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Correlation of serum hepcidin with residual renal function and micro-inflammation in peritoneal dialysis patients

Zhihong FENG ; Xiaoling ZHOU ; Menghua CHEN

Chinese Journal of Nephrology.2014;30(10):739-743. doi:10.3760/cma.j.issn.1001-7097.2014.10.003

Objective To study the correlation of serum hepcidin with residual renal function and micro-inflammation state in continuous ambulatory peritoneal dialysis (CAPD) patients.Methods Thirty-four stable CADP patients were involved in this study as observers (CAPD group),who had accepted CAPD treatment more than three months; twenty non-dialysis patients with stage 5 of chronic kidney disease were selected as control group.According to the level of high sensitivity Creactive protein (hs-CRP),CAPD patients were divided into two subgroups.There were 14 patients in the hsCRP elevated group (hs-CRP ＞ 3.00 mg/L) and 20 patients in the hs-CRP normal group.In addition,there had been 14 patients with residual renal function in CAPD group.Serum hepcidin was measured by ELISA.Serum Ferritin (FER),hs-CRP,routine blood and biochemistry were measured by routine methods.Calculated estimated glomerular filtration rate (eGFR).Pearson correlation and linear regression were used to assess the correlation of serum hepcidin with other laboratory parameters in CAPD patients.Results (1) Serum hepcidin was significantly higher in CAPD patients than control group,but eGFR was significantly lower (P ＜ 0.01).(2) Serum hepcidin levels of no residual renal function patients increased more significantly in CAPD group (P ＜ 0.05).(3) Serum hepcidin levels were higher in hs-CRP elevated group than hs-CRP normal group (P ＜ 0.05).(4) Pearson correlation analyses revealed that serum hepcidin was positively correlated with hs-CRP (r=0.501) and FER (r=0.847,all P ＜ 0.01),and was negatively correlated with Hb (r=-0.919),TRF (r=-0.751),TIBC (r=-0.532,all P ＜ 0.05).(5) Multiple linear regression analysis showed that ferritin and hs-CRP were closely associated with serum hepcidin level in CAPD.Conclusions Serum hepcidin level markedly elevate in CAPD patients,especially in the patients with no residual renal function and micro inflammatory state increased more significantly.

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Role of β-catenin signaling pathway in the epithelial to mesenchymal transition induced by parathyroid hormone in renal tubular epithelial cells

Yunshan GUO ; Aiping ZHANG ; Yanxia WANG ; Lei ZHANG ; Hongdong LI ; Zhen LI ; Yaohai DING

Chinese Journal of Nephrology.2014;30(10):763-769. doi:10.3760/cma.j.issn.1001-7097.2014.10.007

Objective To investigate the effect of parathyroid hormone (PTH) on the epithelial to mesenchymal transition (EMT) in human renal proximal tubular epithelial cells (HK-2 cells),and determine the role of β-catenin signaling pathway.Method The expression of α-smooth muscle actin (α-SMA),E-cadherin and β-catenin in HK-2 cells was measured by real-time PCR,Western blotting and immunofluorescence technique.The signaling pathway by which PTH activated EMT in HK -2 cells was identified by using synthetic β-catenin siRNA.Results Parathyroid hormone (10-10mol/ L) increased α-SMA expression and decreased E-cadherin expression in HK-2 cells (P＜ 0.01,respectively).Untreated cells showed the expression of E-cadherin,whereas α-SMA staining was noticeably increased in cells treated with PTH.β-catenin activity was significantly increased after exposed to PTH.Theα-SMA expression was decreased strongly and E-cadherin expression was increased after β-catenin siRNA transfection (all P ＜ 0.05).Conclusion PTH significantly induces epithelial to mesenchymal transition in HK-2 cells throughβ-catenin signaling pathway.

