Chinese Journal of Nephrology

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Analysis of clinicopathology and plasmapheresis efficacy in patients with anti-glomerular basement membrane disease

MOU Li-jun;CHEN Li-meng; ZUO Lai-meng;WEN Yu-bing;LI Hang;QIN Yan;LI Ming-xi;TAO Jian-ling;YE Wen-ling;XU Hong;YE Wei;SUN Yang;LI Xue-mei;LI Xue-wang

2011, 27(4): 230-235.

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Objective To analyze the clinicopathological features and prognosis of anti-glomerular basement membrane (GBM) disease, and evaluate the efficacy and safety of double filtration plasmapheresis (DFPP). Methods A total of 35 hospitalized patients diagnosed as anti-GBM disease in our department were enrolled in the study. All the patients were divided into 3 groups according to the manifestations at admission. Group Ⅰ: 24 patients with severe pulmonary hemorrhage or rapidly progressive glomerulonephritis (RPGN) received pulse methylprednisolone with or without DFPP, and then followed by prednisone and CTX. Group Ⅱ: 5 patients without severe pulmonary hemorrhage and RPGN received prednisone and CTX. Group Ⅲ: 5 ESRD patients and 1 normal renal function patient did not receive immunosuppression therapy. Anti-GBM antibody titer of pre- and post-DFPP in 4 patients was measured consecutively, and removal rate was calculated. Results The mean age of all the patients was (41.1±16.6) years. Sixteen patients (45.7%) presented Goodpasture's syndrome. Eighteen patients (51.4%) had anti-GBM glomerulonephritis alone, whereas one suffered solely from pulmonary hemorrhage. 20% patients had positive P-ANCA serology. 54.2% crescentic glomerulonephritis and 7 with other glomerulonephritis were revealed by kidney biopsy in 24 patients. Patients in Group Ⅰshowed more severe manifestation at admission: higher Scr level, higher titer of anit-GBM antibody, greater percentage of crescents. Within the follow-up period, 7 patients died and kidneys of 50% patients survived. No patient died in Group Ⅱand Ⅲ. The elder age, anemia, higher Scr (>300 μmol/L), oliguria or anuria, emergency hemodialysis at admission, and more glomerular sclerosis were predictors of poor prognosis. The anti-GBM antibody was negative after 4 to 6 sessions of DFPP, and the mean removal rate was 55%. During total 94 DFPP sessions, there was no unacceptable morbidity. Conclusions Different therapy strategy is necessary for anti-GBM disease with different clinical manifestations. DFPP is an effective and safe clearance way of anti-GBM antibody.

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Efficacy analysis of high-flux hemofiltration in the treatment of sepsis

LV Hong-yun;ZHANG Ping;CHEN Jiang-hua

2011, 27(4): 236-242.

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Objective To analyze the risk factors of sepsis, and to elucidate the efficacy of high-flux hemofiltration (HVHF) in the treatment of sepsis and the initiate opportunity of HVHF treatment on sepsis complicated with acute kidney injury (AKI). Methods Clinical data of 152 patients with sepsis undergoing HVHF treatment were retrospectively analyzed. APACHEⅡ,APACHEⅢ and SAPSⅡ score evaluation before treatment and 24 h, 48 h, 72 h after treatment were performed. According to 28-day survival, patients were divided into survival group and death group. Clinical indicators before and 24 h, 48 h, 72 h after treatment were compared between groups. Risk factors influencing prognosis of patients were examined by multivariate regression analysis. Influence of AKI stages on prognosis of patients was studied. Results Lung and alimentary tract were the most frequent infection sites of sepsis. Twenty-eight days after HVHF treatment, 74 patients (48.68%) survived, seventy-eight patients (51.32%) died among 152 patients, and 4 patients(2.63%) needed sequent renal replacement therapy. Twenty-eight-day mortality was significantly lower than the mortality 88.78%±17.72% predicted by APACHE Ⅲ. APACHEⅡ, APACHE Ⅲ and SAPSⅡ scores decreased remarkably (P<0.01) 24 hours after treatment. Age, number of dysfunctional organ, APACHEⅡ, APACHEⅢ, SAPSⅡ scores, underlying diseases, shock, AKI, severe acute pancreatitis, alimentary tract hemorrhage, cataphora and pressor agent were correlated with 28-d survival rate. Underlying diseases and APACHE Ⅲ were independent risk factors. Renal function recovery rate in AKI stage 1 was higher than that in AKI stage 2, 3 (P<0.05). Twenty-eight-day mortality of patients without AKI was lower compared to AKI stage 1, 2, 3 (P<0.05), but 28-day mortality was not significantly different among AKI stage 1, 2, 3. Conclusions Prognosis of patients with sepsis is poor. HVHF can improve biochemical indicators and prognosis of patients effectively, and increase survival rate. Underlying diseases and APACHE Ⅲ are independent risk factors of 28-day mortality of sepsis patients. Twenty-eight-day mortality of non-AKI patients is obviously lower compared to AKI stage 1, 2, 3 patients. AKI stage is correlated with 28-day renal function recovery rate, but not obviously correlated with 28-day mortality.

