***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Continuous erythropoietin receptor activator ( CERA ) seems to maintain a stable hemoglobin ( Hb ) level because its half-life is longer than darbepoetin α ( DA ) . Twenty chronic kidney disease ( CKD ) patients at the pre-dialysis stage who had been administered DA for over 24 weeks were r and omly assigned to receive subcutaneous CERA or DA once every four weeks during 48 weeks . In both groups , the rate of achievement of target Hb level changed from 70 % to 100 % in weeks 0 to 48 , with no significant difference between the groups . Compared with week 0 , the Hb level was significantly increased from week 24 in the DA group and from week 8 in the CERA group . In addition , the reticulocyte count was significantly increased from week 4 in the CERA group compared with the DA group . There was no significant difference in the levels of estimated glomerular filtration rate and iron status between both groups . Because of the small number of patients in this study , only limited conclusions can be drawn . However , the results suggest that subcutaneous administration of DA or CERA once every four weeks to predialysis patients has similar effects on achievement of target Hb levels Background In a simulation based on a pharmacokinetic model we demonstrated that increasing the erythropoiesis stimulating agents ( ESAs ) half-life or shortening their administration interval decreases hemoglobin variability . The benefit of reducing the administration interval was however lessened by the variability induced by more frequent dosage adjustments . The purpose of this study was to analyze the reticulocyte and hemoglobin kinetics and variability under different ESAs and administration intervals in a collective of chronic hemodialysis patients . Methods The study was design ed as an open-label , r and omized , four-period cross-over investigation , including 30 patients under chronic hemodialysis at the regional hospital of Locarno ( Switzerl and ) in February 2010 and lasting 2 years . Four subcutaneous treatment strategies ( C.E.R.A. every 4 weeks Q4W and every 2 weeks Q2W , Darbepoetin alfa Q4W and Q2W ) were compared with each other . The mean square successive difference of hemoglobin , reticulocyte count and ESAs dose was used to quantify variability . We distinguished a short- and a long-term variability based respectively on the weekly and monthly successive difference . Results No difference was found in the mean values of biological parameters ( hemoglobin , reticulocytes , and ferritin ) between the 4 strategies . ESAs type did not affect hemoglobin and reticulocyte variability , but C.E.R.A induced a more sustained reticulocytes response over time and increased the risk of hemoglobin overshooting ( OR 2.7 , p = 0.01 ) . Shortening the administration interval lessened the amplitude of reticulocyte count fluctuations but result ed in more frequent ESAs dose adjustments and in amplified reticulocyte and hemoglobin variability . Q2W administration interval was however more favorable in terms of ESAs dose , allowing a 38 % C.E.R.A. dose reduction , and no increase of Darbepoetin alfa . Conclusions The reticulocyte dynamic was a more sensitive marker of time instability of the hemoglobin response under ESAs therapy . The ESAs administration interval had a greater impact on hemoglobin variability than the ESAs type . The more protracted reticulocyte response induced by C.E.R.A. could explain both , the observed higher risk of overshoot and the significant increase in efficacy when shortening its administration interval . Trial registration Clinical Trials.gov : Background . No previous r and omized controlled studies have been reported examining de novo , once every 4 weeks ( Q4W ) administration of erythropoiesis-stimulating agents in chronic kidney disease ( CKD ) patients . We report results from a r and omized multinational study that compared continuous erythropoietin receptor activator ( C.E.R.A. ) Q4W with darbepoetin alfa once weekly ( QW ) or