Objective To evaluate the efficacy and safety of midodrine hydrochloride in the treatment of intradialysis hypotension (IDH) in maintenance hemodialysis (MHD) patients. Methods One hundred and fourteen MHD patients from 8 dialysis centers with IDH were enrolled in the study. These patients took orally midodrine for 4~6 weeks. Midodrine (2.5~10 mg) was given 15~30 minutes after the beginning of hemodialysis, and another 2.5~10 mg was used during hemodialysis if systolic blood pressure(SBP) increased less than 20 mm Hg. The total usage of each dialysis session was not more than 20 mg. The pre-, intra-, post-hemodialysis blood pressure and heart rate, the pre- and post-hemodialysis body weight, the ultrafiitrated volume of each dialysis, the pre- and post-treatment liver and renal function and electrocardiogram were measured and recorded. The symptoms of IDH were observed. Results Compared to those before treatment with midodrine hydrochloride, the minimum intradialysis SBP and heart rate at that time, the post-dialysis SBP and heart rate, and total ultrafiitrated volume changed significantly (P<0.01). The total effective rate was 84.2%. And the symptoms of IDH were improved significantly (P<0.01). The side effects were observed in only 2 patients. Conclusion Midodrine is safe and effective for the treatment of IDH.

Objective To describe the circadian profiles of interdialytic blood pressure in maintenance hemodialysis patients and to investigate its related factors. Methods Ambulatory blood pressure monitoring (ABPM) was conducted in forty-four patients on regular hemodialysis during interdialytic days. Three groups were identified with their ambulatory blood pressure: non-hypertension group, controlled hypertension group and uncontrolled hypertension group. Hemoglobin, creatinine, Kt/V, serum total calcium, serum phosphate, immunoreactive parathyroid hormone(iPTH), interdialytic weight gain and Morisky self-report scale etc. were assessed. Results (1) No significant difference was found in ABPM index ranged from decline in nocturnal systolic and diastolic blood pressure, AASI to dipper percentage in three groups. Nevertheless, 24-h average pulse pressure in uncontrolled hypertension group was higher than the other groups [（80.06±13.41） vs （53.00±7.73）, （57.85±21.97） mm Hg, all P<0.01]. (2) All the three groups showed the blood pressure profile of double-peak and trough. In the uncontrolled hypertension group, however, the nocturnal blood pressure decrease was not notable. (3) Nocturnal systolic blood pressure decline was negatively correlated to iPTH (r=－0.039, P<0.05). (4) In ten dippers out of all 44 patients, AASI was negatively correlated with nocturnal diastolic blood pressure decline (r=－0.748, P<0.05). Conclusion Nocturnal blood pressure decline is correlated to iPTH and arterial sclerosis.

Objective To explore the effects of intra-jugular vein dual lumen catheter lock heparin in different concentrations on the coagulation function, hemorrhagic tendency and catheter thrombosis risk in hemodialysis patients, and to investigate the reasonable lock heparin concentration. Method Ninety end stage renal disease (ESRD) patients receiving regular hemodialysis were enrolled and randomly assigned into 3 groups(n=30): Group A (pure heparin lock solution, 6250 U/ml), Group B (medium heparin lock solution, 1040 U/ml) and Group C (low heparin lock solution, 625 U/ml). The coagulation indexes were determined in short term. Complications such as bleeding, thrombosis, infection and thrombocytopenia were monitored. Results Prothrombin time(PT), activated partial thromboplastin time (APTT) and thrombin time(TT) were significantly prolonged in Group A（P<0.01）; only APTT was significantly prolonged in Group B; however, no significant changes were observed in Group C. Hemorrhage risk was much higher in Group A than that in Group B and C (26.7% vs 10% and 0， P<0.05). Catheter thrombosis incidence was significantly higher in Group C than that in Group A and B (23.3% vs 0 and 10%， P<0.05). Only 1 suspected catheter related infection was found in Group C, and 2 cases of moderated thrombocytopenia in Group A. Conclusion Moderate concentration of lock heparin solution has the best balance of hemorrhagic and thrombotic risk, and should be recommended to most of regular hemodialysis patients.