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A randomized controlled trial of efficacy and safety of PES14LF polyethersulfone dialyzer on hemodialysis patients

ZHANG Wei-ming;JIANG Geng-ru;QIAN Jia-qi;WANG Bing-shun;ZHU Chun;WANG Yong-mei;HUANG Hai-dong;YAN Yu-cheng;NI Zhao-hui

2011, 27(4): 243-246.

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Objective To evaluate the efficacy and safety of PES14LF polyethersulfone highflux dialyzer on maintenance hemodialysis (MHD) patients. Methods A total of 72 MHD patients from two hospitals in Shanghai were enrolled in a randomized parallel controlled study. Conventional hemodialysis was performed for 4 h with PES14LF dialyzer in trial group and with German F6 dialyzer in control group. For each patient the study lasted one week. The clearances of urea, creatinine and phosphate were calculated. Adverse event and adverse reaction were recorded. Results There were no significant differences of urea and creatinine clearance and reduction ratio between trial and control group. The phosphate clearance in trial group was significantly higher than that in control group [(144.57±27.83) ml/min vs (117.15±22.77) ml/min, P<0.05]. There was no significant difference of phosphate reduction ratio between trial and control group. The efficiency of urea clearance and urea reduction ratio achieved clinic effective target in two groups and no significant differences in above indexes between two groups were found. Conclusion PES14LF dialyzer is effective and safe for clinical application.

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Interdialytic body weight gain and associated factors in maintenance hemodialysis patients

CHEN Yue-mei;DING Xiao-qiang;TENG Jie;ZOU Jian-zhou;LIU Zhong-hua;WANG Yi-mei;SHEN Bo;CAO Xue-sen

2011, 27(4): 247-252.

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Objective To study interdialytic body weight gain (IBWG) in maintenance hemodialysis (MHD) patients, and to analyze the associated factors. Methods A total of 269 patients undergoing maintenance hemodialysis were enrolled in this cross-sectional study. The patients were divided into two groups according to the percentage of IBWG (PIBWG: interdialytic body weight gain/dry weight×100%): PIBWG>3.50% (190 cases) and PIBWG≤3.50% (79 cases). Associated factors of IBWG were analyzed. Results The average IBWG of 269 MHD patients was (2.42±1.01) kg (0-6.33 kg), and PIBWG was (4.25±1.79)%. In male patients, IBWG was (2.45±1.09) kg, and PIBWG was (3.99±1.79)%. In female patients, IBWG was (2.39±0.85) kg, and PIBWG was (4.64±1.74)% which was significantly higher compared to males (P<0.01). Patients with PIBWG＜3.00% accounted for 20%, with PIBWG≥3.00% to ＜5.00% accounted for 50%, with PIBWG≥5.00% accounted for 30%. Compared to patients with PIBWG>3.50%, those with PIBWG≤ 3.50% were characterized by elder age (year) (60.50±14.49 vs 54.07±13.78), more males ( 70.88% vs 54.74%), shorter dialysis duration (month) (41.03±41.92 vs 58.83±43.57), larger BMI (kg/m2) (22.67±3.36 vs 20.91±3.25) and less dry weight (kg) (56.69±10.94 vs 62.82±10.97), more residual urine (ml, In) (6.19±0.94 vs 5.48±0.8), lower predialysis serum β2-MG (mmol/L) (31.61±9.82 vs 38.54±10.38) and phosphorus(mmol/L) (1.92±0.66 vs 2.15±0.58). Correlation analysis revealed that PIBWG was positively correlated with dialysis duration, Scr, BUN, β2-MG, phosphorus, decrease and decrease percentage of BP during hemodialysis, and negatively correlated with age, dry weight, BMI, residual urine, and pre-dialysis SBP, MAP. Conclusions PIBWG of about 70% of our patients was below 5%. Young, female, low BMI and dry body weight, long dialysis duration, low residual urine, chronic glomerulonephritis and diabetic nephropathy are associated with more IBWG, which may lead to greater intradialytic BP fluctuation.