every 2 weeks ( Q2W ) for the correction of anaemia in non-dialysis CKD patients . Methods . Patients were r and omized ( 1:1 ) to receive either 1.2 μg/kg C.E.R.A. Q4W or darbepoetin alfa QW/Q2W during a 20-week correction period and an 8-week evaluation period . Two primary end points were assessed : the haemoglobin ( Hb ) response rate and the change in average Hb concentration between baseline and evaluation . Results . The Hb response rate for C.E.R.A. was 94.1 % , significantly higher than the protocol -specified 60 % response rate [ 95 % confidence interval ( CI ) : 89.1 , 97.3 ; P < 0.0001 ] and comparable with darbepoetin alfa ( 93.5 % ; 95 % CI : 88.4 , 96.8 ; P < 0.0001 ) . C.E.R.A. Q4W was non-inferior to darbepoetin alfa QW/Q2W , with similar mean Hb changes from baseline of 1.62 g/dL and 1.66 g/dL , respectively . Patients receiving C.E.R.A. showed a steady rise in Hb , with fewer patients above the target range during the first 8 weeks compared with darbepoetin alfa [ 39 patients ( 25.8 % ) versus 72 patients ( 47.7 % ) ; P < 0.0001 ] . Adverse event rates were comparable between the treatment groups . Conclusion . C.E.R.A. Q4W successfully corrects anaemia and maintains stable Hb levels within the recommended target range in non-dialysis CKD patients Background . It is unknown whether early intervention with low‐dose erythropoiesis‐stimulating agents ( ESAs ) in non‐anaemic patients delays progression of chronic kidney disease ( CKD ) . Methods . In a single‐blind , 24‐month trial , adults with estimated glomerular filtration rate ( eGFR ) 30‐59 mL/min/1.73 m2 and either Type 2 diabetes mellitus or previous kidney transplantation were r and omized to low‐dose continuous erythropoiesis receptor activator ( CERA ; monthly dose 30‐75 & mgr;g ; n = 115 ) or placebo ( n = 120 ) . The primary endpoint was the annual change in eGFR ( abbreviated Modification of Diet in Renal Disease formula ) . Results . Mean ( st and ard deviation ) eGFR was 40.7 ( 9.8 ) mL/min/1.73 m2 versus 39.8 ( 9.2 ) mL/min/1.73 m2 at baseline for CERA and placebo , respectively , and 39.0 ( 11.6 ) g/dL versus 39.7 ( 10.6 ) g/dL at the final visit . The median ( interquartile range ) annual reduction in eGFR was 0.5 ( −2.2 , 3.8 ) mL/min/1.73 m2 with CERA versus 0.4 ( −2.0 , 3.2 ) mL/min/1.73 m2 with placebo ( P = 0.657 ) . No significant difference in the annual change in eGFR was observed between treatment groups in the sub population s with Type 2 diabetes or kidney transplant . Adverse events with a suspected relation to study drug occurred in 22.0 % and 16.2 % of patients r and omized to CERA or placebo , respectively , and adverse events led to study drug discontinuation in 11.0 % and 8.5 % of patients . Conclusions . Patients with moderate CKD and Type 2 diabetes or previous kidney transplantation showed stable renal function that was unaffected by administration of low‐dose ESA . In addition , there was no clinical ly meaningful effect of 2‐year low‐dose ESA treatment on albuminuria , an important surrogate marker of kidney injury BACKGROUND Sustained erythropoiesis-stimulating agents ( ESAs ) have recently been identified as the st and ard therapeutic agent for anemia in patients undergoing peritoneal dialysis ( PD ) . However , few reports have compared pain between various types of sustained ESAs or between administration routes . Furthermore , the change ratio of the dose of sustained ESAs reportedly ranges from 0.8 to 1.3 . In the present study , to compare darbepoetin alfa and epoetin beta pegol ( a continuous erythropoietin receptor activator [ CERA ] ) , we examined the dolorific differences between administration routes and the effect on anemia by using a chjange ratio of 0.8 with darbepoetin alfa in patients with renal anemia undergoing PD . SUBJECTS AND METHOD We r and omly assigned 20 patients with stable hemoglobin levels undergoing PD to either a darbepoetin alfa therapy group or a CERA therapy group . Based on a previous report , the change ratio of the CERA group from CERA to darbepoetin