Objective To study the arterial stiffness in maintenance hemodialysis (MHD) patients and to explore the associated factors. Methods Ninety MHD patients and 36 healthy controls were enrolled in the study. Automatic pulse wave velocity (PWV) measuring system was applied to examine carotid-femoral pulse wave velocity (CFPWV) and carotid-radial PWV (CRPWV) as the parameters reflecting central elastic large arterial and peripheral muscular medium-sized arterial elasticity respectively. Blood pressure and biochemical parameters were detected. Backward multiple linear regression analysis was used to assess the influencing factors of arterial stiffness. Results CFPWV and CRPWV in MHD patients were greater than those of healthy controls[(13.22±3.23) m/s vs (10. 67±2.11) m/s and (9.58±1.87) m/s vs (8.81±1.09) m/s, all P<0.05]. Backward multiple regression analysis demonstrated that age and pulse pressure were positively correlated with CFPWV , while dialysis duration, calcium phosphorus product, parathyroid hormone, low density lipoprotein and mean arterial blood pressure were significantly correlated with CRPWV. Volume reduction after single dialysis session could not improve arterial stiffness of MHD patients. Conclusions Arterial stiffness of large artery and peripheral muscular medium-sized artery increases in MHD patients. Age and pulse pressure are major determinants of large artery stiffness. Peripheral muscular medium-sized arterial stiffness is more easily influenced by dialysis-associated factors.

Objective To investigate the association between arterial stiffness of the common carotid artery(CCA) and insulin resistance in hemodialysis patients. Methods Arterial stiffness index β of CCA was evaluated by an ultrasonic phase-lock Echo-tracking system in 80 stable non-diabetic hemodialysis patients. Insulin resistance was detected by the homeostasis model assessment method (HOMA-IR). Plasma hemoglobin, serum albumin, total cholesterol, high density lipoprotein, low density lipoprotein, triglyceride, lipoprotein (a), ApoA1, ApoB, CRP, calcium, phosphorus and creatinine were determined by standard methods. Results The stiffness index β was 11.41±4.13 in patients with previous cardiovascular disease(CVD) and 9.75±3.63 in those without CVD(P<0.05). The stiffness index β was positively correlated with HOMA-IR（r=0.321，P<0.01）, as well as with age（r=0.376，P<0.01）, pulse pressure（r=0.267，P<0.05）, and duration of hemodialysis（r=0.219，P<0.05）. In stepwise multiple regression analysis, HOMA-IR（β=0.228，P<0.05）and age （β=0.308，P<0.01） were identified as significant independent variables for stiffness index β of CCA. Conclusions Insulin resistance is associated with arterial stiffness in non-diabetic hemodialysis patients. The increased arterial stiffness may be the link between insulin resistance and cardiovascular morbidity as well as mortality in hemodialysis patients.

Objective To investigate the effects of continuous venovenous haemodiafiltration（CVVHDF） on major organ function and plasma cytokine levels in MODS dogs. Methods Fifteen Beagle dogs were subjected to hemorrhagic shock plus resuscitation and endotoxemia to establish MODS model, then dogs were randomly divided into 2 groups: CVVHDF group (n=8) and MODS group without CVVHDF (n=7). CVVHDF was performed for 12 hours after endotoxin injection in CVVHDF group dogs. Serum ALT, AST, Scr, BUN and blood gas were routinely measured, and plasma TNF-α, IL-6 and IL-10 concentrations were measured by ELISA at different time points. Results Plasma levels of IL-6 and IL-10 were significantly decreased in the CVVHDF group at 3 h, 6 h, 9 h and 12 h after endotoxin injection as compared with MODS group (P<0.01). TNF-α levels were similar in both groups(P＞0.05). IL-6 and TNF-α were detected in the ultrafiltrate. The sieving coefficients (SC) for IL-6 and TNF-α were 0.27±0.13 and 0.1±0.1 respectively. IL-10 could not be detected in the ultrafiltrate. In CVVHDF group, function of major organs was improved. The beneficial effect of CVVHDF on the hypotension of MODS dogs was particularly striking at 6 h, 9 h, and 12 h after endotoxin injection（P<0.01）. Mean PaO2 in CVVHDF groups at 3 h, 6 h, 9 h, and 12 h after endotoxin injection was significantly higher than that in MODS group（P<0.01）. Conclusion CVVHDF effectively removes IL-6 and IL-10 from the circulation, attenuates endotoxin-induced hypotension and improves arterial oxygenation in MODS dogs.