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Clinical study on biocompatibility of four dialyzers with different membranes

LIU Jing;FENG Ling;ZHANG Dong-liang;CUI Wen-ying;JI Dan-ying;ZHANG Yue;LIU Wen-hu

2011, 27(4): 253-258.

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Objective To elucidate the biocompatibility differences of 4 dialyzers with different membranes in maintenance hemodialysis (MHD) patients. Methods A total of 60 MHD patients were enrolled in the prospective, randomized, control, cohort study. In baseline, synthetic polysulfone (PS) membrane dialyzer was used in all the patients for at least 3 months. Then the patients were randomly divided into three groups: ployethersulfone (PES) membrane group, cellulose triacetate (CTA) membrane group, and synthetic polymethylmethacrylate (PMMA) membrane group. Study duration was 6 months. No dialyzer was reused. The biocompatibility markers were detected repeatedly at different time points and compared with each other in different dialyzer groups. Results The blood levels of high sensitive C reactive protein, interleukin-1β and interleukin-13 were not significantly different among different groups on every time point. However, the blood complements levels and WBC count were significantly different among four kinds of dialyzer. When the dialyzers changed from PS to PMMA membrane, C3a levels and WBC count changed significantly (P<0.05). Moreover, the change of C5a level was significantly different between PES group and PMMA group on month 3 (P<0.05). Conclusion There are some differences of biocompatibiliy among different dialyzer membranes.

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Risk factors for aortic and mitral valve calcification in maintenance hemodialysis patients

CAO Xue-sen;ZOU Jian-zhou;TENG Jie;ZHONG Yi-hong;JI Jun;LIU Zhong-hua;SHEN Bo;DING Xiao-qiang

2011, 27(4): 259-265.

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Objective To explore the potential risk factors for aortic and mitral valve calcification in maintenance hemodialysis (MHD) patients. Methods Patients on MHD for at least 6 months, aged≥18 years without history of surgery or catheter for heart valve disease were enrolled in the study. Echocardiographic examination was performed to detect the calcification. The risk factors for aortic and mitral valve calcification were analyzed by Logistic regression. Results One hundred and eighty-one MHD patients (98 men and 83 women) were enrolled in the study. Of all the patients, aortic or mitral valve calcification was found in 94 patients (51.9%), aortic valve calcification in 90 patients (49.7%), mitral valve calcification in 30 patients (16.6%), aortic and valve calcification in 26 patients (14.4%). Multivariate Logistic regression showed that age (β=5.52, P=0.007), dialysis duration (β=6.99, P=0.039) and pre-albumin (β=-12.616, P=0.004) were independently correlated with aortic valve calcification. Mitral valve calcification was independently correlated with dialysis duration (β=6.057, P=0.002), history of primary hypertension (β=3.054, P=0.008), hemoglobin (β=-0.061, P=0.035) and β2 microglobulin (β=7.63, P=0.01). While the correlation between mitral valve calcification and age was borderline significant (β=0.085, P=0.05). Conclusions Valve calcification is prevalent in MHD patients, and aortic valve calcification is more common than mitral valve calcification. Age, dialysis duration and low serum pre-albumin are independent risk factors for aortic valve calcification. The risk factors for mitral valve calcification include age, dialysis duration, history of primary hypertension, anemia and high serum β2 microglobulin.

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Effect of parathyroid hormone on renal anemia in patients with chronic kidney disease

MU Lin;FU Shu-xia

2011, 27(4): 266-270.