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The effects of calcitriol on ameliorating podocytes impairment and its possible mechanism in DN rats

Zhixia SONG ; Yinfeng GUO ; Min ZHOU ; Xiaoliang ZHANG

Chinese Journal of Nephrology.2014;30(10):777-783. doi:10.3760/cma.j.issn.1001-7097.2014.10.009

Objective To investigate the effects and underlying mechanism of calcitriol on ameliorating podocytes impairment in DN rats.Methods SD rats were randomly divided into four groups:normal control (NC) group,calcitriol treatment (VD) group:calcitriol 0.1μg· kg--1 d-1,diabetic nephropathy (DN) group:streptozocin (STZ) 58 mg/kg,DN treated with calcitriol (DN + VD) group:calcitriol 0.1 μg · kg-1 · d-1 + STZ 58 mg/kg.Rats were sacrificed at the end of 18 weeks.Results Compared with the DN group,the DN + VD group exhibited significantly lower proteinuria by 36％,improved renal histology at the end of the experiment (P ＜ 0.05),and similar levels of blood glucose,serum urea nitrogen as well as body weight (P ＞ 0.05).There were no significant differences in the serum concentrations of creatinine,calcium and phosphorus among the four groups (P ＞ 0.05).In DN group,the expressions of nephrin,podocin,VDR,PI3K-p85 and p-Akt were significantly decreased and the expression of desmin was increased compared to NC group.Calcitriol treatment could attenuate the above changes.Additionally,a positive correlation was observed between the expressions of nephrin and VDR (r=0.776,P ＜ 0.05).Likewise,the expression of nephrin was positively correlated with either PI3K -p85 or p-Akt (r=-0.736,r=0.855,all P ＜ 0.05).Conclusion Calcitriol can ameliorate podocytes injury in DN rats,which might be related with the further up-regulation of PI3K/p-Akt signaling pathway.

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Meta analysis for the long-term efficacy and safety of immunosuppression on the progression of IgA nephropathy

Lei TIAN ; Xinghua SHAO ; Yuanyuan XIE ; Qin WANG ; Ling WANG ; Zhaohui NI ; Shan MOU

Chinese Journal of Nephrology.2014;30(11):833-840. doi:10.3760/cma.j.issn.1001-7097.2014.11.005

Objective To access the long-term efficacy and safety of immunosuppression on the progression of IgA nephropathy (IgAN) by Meta analysis.Methods Databases EMBASE,Pubmed,Elsevier Science Direct,Scopus,Web of Science,Google Scholar,Cochrane Library,China National Knowledge Infrastructure,WanFang and VIP Data were retrieved to collect the randomized controlled trials (RCTs) at least 3 years follow-up on immunosuppression for IgAN published before May 2014.The literatures were screened independently by two reviewers according to the inclusion and exclusion criteria,and the methodological quality was assessed.Statistic software Stata 12.0 was used to conduct analysis.Results Nine articles were included in this study with a total of 568 patients.Immurnosuppression could lowered the risk for the progression to ESRD (RR=0.32,95％CI:0.20-0.49,P ＜ 0.01).As far as the efficacy of immunosuppression,subgroup analysis indicated that three studies with more than 7 year follow-up (RR=0.28,95％CI:0.13-0.59,P ＜ 0.01) were similar with 7 studies followed by for less than 7 years (RR=0.34,95％ CI:0.19-0.59,P＜0.01); six adopted immunosuppressor monotherapy (RR=0.29,95％ CI:0.15-0.58,P＜ 0.01) were similar to two used corticosteroids plus other immunosuppression (RR=0.33,95％CI:0.18-0.59,P ＜ 0.01); There were no significant differences between four studies from Europe (RR=0.27,95％CI:0.14-0.53,P ＜ 0.01) and five from Asia (RR=0.35,95％ CI:0.19-0.65,P＜0.01).Immunosuppression was associated with an increased risk for adverse events (RR=2.33,95％ CI:1.33-4.09,P＜0.01).Conclusion Immunosuppression for IgAN may reduce long-term risk of progression to ESRD,but increase the risk of adverse events to some extent.