Objective To investigate the microinflammatory state and its relationship with atherosclerosis and cardiac function in patients on continuous ambulatory peritoneal dialysis（CAPD）. Methods Sixty-seven CAPD patients, 27 non-dialytic stage 5 chronic kidney disease（CKD 5）patients and 27 gender and age matched healthy controls were enrolled in this cross-sectional study. Clinical data and biochemical parameters were collected. Serum interleukin-6（IL-6）and IL-10 levels were measured by enzyme-linked immunosorbent assay（ELISA）. High-sensitivity C-reactive protein（hs-CRP） was measured by immunoturbidimetry. Prevalence of atherosclerosis was detected by carotid ultrasonography while cardiac function was detected by echocardiography. Results Serum levels of inflammatory biomarkers were elevated significantly in CAPD and CKD 5 patients as compared with healthy controls [ IL-6(ng/L): 2.400, 1.515 vs 0.698; IL-10(ng/L): 1.988, 1.958 vs 0.277; hs-CRP(mg/L): 1.090, 1.345 vs 0 ]. Left ventricular mass index（LVMI）, myocardial performance index（Tei index 0.75±0.31, 0.66±0.27 vs 0.52±0.23）in CAPD and CKD 5 patients increased significantly. The prevalence of carotid artery atherosclerosis and left ventricular hypertrophy（LVH）in CAPD and CKD 5 patients was significantly higher than that in healthy controls. No significant difference of the ultrasonic parameters was found between CAPD and CKD 5 patients. In CAPD patients, IL-6 was positively correlated with Tei index, whereas IL-10 was negatively correlated with LVMI and was positively correlated with ejection fraction（EF）. In a multiple regression model, IL-6, self-rating depressive scale（SDS）score and pulse pressure were independent predictors of carotid artery atherosclerosis. Similarly, IL-6 and primary hypertension were independent correlates of Tei index in CAPD patients. Conclusions Microinflammatory state exists in either non-dialytic CKD 5 patients or CAPD patients and it is associated with atherosclerosis and cardiac disfunction. IL-6 is an independent risk factor of atherosclerosis and increased Tei index in CAPD patients.

Objective To study the effect of uremic serum on the calcification and osteogenic transition of cultured human umbilical artery smooth muscle cells (HUASMC). Methods Sera from 40 healthy controls (control group), 40 nondialysis uremic patients (nondialysis group) and 45 uremic patients on dialysis (dialysis group) were detected for biochemical indexes concerned and used to treat the cultured HUASMC. Alizarin red S stain was applied to examined calcium deposition in the cell layer. Calcium concentration was determined calorimetrically by the O-cresolphthalein complexone method, and corrected by total cell proteins. The mRNA expression of bone specific alkaline phosphatase (BAP), osteopontin (OPN) and bone morphogenetic protein 2 (BMP2) was estimated by realtime PCR. OPN and BMP2 protein expression was assessed by Western blotting and fluorometry method was used to check the BAP concentration. Results Serum biochemical detection revealed that both uremic groups had higher levels of phosphate, triglyseride, iPTH, C-reactive protein(CRP) and IL-6, and lower level of fetuin-A than healthy control（P<0.05）. Furthermore, dialysis serum had higher levels of triglyseride, CRP and IL-6 than nondialysis serum（P<0.05）. Compared with control group, both uremic sera induced more cell layer calcium deposition and higher mRNA and protein expression levels of BMP2, BAP and OPN（P<0.05）. Higher mRNA and protein expression levels of above factors were found in dialysis group as compared to nondialysis group（P<0.05）. Conclusions Uremic serum can induce HUASMC calcification and osteogenic transition in vitro, which may be one of the mechanisms involved in vascular calcification of ESRD patients. Microinflammatory state may promote the osteogenic transition and vascular calcification in dialysis patients.

