Background::Erythropoietin is a glycoprotein that mainly regulates erythropoiesis. In patients with chronic renal failure with anemia, darbepoetin alfa can stimulate erythropoiesis, correct anemia, and maintain hemoglobin levels. This study was designed to demonstrate the efficacy and safety of darbepoetin alfa injections as being not inferior to epoetin alfa injections (Recombinant Human Erythropoietin injection, rHuEPO) when maintaining hemoglobin (Hb) levels within the target range (10.0-12.0 g/dL) for the treatment of renal anemia.Methods::Ninety-five patients were enrolled in this study from April 15, 2013 to April 10, 2014 at 25 sites. In this study, patients ( n = 95) aged 18-70 years were randomized into a once per week intravenous darbepoetin alfa group ( n = 56) and a twice or three times per week intravenous epoetin alfa group ( n = 39) for 28 weeks, who had anemia with hemoglobin levels between 6 g/dL and 10 g/dL due to chronic kidney disease (CKD) and were undergoing hemodialysis or hemofiltration with ESA-naive (erythropoiesis stimulating agent-naive). The primary efficacy profile was the mean Hb level (the non-inferiority margin was -1.0 g/dL, week 21-28); the secondary efficacy profiles were the Hb increase rate (week 0-4), the target Hb achievement cumulative rate and time, the change trends of the Hb levels, and the target Hb maintenance ratio. Adverse events (AEs) were observed and compared, and the efficacy and safety were analyzed between the two treatment groups. Additionally, the frequencies of dose adjustments between the darbepoetin alfa and epoetin alfa groups were compared during the treatment period. SAS? software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. Results::The mean Hb level was 11.3 g/dL in the darbepoetin alfa group and 10.7 g/dL in the epoetin alfa group, respectively; the difference of the lower limits of the 95% confidence intervals (CI) between the two groups was 0.1 g/dL (>-1.0 g/dL), and non-inferiority was proven; the Hb levels started to increase in the first four weeks at a similar increase rate; no obvious differences were observed between the groups in the target Hb achievement cumulative rates, and the Hb levels as well as the target Hb level maintenance rate changed over time. The incidence of AEs was 62.5% in the darbepoetin alfa group and 76.9% in the epoetin alfa group. All the adverse events observed in the study were those commonly associated with hemodialysis.Conclusion::Darbepoetin alfa intravenously once per week can effectively increase Hb levels and maintain the target Hb levels well, which makes it not inferior to epoetin alfa intravenously twice or three times per week. Darbepoetin alfa shows an efficacy and safety comparable to epoetin alfa for the treatment of renal anemia.

Background::This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection (recombinant human erythropoietin injection, rHuEPO) for the treatment of anemia associated with chronic kidney failure in Chinese patients undergoing hemodialysis.Method::This study was a multicenter, randomized, open-label, intergroup parallel control phase III noninferiority trial from April 19, 2013 to September 9, 2014 at 25 sites. In this study, the members of the darbepoetin alfa group underwent intravenous administration once per week or once every two weeks. The members of the control drug epoetin alfa group underwent intravenous administration two or three times per week. All subjects underwent epoetin alfa administration during the 8-week baseline period. After that, subjects were randomly assigned to the darbepoetin alfa group or epoetin alfa group. The noninferiority in the changes of the average Hb concentrations from the baseline to the end of the evaluation period (noninferiority threshold: -1.0 g/dl) was tested between the two treatments. The time-dependent hemoglobin (Hb) concentration and the maintenance rate of the target Hb concentration (the proportion of subjects with Hb concentrations between 10.0 and 12.0 g/dl) were also evaluated. Iron metabolism, including changes in the serum iron, total iron-binding capacity, ferritin, transferrin saturation, and comparisons of the dose adjustments between the two groups during the treatment period were analyzed further. Adverse events (AEs) were also observed and compared, and the safety was analyzed between the two treatment groups. The conversion rate switching from epoetin alfa to darbepoetin alfa was also discussed. SAS ? software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. Results::Four hundred and sixty-six patients were enrolled in this study, and ultimately 384 cases were analyzed for safety, including 267 cases in the darbepoetin alfa group and 117 cases in the epoetin alfa group. There were 211 cases in the per-protocol set, including 152 cases in the darbepoetin alfa group and 59 cases in the epoetin alfa group. The changes in the average Hb concentrations from the baseline to the end of the evaluation period were -0.07 and -0.15 g/dl in the darbepoetin alfa group and epoetin alfa group respectively. The difference between the two groups was 0.08 g/dl (95% confidence interval [CI]: -0.22 to 0.39), and the lower limit of the 95% CI was -0.22 > -1.0 g/dl. The average Hb concentrations of the two groups were 10.88-11.43 g/dl (darbepoetin alfa) and 10.91-11.38 g/dl (epoetin alfa) during the study period of Weeks 0-28, with the maintenance rates of the target Hb concentration ranging within 71%-87% and 78%-95% in the darbepoetin alfa group and epoetin alfa group respectively. During the period of comparison between the two groups, the incidence of AEs in the darbepoetin alfa group was 61.42%, while in the epoetin alfa group it was 56.41%. All of the adverse events and reactions in the study were those commonly associated with hemodialysis.Conclusion::The overall efficacy and safety of darbepoetin alfa for the treatment of Chinese renal anemia patients undergoing hemodialysis are consistent with those of epoetin alfa.