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Clinical analysis of 1 371 patients with acute kidney injury after acute myocardial infarction

Yanbei SUN ; Bicheng LIU ; Yun ZOU ; Jiarong PAN ; Yuan TAO ; Min YANG

Chinese Journal of Nephrology.2014;30(10):725-731. doi:10.3760/cma.j.issn.1001-7097.2014.10.001

Objective To investigate the risk factors of acute kidney injury (AKI) in patients after acute myocardial infarction (AMI).Methods A total of 1 371 adult patients diagnosed AMI in the First People's Hospital of Changzhou from January 2008 to December 2012 were analyzed retrospectively.AKI was defined according to the 2012 KDIGO AKI criteria.Based on the occurrence of AKI,the patients were divided into AKI group and non-AKI group.According to the AKI timing,the patients were divided into subgroups including conservative treatment groups,coronary angiography (CAG) groups and coronary artery bypass grafting (CABG) groups,respectively.Related risk factors of AKI were analyzed by univariate and multivariate logistic regression.Results Of the 1 371 patients,410(29.9％) developed AKI.Compared to the non-AKI group,in-hospital mortality increased significantly in the AKI group (17.1％ vs 3.9％,x2=68.0,P ＜ 0.001).Multifactor retrospective analysis showed that decreased baseline eGFR (OR=2.049,95％ CI:1.246-3.370),increased fasting plasma glucose(FPG) (OR=1.070,95％CI:1.018-1.124),diuretics (OR=1.867,95％CI:1.220-2.856) and Killip class 4 status (OR=1.362,95％ CI:1.059-3.170) were all independent risk factors of AKI,while increased DBP on admission was a protective factor (OR=0.986,95％ CI:0.974-0.998) for the conservative management group.Decreased baseline eGFR (OR=2.371,95％CI:1.500-3.747),increased FPG(OR=1.009,95％CI:1.005-1.012),diuretics (OR=1.674,95％CI:1.042-2.690),intraoperative hypotension (OR=2.276,95％ CI:1.324-3.575) and acute infection (OR=1.678,95％CI:1.023-2.754) were independent risk factors of AKI for the CAG group.Decreased baseline eGFR (OR=2.246,95％CI:1.340-3.981),increased FPG (OR=1.059,95％CI:1.018-1.124),diuretics (OR=1.723,95％CI:1.122-2.650),and low cardiac output syndrome after operation (OR=2.331,95％ CI:1.277-3.286) were independent risk factors of AKI for CABG group.Conclusions AKI is a common complication and associated with increased mortality after AMI.Decreased baseline renal function,increased FPG and diuretics were common independent risk factors of AKI after AMI.

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Rapamycin reduces podocyte adhesion damage caused by sublytic C5b-9 via autophagy activation

Qianying LYU ; Jianhua ZHOU ; Yu CHEN ; Fengjie YANG ; Jinyun PU ; Yu ZHANG

Chinese Journal of Nephrology.2014;30(10):751-756. doi:10.3760/cma.j.issn.1001-7097.2014.10.005

Objective To determine the effect of rapamycin on sublytic C5b-9-induced podocyte adhesion damage,and whether autophagy is involved in this progression.Methods Sublytic complement C5b-9 stimulation was used in vitro.Autophagosomes were viewed using electron microscopy.Western blotting was used to measure the change of autophagy-related markers.Attachment assay was used to assess the adhesion of podocyte.Confocal microscopy was used to explore the expression patterns of cytoskeletal protein F-actin.Flow cytometry was used to measure the level of adhesion-associated protein integrin α3.Results (1) For ensuring sublytic complement injury,the maximal amounts of anti-podocyte antiserum and 160×-diluted normal human serum were used without inducing cell lysis (defined as ＞ 5％ LDH release).(2) Sublytic C5b-9 promoted autophagy in podocyte in vitro.The proautophagic effect of sublytic C5b-9 manifested in the form of accumulated autophagosomes and enhanced expression of LC3-lⅡ.(3) Inhibition of autophagy by 3-methyadenine enhanced the effect of sublytic C5b-9-induced podocyte injury,including serious cytoskeleton damage and markedly reduced adhesion of podocyte.(4) Rapamycin treatment significantly improved the above lesions.(5) Rapamycin enhanced autophagy induced by sublytic C5b-9 in podocyte.Conclusions In summary,rapamycin can improve sublytic CSb-9-induced podocyte adhesion damage by appropriate autophagy activation.These findings provide important information for the development of appropriate protocols for the application of mTOR (mammalian target of rapamycin) inhibitors in podocytopathy.