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Objective To observe the mechanism of elevated parathyroid hormone（PTH）leading to erythrocytes life span shortened in the patients with chronic kidney disease(CKD). Methods Serum samples of 30 healthy people and 75 CKD patients were collected. Patients were divided into three groups according to their renal function. Intact parathyroid hormone (iPTH) was detected by immunochemiluminometry. The erythrocytes phosphatidylserine (PS) exposure and intracellular calcium concentration ([Ca2+]i) were measured by flow cytometry. Results (1)Levels of serum iPTH, [Ca2+]i and erythrocytes PS exposure increased gradually with the decline of renel function in stages 3 to 5 of CKD, the differences were significant with CKD 1 to 2 stages and healthy control group (all P<0.05). (2)Pearson correlation analysis revealed, during CKD 3 to 5 stages, Hb was negatively correlated with iPTH and erythrocyte PS exposure respectively (r=-0.830 and -0.791, all P<0.01); iPTH was positively correlated with [Ca2+]i and erythrocyte PS exposure (r=0.882 and 0.924, all P<0.01), whereas negatively correlated with serum Ca respectively (r=-0.544, P<0.01); erythrocyte PS exposure was positively correlated with [Ca2+]i (r=0.923, P<0.01) and not correlated with serum Ca (r=-0.138, P=0.365). (3)The linear regression equation of[Ca2+]i (Y) for iPTH (X) was Y=3.327+0.213X(F=21.529, P<0.05). The multiple linear regression equation of erythrocytes PS exposure (Y) for PTH (X1) and [Ca2+]i (X2) was Y=-0.303+0.283X2+0.139X1 (F=6.59, P<0.01). Conclusions By increasing intracellular calcium, iPTH can lead to an increase of the erythrocyte PS exposure, which will cause the occurrence of erythrocytes life span being shortened. As a result, the renal anemia will become more severe.

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Aspirin can reduce serum C reactive protein level in maintenance hemodialysis patients

HUANG Yan-ling;ZHONG Yi-hong;DING Xiao-qiang;ZHOU Jian-zhou;TENG Jie;LIU Zhong-hua;WANG Yi-mei;SHEN Bo

2011, 27(4): 271-275.

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Objective To identify the efficacy and safety of aspirin in reducing the serum high sensitivity C reactive protein (hsCRP) level and preventing the internal arteriovenous fistulas(AVF) embolism in maintenance hemodialysis patients. Methods One hundred and ten hemodialysis patients using AVF more than 3 months were randomly divided into 2 groups, the intervention group (n=55, received aspirin 100 mg/d ) and the control group (n=55). Examinations were performed at baseline and 6-month after treatment. Serum hsCRP level, platelet aggregates ratio(PAR), coagulation and inflammation indicators were measured. AVF embolism and the adverse events were monitored. Results Six months later, PAR and hsCRP level of the intervention group patients aged ≤60 years decreased significantly [(68.14±8.45) % vs (82.37±9.12) %; (4.79±4.81) mg/L vs (6.94±10.26) mg/L, all P<0.05], and were significantly lower as compared to the control group [(68.14±8.45) % vs (74.7±11.50) %, (4.79±4.81) mg/L vs (5.12±9.25) mg/L, all P<0.05]. There were 2 cases of AVF embolism occured in both groups, which showed no statistical difference (P=0.676). The incidence of adverse effects was higher in the intervention group than that in the control group but no statistical significance was found(20.0% vs 7.2%, P=0.052)，while the mortality rate had no difference between 2 groups (3.6% vs 0, P=0.495). Conclusion Use of aspirin 100 mg/d for 6 months can significantly reduce the serum hsCRP level and PAR in hemodialysis patients under 60-year-old without serious adverse reactions.

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Role of renal progenitor-like tubular cells in the repair of acute renal tubular necrosis

FENG Chun-yue;SHAN Juan-ping;JIANG Xin-xin;Kunlin Jin;LU Ming-xi;YE You-xin

2011, 27(4): 276-281.