Background::Erythropoietin is a glycoprotein that mainly regulates erythropoiesis. In patients with chronic renal failure with anemia, darbepoetin alfa can stimulate erythropoiesis, correct anemia, and maintain hemoglobin levels. This study was designed to demonstrate the efficacy and safety of darbepoetin alfa injections as being not inferior to epoetin alfa injections (Recombinant Human Erythropoietin injection, rHuEPO) when maintaining hemoglobin (Hb) levels within the target range (10.0-12.0 g/dL) for the treatment of renal anemia.Methods::Ninety-five patients were enrolled in this study from April 15, 2013 to April 10, 2014 at 25 sites. In this study, patients ( n = 95) aged 18-70 years were randomized into a once per week intravenous darbepoetin alfa group ( n = 56) and a twice or three times per week intravenous epoetin alfa group ( n = 39) for 28 weeks, who had anemia with hemoglobin levels between 6 g/dL and 10 g/dL due to chronic kidney disease (CKD) and were undergoing hemodialysis or hemofiltration with ESA-naive (erythropoiesis stimulating agent-naive). The primary efficacy profile was the mean Hb level (the non-inferiority margin was -1.0 g/dL, week 21-28); the secondary efficacy profiles were the Hb increase rate (week 0-4), the target Hb achievement cumulative rate and time, the change trends of the Hb levels, and the target Hb maintenance ratio. Adverse events (AEs) were observed and compared, and the efficacy and safety were analyzed between the two treatment groups. Additionally, the frequencies of dose adjustments between the darbepoetin alfa and epoetin alfa groups were compared during the treatment period. SAS? software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. Results::The mean Hb level was 11.3 g/dL in the darbepoetin alfa group and 10.7 g/dL in the epoetin alfa group, respectively; the difference of the lower limits of the 95% confidence intervals (CI) between the two groups was 0.1 g/dL (>-1.0 g/dL), and non-inferiority was proven; the Hb levels started to increase in the first four weeks at a similar increase rate; no obvious differences were observed between the groups in the target Hb achievement cumulative rates, and the Hb levels as well as the target Hb level maintenance rate changed over time. The incidence of AEs was 62.5% in the darbepoetin alfa group and 76.9% in the epoetin alfa group. All the adverse events observed in the study were those commonly associated with hemodialysis.Conclusion::Darbepoetin alfa intravenously once per week can effectively increase Hb levels and maintain the target Hb levels well, which makes it not inferior to epoetin alfa intravenously twice or three times per week. Darbepoetin alfa shows an efficacy and safety comparable to epoetin alfa for the treatment of renal anemia.

