD) and total anti-oxidant capacity (TAOC) had no significant differences among three CRF groups. Concentration of plasma glutathione peroxidase (GSH-Px) was significantly decreased in three CRF groups as compared to sham group (P＜0.05), while plasma GSH-Px was significantly lower in sucrose iron group than that in iron dextran group and control group [(2123.11±74.78)nmol ·ml-1 ·min-1 vs (2352.84±163.90) nmol· ml-1 ·min-1, (2310.23±125.99) nmol ·ml-1 ·min-1, P＜0.05]. Conclusions Injection of intravenous iron can partially improve the anemia and the iron status indexes in 5/6 Nx CRF rats. Repeated low dose intravenous infusion of iron dextran and iron sucrose can aggravate the oxidative stress state in CRF rats, and the iron sucrose is worst.

Objective To investigate the location and expression of hypoxia inducible factor (HIF) subunits in the remnant kidney of 5/6 nephrectomy rats. Methods Remnant kidneys were produced in adult male SD rats by 5/6 nephrectomy. The renal function and histopathological changes were evaluated at week 1, 2, 4, 6, 8 and 12 after operation. Tissues of remnant kidneys were collected to detect the location and expression of HIF-1α and HIF-2α by immunohistochemistry staining and Western blotting. The mRNA levels of HIF targeted genes vascular endothelial growth factor (VEGF) and heme oxygenase-1 (HO-1) were determined by RTPCR. Results (1) 5/6 nephrectomy rats underwent one week of acute renal failure at first[Scr (122.8±22.1) μmol/L] and then developed compensative chronic renal failure [(66.0±3.7)-(66.4±8.4) μmol/L], but the level of Scr increased quickly after week 6 [(66.4±8.4)-(127.8±22.7) μmol/L],concomitantly with progressive tubulointerstitial fibrosis in remnant kidney cortex. (2) In cortex, HIF-1α was expressed only in the atrophic and dilated tubular cells while HIF-2α was located in endothelial, interstitial fibroblasts, and vascular smooth muscle cells. The semiquantitative results of imunohistochemistry and Western blotting revealed that HIF-1α and HIF-2α were both gradually up-regulated during the early stage of remnant kidney, peaked at week 4 and 6, and then gradually down-regulated. (3) The mRNA levels of HIF targeted genes VEGF and HO-1 transiently peeked at week 4 and 6, and then decreased gradually. Conclusions The increased stabilization of HIF-αprotein and transcription of HIF targeted genes at the early stage of this model is a compensation reaction towards hypoxia. The mechanism of decreased expression of HIF-α at the end stage of chronic kidney disease deserves further investigation.

Objective To explore the effects of Dimethyloxalyl Glycine(DMOG)on isehemic acute renal failure(iARF)in mice and its relationship with activation of hypoxia inducible factor 1α(HIF-1α).Method Twenty five C57/BL male mice were divided into 5 groups randomly:control group,DMOG group,sham operation group,ischemia/reperfusion(I/R)group and DMOG pretreated group(DMOG+I/R).Ischemia/reperfusion injury was induced in mice by clamping both renal pedicles for 30 minutes.The expression of HIF-1α was determined by Western blot.Renal function was reflected by blood urea nitrogen(BUN)and serum creatinine(Scr).Morphologic changes were evaluated under light microscopy.Apoptosis in the kidney was detected by TUNEL staining.Expression of Vimentin,a marker of tubulointerstitial damage was detected by immunohistochemistry.Results The elvated levels of of BUN((65.8±2.6) vs (13.6±0.7),P＜0.01],and Scr[(229.5±11.2) vs (6.5±0.8),P＜0.01]andwere found morphological injury were induced by the ischemic insult in I/R group.Administration of DMOG dramatically improved renal function[BUN,(26.3±6.5)vs(65.8±2.6);Scr,(27.0±14.1)vs(229.5±11.2),P＜0.01]associated with amelioration of tubulointerstital damage.In the DMOG treated group,the protein level of HIF-1α in the kidney of mile was also up-regulated significantly.Conclusions The protection against iARF in mice by DMOG administration is mediated by activation of HIF-1α.

Objective To investigate the association between peripheral white blood cell count including its subtypes and cardiovascular disease (CVD) incidence and one-year all-cause mortality in maintenance hemodialysis (MHD) patients.Methods A total of 371 MHD patients at Zhongshan Hospital,Fudan University between March 2009 and February,2011 were enrolled.Demographic,hematological,nutritional and inflammatory markers were obtained.All patients were followed for one year to investigate the risks for CVD event and mortality.Spearman correlation and linear regression were used to assess the relationship between white blood cell count and other laboratory parameters.Difference in categorical factors between two groups were determined with Chi-square test,Difference in continuous values between two groups were assessed with t test.Kaplan-Meier analysis and Cox proportional hazards model were applied to assess one-year mortality predictors.Results Patients with CVD event had lower lymphocyte count level (1.17±0.38 vs 1.34±0.51,P＜ 0.05) and higher monocyte count level (0.44 ± 0.15 vs 0.37 ± 0.15,P＜0.01) than those without CVD event.Cox proportional hazard regression showed that an increased lymphocyte count was associated with reduced mortality risk,95％CI:0.136-0.719,P ＜ 0.01) and that an increased monocyte count was associated with increased mortality risk,95％ CI:2.657-74.396,P＜0.01) after adjustment for hsCRP.Conclusion Decreased lymphocyte level and increased monocyte level are significantly related to CVD event and are independent predictors of increased one-year all-cause mortality risk in MHD patients.