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Objective To elucidate the role of renal progenitor-like tubular cells in the repair process after acute tubular necrosis (ATN) induced by ischemia. Methods Rat ATN was developed by clamping left kidney artery for 60 minutes, and bromodeoxyuridine(BrdU), a cell division and proliferation marker, was administrated one hour before rats were sacrificed. Kidneys were isolated at 1, 3, 5, 7, 14, 21, 28 days after injury. The proliferative and apoptotic cells were determined by immunostaining using anti-BrdU, Pax2 (an embryonic renal marker), vimentin (an immature mesenchymal cell marker), and activated caspase-3 (a cell apoptosis marker). Results Cell death was found in tubules at day 1 after ischemia and reperfusion injury. BrdU-positive cells were dramatically increased and reached peak at day 3 after injury. In addition, the number of BrdU positive cells in the contralateral kidney was significantly increased compared to sham operated group. Double immunostaining showed that BrdU-positive cells co-expressed Pax2 or vimentin, but not activated caspase-3. Conclusions Renal progenitor-like tubular cells may play a predominant role in repair process following ATN in rats. They may dedifferentiate, proliferate, and then redifferentiate into mature tubular cells. Growth factors may regulate the repair process.

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Effect of CIP4 on human renal tubular epithelial to mesenchymal transition induced by transforming growth factor β1

BAI Shou-jun;ZHANG Ya-min;ZENG Rui;XU Chu-ou;LIU Li-li;ZHOU Qiao-dan;LI Cai-xia;PEI Guang-chang;GE Shu-wang;XU Gang;LIU Xiao-cheng

2011, 27(4): 282-287.

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Objective To observe the effect of CIP4 (Cdc42 interacting protein 4) on human renal tubular epithelial to mesenchymal transition(EMT) induced by transforming growth factor β1(TGF-β1) and to study the associated mechanism. Methods Human proximal tubular epithelial cells (HK-2 cell line) were cultured with TGF-β1(10 μg/L) for 72 hours. The protein expressions of E-cadherin and α-SMA were measured by Western blotting. One set of siRNA oligos specific for CIP4 and CIP4 construction of the entire coding sequence were designed based on the full CIP4 sequence in GenBank. Then HK-2 cells were transfected with CIP4-siRNA or pcDNA3.1-hCIP4 via lipofactamine 2000. The protein expressions of CIP4, E-cadherin and α-SMA were evaluated respectively in control cells, TGF-β1 treated cells, siRNA transfected cells, pcDNA3.1-hCIP4-transfected cells by Western blotting. The distribution of E-cadherin and α-SMA was observed by confocal microscope. After TGF-β1-treated HK-2 cells were interferenced with specific inhibitor of PI3K-Akt (wortmannin) 1 μmol/L for 48 hours, Western blotting was used to detect the CIP4 protein in control cells and interferenced cells. Results With TGF-β1 stimulation, the expression of E-cadherin protein was decreased markedly(P<0.05), and in contract, the expression of α-SMA were increased notably (P<0.05), which revealed that TGF-β1 could induce EMT. After transfected with CIP4-siRNA, the protein expression of E-cadherin was increased (P<0.05), and the protein expression of α-SMA was decreased (P<0.05). The EMT induced by TGF-β1 was effectively reversed. After transfected with pcDNA3.1-hCIP4, the expression of E-cadherin protein was down-regulated (P<0.05), and the expression of α-SMA protein was up-regulated compared with control group (P<0.05), leading to EMT. After HK-2 cells were interferenced with wortmannin for 48 hours, the expression of CIP4 was decreased (P<0.05). Conclusion TGF-β1 up-regulates the expression of CIP4 via PI3K-Akt pathway, and CIP4 may participate in EMT induced by TGF-β1.

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Effect of triperygium wilfordii polyglucoside on the podocytes of diabetic nephropathy rats

ZHENG Yun;HAO Li;PAN Meng-shu;DING Nan

2011, 27(4): 288-292.