Background::This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection (recombinant human erythropoietin injection, rHuEPO) for the treatment of anemia associated with chronic kidney failure in Chinese patients undergoing hemodialysis.Method::This study was a multicenter, randomized, open-label, intergroup parallel control phase III noninferiority trial from April 19, 2013 to September 9, 2014 at 25 sites. In this study, the members of the darbepoetin alfa group underwent intravenous administration once per week or once every two weeks. The members of the control drug epoetin alfa group underwent intravenous administration two or three times per week. All subjects underwent epoetin alfa administration during the 8-week baseline period. After that, subjects were randomly assigned to the darbepoetin alfa group or epoetin alfa group. The noninferiority in the changes of the average Hb concentrations from the baseline to the end of the evaluation period (noninferiority threshold: -1.0 g/dl) was tested between the two treatments. The time-dependent hemoglobin (Hb) concentration and the maintenance rate of the target Hb concentration (the proportion of subjects with Hb concentrations between 10.0 and 12.0 g/dl) were also evaluated. Iron metabolism, including changes in the serum iron, total iron-binding capacity, ferritin, transferrin saturation, and comparisons of the dose adjustments between the two groups during the treatment period were analyzed further. Adverse events (AEs) were also observed and compared, and the safety was analyzed between the two treatment groups. The conversion rate switching from epoetin alfa to darbepoetin alfa was also discussed. SAS ? software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. Results::Four hundred and sixty-six patients were enrolled in this study, and ultimately 384 cases were analyzed for safety, including 267 cases in the darbepoetin alfa group and 117 cases in the epoetin alfa group. There were 211 cases in the per-protocol set, including 152 cases in the darbepoetin alfa group and 59 cases in the epoetin alfa group. The changes in the average Hb concentrations from the baseline to the end of the evaluation period were -0.07 and -0.15 g/dl in the darbepoetin alfa group and epoetin alfa group respectively. The difference between the two groups was 0.08 g/dl (95% confidence interval [CI]: -0.22 to 0.39), and the lower limit of the 95% CI was -0.22 > -1.0 g/dl. The average Hb concentrations of the two groups were 10.88-11.43 g/dl (darbepoetin alfa) and 10.91-11.38 g/dl (epoetin alfa) during the study period of Weeks 0-28, with the maintenance rates of the target Hb concentration ranging within 71%-87% and 78%-95% in the darbepoetin alfa group and epoetin alfa group respectively. During the period of comparison between the two groups, the incidence of AEs in the darbepoetin alfa group was 61.42%, while in the epoetin alfa group it was 56.41%. All of the adverse events and reactions in the study were those commonly associated with hemodialysis.Conclusion::The overall efficacy and safety of darbepoetin alfa for the treatment of Chinese renal anemia patients undergoing hemodialysis are consistent with those of epoetin alfa.

Objective To assess the efficacy and safety of ultrasound-guided percutaneous transluminal angioplasty (PTA) for treatment of stenosis of autogenous arteriovenous fistulas in maintenance hemdialysis patients. Methods From September 2016 to August 2017, thirty patients with autologous arteriovenous fistula (AVF) stenosis diagnosed in Guangzhou First People′s Hospital underwent PTA under the guidance of ultrasound for the first time. The vascular diameter of AVF stenosis and the blood flow of AVF before and after operation were evaluated. During the follow-up period,the patency time and complications were recorded. Results In 93. 3%( 28/30) patients, primary ultrasound-guided PTA procedures were successfully performed. The internal diameter of the stenosis increased from (1. 62±0. 30) mm preoperatively to (3. 61±0. 66) mm postoperatively (t＝18. 205,P＜0. 001),and the natural blood flow increased from (270. 0±36. 5) ml/min preoperatively to (611. 4±46. 6) ml/min postoperatively (t＝50. 221,P＜0. 001). The post-intervention primary patency rates at 90 and 180 d were 96. 4%(27/28) and 85. 7%(24/28), respectively. There was no rupture of the vein,or other severe complication during the PTA procedure. One patient had perilesional swelling,and one patient had extravasation after the PTA procedure. Conclusion Ultrasound-guided PTA is a safe and effective method for treatment of stenosis of autogenous arteriovenous fistulas in maintenance hemdialysis patients.