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Clinical characteristics of malignant tumor patients complicated by acute kidney injury

Xuemei LIU ; Mengchun LIU ; Ruixia MA ; Liqiu LIU ; Yan XU

Chinese Journal of Nephrology.2014;30(11):813-818. doi:10.3760/cma.j.issn.1001-7097.2014.11.002

Objective To analyze the clinical features and prognostic factors of patients with malignant tumor complicated by acute kidney injury (AKI),and provide the basis for preventing AKI and improving the prognosis.Methods Malignant tumor patients complicated by AKI were screened with the electronic medical records system from January 2001 to December 2012 at the Affiliated Hospital of Qingdao University.The clinical characteristics in the 12 years were analyzed by statistical analysis and compared.The risk factors of the hospital mortality in malignancies tumor complicated by AKI were analyzed by Logistic regression analysis.Results A total of 100 patients with malignant tumor complicated by AKI were collected,accounting for 24.94％ of AKI patients and 1.66‰ of malignant tumor patients at the same period.Malignancies were consist of hematologic malignancies (11％),non-metastatic solid tumor (47％),metastatic solid tumor (42％).The most common factor leading to AKI for malignancies was post-renal obstruction (64％),followed by nephrotoxic drugs or contrast agents (24％),hypovolemia (18％).There was no significant change of the etiologies for AKI between the first six-year and the second six-year (P ＞ 0.05).The hospital mortality of patients with malignant tumor complicated by AKI was 25％,and multivariate Logistic regression analysis showed that multiple etiologies (OR=13.356),multiple organ failure (OR=222.256),and metastatic solid tumors (OR=8.497) were the independent risk factors for hospital mortality.Conclusions AKI is a common complication in patients with malignant tumors,and the most common factor leading to AKI is postrenal obstruction.The hospital mortality in malignancies with AKI is high,which should get the attention of clinicians.

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Primary study in maturity status of native arteriovenous fistula on the wrist

Yuankai XU ; Lihong ZHANG ; Wenyun ZHANG ; Qingqing DUAN ; Qiongzhen LIN ; Ying LI

Chinese Journal of Nephrology.2014;30(11):841-845. doi:10.3760/cma.j.issn.1001-7097.2014.11.007

Object To investigate the maturity status of the cephalic vein when the native arteriovenous fistula matures and set up indicators of a matured native arteriovenous fistula.Methods The diameter,flow rate and wall thickness of the cephalic vein were prospectively measured by Doppler ultrasound after the native fistula was created.Mature judgment was done by skilled nurses depending on their experience before the fistula was punctured.The ultrasound data was marked as proposed mature at the same time.After three times dialysis,if blood flow was fluent and complications such as prolonged bleeding time and hematoma were absent,fistula mature was confirmed.Results Thirty-one patients were admitted to the study,then fistula were matured.The average age of those patients was (52.93±3.21) years old.Thirteen patients were female.Twenty two fistula located on the left arm.Thirteen of the patients were diabetic nephropathy.The average diameter of cephalic vein was increased from (3.10±0.11) mm before surgery to (4.74±0.16) mm when the fistula was matured,though it was still smaller than 6 mm which K/DOQI guideline had recommended (P ＜ 0.05).The average mature period was (57.10±3.21) days.The matured fistula had an average high flow rate of (569.76±48.34) ml/min and wall thickness of (0.95±0.04) mm.The one-side 95％ credibility interval of the diameter,flow rate and wall thickness of cephalic vein was 4.44 mm,486.37 ml/min and 0.67 mm,respectively.Conclusions The diameter of cephalic vein in a matured native arteriovenous fistula in our study was significantly smaller than 6 mm which K/DOQI guideline had recommended.The indicators of native arteriovenous fistula mature in our country may different from abroad.