Objective To observe the effects of calcitriol on cellular proliferation and apoptosis, and on the expression of transforming growth factor-β1 (TGF-β1)-induced α-SMA and extracellular matrix（ECM） synthesis in renal interstitial fibroblasts, so as to illustrate its potential roles and underlying mechanisms in preventing renal interstitial fibrosis. Methods In NRK-49F of cultured rats in vitro, cellular proliferation was detected by MTT. The cellular cycle and apoptosis were assessed by flow cytometry using annexin-V FITC/propidium iodide(PI). Real-time PCR was performed to detect the mRNA expression of α-SMA, CTGF and FN, and Western blot was performed to detect the protein expression of α-SMA and FN. Results Cellular proliferation was inhibited by calcitriol through G1-arrest (P<0.05). But calcitriol had no effect on cell apoptosis (P>0.05). Increased expression of α-SMA, CTGF and FN mRNA induced by TGF-β1 were significantly suppressed by calcitriol as compared with TGF-β1 treated group (P<0.05). However, there was no significant difference among the groups with various concentration of calcitrol (P>0.05). The similar phenomenon of the level of α-SMA and FN protein expression was observed in all groups by Western blot. Conclusion Calcitriol inhibits cellular proliferation of renal interstitial fibroblast by G1-arrest, but has no effect on cell apoptosis, and can prevent renal interstitial fibrosis caused by TGF-β1.

Objective To observe the expression of heparanase (HPA) in kidney of diabetic nephropathy (DN) rats and to investigate the role of HPA in the pathogenesis of proteinuria in DN rats. Methods DM rat models induced by intraperitoneal injection with streptozotocin were constructed. Twenty-six rats were randomly divided into healthy control group (n=6), DM 6-week group(n=10) and DM 12-week group(n=10). Relative kidney weight（RKW）, blood glucose, BUN, Scr, 24-hour urine volume and 24-hour proteinuria quantitation were measured, and renal morphology was observed after 6 and 12 weeks. The expression of HPA was examined by immunohistochemistry and reverse transcription PCR. Results (1) Compared with the control group, RKW, blood glucose, BUN, 24-hour urine volume and 24-hour proteinuria quantitation of DM groups increased markedly(P< 0.05 or P<0.01).(2) Compared to the control group, the expression of HPA mRNA and protein in DM groups increased significantly (P<0.01). (3) HPA protein and mRNA were positively correlated with the quantification of urinary protein (r=0.783, P<0.01; r=0.793, P<0.01). Conclusion The increased expression of HPA maybe participate in the pathogenesis of proteinuria in DN.

Objective To evaluate the improvement of diagnostic accuracy with background region of interest(ROI) rectification for 99mTc-DTPA renography in patients with GFR≤30 ml·min-1·（1.73 m2)-1, and to compare with plasma clearance of 99mTc-DTPA (GFRp, dual plasma sampling method). Methods Thirty-three patients(age>20 years, male/female =13/20) with severe chronic kidney disease[GFR≤30 ml·min-1·（1.73 m2)-1] were enrolled in this study. A dose of 111 MBq/0.5 ml of 99mTc-DTPA was injected into an antecubital vein. The background ROI was selected below the kidney(Gates method, method a)or around the kidney(method b), then these two different GFR (GFRa, GFRb)were automatically estimated by computer. Meanwhile, 3 ml blood samples were collected 2 h and 4 h after injection respectively, and radioactivity of 1 ml plasma was measured. GFR was calculated by dual plasma sampling method (GFRp) and the results were all standardized with the body surface area. The accuracies and correlations of GFRa and GFRb were compared to GFRp respectively. Results The correlation coefficients were ra=0.602 and rb=0.834. The median of difference of GFRa and GFRb was 8.33, -4.41. The median of absolute difference of GFRa and GFRb was 8.33, 4.49. The accuracies within ±15%, ±30% and ±50% of GFRa were 24.2%, 30.3% and 48.5%, and those of GFRb were 33.3%, 51.5% and 81.8%. Conclusion The background ROI around kidney can obviously improve the diagnostic accuracy of 99mTc-DTPA renography in patients with severe renal insufficiency.