Objective To assess the efficacy and safety of tacrolimus combined with prednisone for treat-ment of refractory idiopathic membranous nephropathy(IMN)patients whose serum anti-phospholipase A2receptor (PLA2R)antibody titers were persistent high. Methods An open prospective study of 12 refractory IMN patients was performed in Guangzhou First People's Hospital between June of 2012 and June 2016.The 12 patients failed to re-spond after a standard course of 6 months in a conventional immunosuppressive therapy(cyclophosphamide,myco-phenolate mofetil or cyclosporine A)combined with prednisone and the patients'serum anti-PLA2R antibody titers were persistent high. They were divided into two groups:The tacrolimus group received tacrolimus combined with prednisone for 12 months and the control group received the same or another conventional immunosuppressive therapy for 6 months.Results At the end of the sixth month after enrollment,proteinuria and serum albumin levels in the ta-crolimus group were significantly improved as compared with those in the control group(P<0.01),and eGFR was higher in the tacrolimus group than in the control group(P<0.05).Severe proteinuria and hypoalbuminemia still re-mained in the control group,and eGFR in the control group declined significantly prior to enrollment(P<0.01).Af-ter 6-month treatment,none of the control group became negative for serum anti-PLA2R antibody,and achieved clini-cal remission. Five patients(83.3%)in the tacrolimus group became negative for serum anti-PLA2R antibody and achieved clinical remission(complete remission in two patients and partial remission in three).After 12-month treat-ment,complete remission was achieved in four patients(66.7%)in the tacrolimus group.Conclusions Persistent high serum anti-PLA2R antibody titers may be a cause of no response to a conventional immunosuppressive therapy in refractory IMN patients.For these patients,tacrolimus combined with prednisone may be an effective alternative treat-ment for disappearance of anti-PLA2R antibody and remission.

Objective To assess the efficacy of mycophenolate mofetil (MMF) combined with prednisone in the treatment of idiopathic membranous nephropathy (IMN) patients with positive serum phospholipase A2 receptor (PLA2R) antibody.Methods An open prospective study was performed on twenty-four biopsy-proven IMN patients with positive serum PLA2R antibody in Guangzhou First People''s Hospital from June 2012 to June 2016.The 24 patients were divided into two groups: MMF group in which MMF combined with prednisone was given for 12 months and CTX group in which intravenous cyclophosphamide (CTX) was monthly given combined with oral prednisone.Results After 6 months of immunosuppressive therapy,complete remission and partial remission rates were 25.0% vs.16.7% and 25.0% vs.25.0% in the MMF group and CTX group,respectively (P>0.05).In the MMF group and CTX group,serum PLA2R antibody in the same amount (8/12,66.7%) of patients turned negative.At the end of twelve-month treatment,all patients with negative PLA2R antibodies achieved complete or partial remission.Clinical remission (including complete and partial remission) rates in the MMF group and CTX group were both 66.7%.After immunosuppressive therapy,the levels of proteinuria and serum albumin in the two groups were significantly improved,but no significant difference were found between the two groups (proteinuria:F within-grouP=98.688,P<0.01;F between-grouP=0.133,P=0.719;F cross-grouP=1.223,P=0.304;serum albumin:F within-grouP=30.629,P<0.01;F between-grouP=0.137,P=0.715;F cros-grouP=0.455,P=0.565).At the end of six and twelve months of treatment,the proteinuria (after six months,MMF group: (2 893±2 515) mg/g vs.(6 236±2 117) mg/g,t=-3.522,P=0.002;CTX group: (2 690±2 254) mg/g vs.(5 386±2 447) mg/g,t=-2.808,P=0.010;after twelve months,MMF group:1 025(99-4 635) mg/g vs.(6 236±2 117) mg/g,Z=-3.291,P<0.0005;CTX group: (775(41-3 517) mg/g vs.(5 386±2 447) mg/g,Z=-3.118,P=0.001) and serum albumin levels (after six months,MMF group: (28.5±9.7) g/L vs.(19.8±4.4) g/L,t=2.841,P=0.012;CTX group: (29.0±7.6) g/L vs.(22.3±4.1) g/L,t=2.690,P=0.016;at the end of twelve months of treatment,,MMF group: (32.4±8.5) g/L vs.(19.8±4.4) g/L,t=4.570,P<0.0005;TX group: (32.2±7.9) g/L vs.(22.3±4.1) g/L,t=3.862,P=0.001) of the two groups were better than those prior to treatment.Conclusion For the IMN patients with positive serum PLA2R antibody,MMF combined with prednisone was as effective as conventional CTX combined with prednisone in the negative conversion of PLA2R antibody and the remission.The negative conversion of PLA2R antibody after 6 months of immunosuppressive treatment was an important indicator of predicting the remission.

Objective To investigate the role of miR-155 in diabetic nephropathy(DN)and its mecha-nism. Methods MiR-155 expression level in kidney was detected by real-time PCR and in situ hybridization. The target gene of miR-155 was predicted by bioinformatics and verified by Western Blot and double luciferase reporter activity. Western Blot was used to detect the related marker proteins of mesangial cells proliferation and mesangial matrix. Results (1)The expression of miR-155 increased in DN renal tissue and high glucose-stimulated renal cells.(2)MiR-155 was related to the regulation of Smad5 gene expression.(3)MiR-155 promoted the mesangial cells proliferation and increased extracellular matrix by down-regulating Smad5 expression. Conclusions MiR-155 can promote the mesangial cells proliferation and renal fibrosis by regulating Smad5 gene,providing a basis for further understanding the pathogenesis of DN.