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Tacrolimus in the treatment of HBV associated membranous nephropathy: a randomized controlled trial

Jingfang WAN ; Xiaomei LU ; Xuelian TANG ; Kaibin LI ; Lirong LIN ; Yani HE ; Kailong LI

Chinese Journal of Nephrology.2015;31(1):1-6. doi:10.3760/cma.j.issn.1001-7097.2015.01.001

Objective To conduct a prospective,randomly controlled trial,evaluating the combination of tacrolimus,corticosteroids and entecavir for the treatment of adult patients with biopsyproven hepatitis B virus-associated membrane nephropathy (HBV-MN).Methods A total of 38 patients with biopsy-confirmed HBV-MN were randomized to the tacrolimus group (n=19) and the control group (n=19).Patients in tacrolimus group received combination therapy of tacrolimus (0.05 mg·kg-1 · d-1),corticosteroids (prednisone acetate,0.5 mg· kg-1 · d-1) and entecavir (0.5 mg/d),whereas patients in control group received entecavir mono-therapy (0.5 mg/d).The primary end point was the percentage of patients reaching complete remission (CR) or partial remission (PR).Results The probability of remission in the treatment group was 88.89％ and 94.44％ after 6 and 12 months,but only 38.89％ and 58.82％ in the control group,respectively.The decrease in proteinuria was significantly greater in the treatment group.Entecavir was used for the treatment of hepatitis in all patients,which caused the disappearance of serum hepatitis B viral DNA(HBV-DNA) and the normalization of ALT and AST levels in 3 months.Notably,two patients in the control group and one patient in the treatment group reached the secondary end point.One patient in the tacrolimus-treated group showed a relapse during the taper period.Conclusion This treatment protocol not only can control the replication of HBV-DNA but also can reduce proteinuria and preserve renal function,it is one of useful therapeutic options for patients with HBV-MN.

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Efficacy of paricalcitol on eGFR and proteinuria in non-dialysis CKD patients: a meta-analysis

Yongxin LU ; Shenglin YANG ; Yumin LI ; Min LIANG

Chinese Journal of Nephrology.2015;31(1):30-36. doi:10.3760/cma.j.issn.1001-7097.2015.01.006

Objective To systematic evaluate the efficacy of paricalcitol on estimated glomerular filtration rate (eGFR) and proteinuria in non-dialysis chronic kidney disease (CKD) patients.Methods According to the collaborative search strategy,PubMed,the clinical control test database of Cochrane Library,Embase,Chinese Wanfang database,CNKI,VIP database (form the date of database establishment to March 2014) were searched.Published and unpublished literature,abstracts in academic meetings (ASN,WCN,CSN) were also searched by hand.The randomized controlled trials (RCTs) about the efficacy paricalcitol on eGFR and proteinuria in non-dialysis CKD patients were selected.Review Manager Software 5.2 was used for statistical analysis.Results Seven RCTs with a total of 834 patients were included (508 in experimental group,326 in placebo group).No statistical difference of the efficacy on eGFR[SMD=-0.10,95％ CI:(-0.28-0.07),P=0.26] between lower dose paricalcitol (＜ 2 μg/d) group and placebo group,while higher dose (2 μg/d) group reduced eGFR significantly [SMD=-0.45,95％ CI:(-0.63--0.27),P ＜ 0.01].Compared with placebo,paricalcitol reduced proteinuria significantly [OR(95％C1):2.09(1.52-2.58),P ＜ 0.01],and there was no difference between different dose groups [OR(95％CI):1.09(0.62-1.91),P=0.77].Lower dose group [OR(95％C1):0.93(0.57-1.52),P=0.76] and higher dose group [OR(95％ CI):2.08(0.70-6.18),P=0.19] did not significantly increase the risk of adverse events.Conclusions Lower dose paricalcitol (＜ 2 μg/d)has no effect on eGFR in non-dialysis CKD patients meanwhile reduces proteinuria.The higher dose (2μg/d) may reduce eGFR without farther reduction in proteinuria.

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