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Objective To explore the effect of triperygium wilfordii polyglucoside (TWP) on the podocytes of rats with diabetes nephropathy (DN). Methods One hundred SD rats were randomly divided into normal control group (Group A), DN group (Group B), TWP group (Group C). TWP group was divided into 3 subgroups (Ca, Cb, Cc) according to the different doses 4, 8, 16 mg?kg-1?d-1, respectively. Rats in DN group and TWP group were given streptozocin (STZ) by intraperitoneal injection to establish animal model of diabetes. After 12 weeks, 24 h urinary protein excretion rate(UAER), BUN, Scr, white blood cell (WBC), blood glucose (Glu), and kidney weight (KW)/ body weight (BW) were determined. The renal pathological changes were evaluated by HE staining. The structural change of podocytes was observed by transmission electron microscope. The expressions of nephrin and podocin were evaluated by immunofluorescence staining. Results (1)Compared to group A, Scr, BUN, Glu, KW/BW, and UAER were significantly higher (P＜0.05) in group B and group C. Whereas the elevated liver enzymes and the decreased WBC were presented in group Cc (3/20). Compared to group A, the protein expressions of nephrin and podocin in nephridial tissue were lower, and the significant differences of pathomorphology in glomerulus, tubules and podocytes were observed in group B and group C. (2) Compared to group B, KW/BW and UAER were lower in group C (P＜0.01); the protein expressions of nephrin and podocin were higher in nephridial tissue; the pathomorphological improvements were exhibited in glomerulus, tubules and podocytes in group C, paralleled with the increase of TWP dose (P＜0.05 or P＜0.01). Conclusions TWP may exert the protective effect on podocytes in diabetic nephropathy rats, dependent on the dose of TWP. The mechanism may be associated with the up-regulatied expressions of nephrin and podocin.

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Impact of megsin gene transfection on the expression of extracellular signal-regulated protein kinase under high concentration of glucose

WANG Bao-xing;LI Ying;GUO Dong-hua;SHI Yong-hong;CHI Yan-qing;LIU Mao-dong

2011, 27(4): 293-298.

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Objective To observe the effects of megsin gene transfection on glomerular mesangial cells(GMCs) and the expression of platelet-derived growth factor-BB(PDGF-BB), phosphorylated extracellular signal-regulated protein kinase(pERK1/2), transforming growth factor β1(TGF-β1) and type Ⅳ collagen under high concentration of glucose, and to investigate the impact of megsin gene transfection on the extracellular signal-regulated protein kinase (ERK) siginal pathway. Methods Cultured mesangial cells were divided into seven groups: low glucose group（group A, 5.5 mmol/L）, high glucose group（group B, 30 mmol/L）, high glucose plus empty vector group (group C), high glucose plus megsin expression plasmid group (group D), high glucose plus megsin expression plasmids plus U0126 group(group E), high glucose plus megsin siRNA expression plasmids group(group F) and low glucose plus mannitol(24.5 mmol/L，group G). The expressions of megsin, PDGF-BB, pERK1/2, TGF-β1, as well as type Ⅳ collagen in GMCs of each group were detected by Western blotting, after being cultured for 12, 24 and 48 hours respectively. The concentration of type Ⅳ collagen in cell supernatant was measured by radioimmunochemistry. Results Compared with group A, the expression of megsin was increased in GMCs under high glucose medium, with an increase of PDGF-BB, pERK1/2, TGF-β1 in GMCs and type Ⅳ collagen in the supernatants (P＜0.05, respectively）. The expression of above indices was in time-dependant manner. The over expression of megsin in exposure to high up-regulated the expression of PDGF-BB, pERK1/2, TGF-β1 and type Ⅳ collagen(P＜0.05, respectively). Compared with group D, the application of U0126 (pERK1/2 inhibitor) had no significant effect on the expression of megsin and PDGF-BB(P＞0.05, respectively）. However, the expression of pERK 1/2, TGF-β1 and type Ⅳ collagen were obviously decreased(P＜0.05, respectively). Dowa-regulated expression of megsin by siRNA transfection decreased the expression of PDGF-BB, pERK1/2, TGF-β1 and type Ⅳ collagen(all P＜0.05). Conclusions The expression of megsin and PDGF-BB in GMCs with transfected megsin gene in high glucose medium is increased, possibly in a way of activating ERK signal pathway to some extent that boosts both the expression of TGF-β1 and the production of type Ⅳ collagen. The transfection of megsin siRNA inhibits the expression of obove indices, which probably contributes to the development of diabetic nephropathy.

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血液净化专题

临床研究

基础研究

血液净化专题

临床研究

基础研究