Objective To evaluate whether three chronic kidney disease epidemiology collaboration (CKD-EPI) equations (CKD-EPI2009Scr,CKD-EPI2012SCysC and CKD-EPI2012Scr-SCysC) are applicable in the prediction of glomerular filtration rate (GFR) in Chinese patients with diabetic nephropathy (DN).Methods One hundred and eight patients with DN who were hospitalized in the First Affiliated Hospital of Guangzhou Medical University with GFR being measured by dynamic renal imaging with 99mTc-DTPA from June 2012 to April 2014 were enrolled in this study.GFR measured by dynamic renal imaging with 99mTe-DTPA was used as the reference value (rGFR).GFR was estimated by the CKD-EPI2009Scr equation,the CKD-EPI2012SCySC equation,and the CKD-EPI2012Scr-SCysC equation (labeled as eGFR1,eGFR2,eGFR3).The correlation,30％ accuracy,staging consistency,deviation and diagnostic accuracy were compared among the three CKD-EPI equations.Results The rGFR in 108 DN patients was (61.78±26.51) ml· min-1· (1.73 m2)-1.The correlation between three eGFRs and rGFR was significant (all P ＜ 0.01),the correlation coefficients were 0.738,0.708,0.782.The 30％ accuracy were 74.07％,52.78％,67.59％,The 30％ accuracy of eGFR1 and eGFR3 were higher than eGFR2 (all P ＜ 0.05),but there was no significant difference between eGFR3 and eGFR1 (x2=0.874,P=0.436).The staging consistency was not ideal,Kappa values were 0.391,0.180 and 0.422.For the deviations between three eGFRs and rGFR,there was no significant difference between eGFR3 and rGFR (P ＞ 0.05),eGFR1 underestimated rGFR,eGFR2 overestimated rGFR (all P ＜ 0.01).The results of the Bland-Altman chart showed that consistencies between three eGFRs and rGFR were poor,the degree of deviation of eGFR3 was the smallest.The area under the ROC curve (AUC) of three eGFRs was 0.878,0.883 and 0.915.The AUC,sensitivity,specificity,overall compliance rate and Youden index of eGFR3 were the highest.Conclusions The eGFRs predicted by the three CKD-EPI equations showed good relevance,accuracy and diagnostic accuracy with the rGFR,but poor in consistencies.Comparatively,CKD-EPI2012Scr-SCysC may be better than others,but its consistency limits exceeds the acceptable limits.Therefore,the applicability of using the three CKD-EPI equations to predict the GFR in Chinese DN patients requires a larger sample and multiple verifications as well as further improvement.

Objective To investigate the effect of losartan on tubulointerstitial fibrosis of rat unilateral ureteral obstruction(UUO) model, and to study whether the use of large dose could be better exert a superior renoprotective effect than conventional dose. Methods Three days after UUO, rats were randomly assigned to conventional dose and large dose of losartan group, shamoperated group and operation group. Two treatment groups were administered orally with a daily dose of losartan 50 mg/kg or 500 mg/kg by gastric gavage. Sham-operated group and operation group received the same volume of physiological saline. Rats were sacrificed 7, 14, 21 days after obstruction. Daily urinary albumin excretion(UalbV), tail-cuff pressure(TCP), the percentage of renal tubular lesions, fractional interstitial area (INT), macrophage infiltration and the expression of transforming growth factor (TGF)-β1 mRNA were assessed and compared. Results The TCP, UalbV, percentage of tubular lesions and interstitial fibrosis, the number of interstitial macrophages and the expression of TGF-β1 mRNA were significantly increased in operation group as compared with other groups (P<0.05). Furthermore, in comparison with conventional dose, the large dose treatment significantly reduced TCP and UalbV, attenuated interstitial fibrosis and tubular lesions, suppressed macrophages infiltration and the expression of TGF-β1 mRNA. Conclusion The large dose of losartan provides superior renoprotection compared to the treatment with conventional dose in UUO model, which interrupts the positive feedback involved in the vicious cycle between inflammatory cell and Ang Ⅱ.