alfa therapy was assumed to be 0.8 , and therapy was crossed-over to darbepoetin alfa again 2 months later . The dolorific evaluation ( pain measurement ) used both a face scale and a visual analogue scale . We compared the agents as well as administration routes with respect to pain . We also measured variables related to anemia and iron metabolism . RESULTS The change ratio of the CERA group at the start of the study was 0.821 . On resumption of darbepoetin alfa therapy 2 months later , the doses of darbepoetin alfa  increased . The darbepoetin alfa group showed a stronger tendency for pain , although the difference was not significant . In contrast , subcutaneous administration in the CERA group showed significant pain just after injection . The CERA group , however , showed a significant decrease in hemoglobin levels after 2 months of treatment ( p=0.0489 ) . No significant change was found in the hematocrit or the reticulocyte count . There were no significant differences in iron metabolism , as shown by serum iron levels and total iron-binding capacity , in either group . However , serum ferritin levels showed a tendency to decrease in the darbepoetin alfa group . CONCLUSION No significant difference in pain was found between darbepoetin alfa and CERA therapies , but a significant difference in pain was noted between administration routes , just after injection , in the CERA group . The results also suggest that a change ratio of 0.8 from darbepoetin alfa to CERA is low for managing anemia Continuous erythropoietin receptor activator ( CERA ) is an erythropoietin with a long-half life . This study investigated the efficacy of CERA for correcting anemia in Korean patients on dialysis . Patients ( ≥18 yr ) who were not receiving any ESAs for more than 8 weeks were r and omly assigned to either intravenous CERA once every 2 weeks ( n=39 ) or epoetin beta thrice-weekly ( n=41 ) during a 24-week correction phase . Hemoglobin ( Hb ) response was defined as increase of Hb by at least 1 g/dL and Hb≥11 g/dL without red blood cell ( RBC ) transfusion .  Median dialysis duration was 1.7 ( 0.3 - 20.8 ) and 1.6 ( 0.4 - 13.8 ) yr in CERA and epoetin beta group , respectively . Hemoglobin response rate of CERA was 79.5 % ( 95 % confidence interval [ CI ] , 63.5 - 90.7 ) . As the lower limit of 95 % CI was higher than pre-specified 60 % response rate , it can be concluded that CERA  corrected anemia ( P<0.05 ) . Hb response rate of epoetin beta was 87.8 % ( 95 % CI , 73.8 - 95.9 ) ( P=0.37 ) . Median time to response was 12 weeks in CERA and 10.3 weeks in epoetin beta ( P=0.03 ) . It is suggested that once every 2 weeks administration of CERA is effective for correcting anemia in Korean patients on long-term hemodialysis with longer time-to-response than thrice weekly epoetin beta . ( Clinical Trials.gov registry No. NCT00546481 BACKGROUND C.E.R.A. , a continuous erythropoietin receptor activator , is in development to provide anemia correction and stable maintenance of hemoglobin ( Hb ) levels at extended administration intervals in patients with chronic kidney disease ( CKD ) . This study examined its efficacy and safety when administered up to once monthly in patients who have CKD and are on dialysis and r and omly convert directly from epoetin alpha or beta one to three times weekly . DESIGN , SETTING , PARTICIPANTS , AND MEASUREMENTS In this three-arm , comparator-controlled , open-label , r and omized , parallel-group , Phase III study , 572 dialysis patients ( > or = 18 yr ) who were receiving stable subcutaneous epoetin one to three times weekly were r and omly assigned ( 1:1:1 ) to continue epoetin or to receive subcutaneous C.E.R.A. once monthly or twice monthly for 52 wk . Dosage was adjusted to maintain Hb + /-1.0 g/dl of baseline level . Primary end point was mean change in Hb level between baseline and the evaluation period ( weeks 29 to 36 ) . RESULTS Mean Hb levels during the evaluation period were similar between groups ( once-monthly C.E.R.A. 11 
    Output:
    
There was insufficient evidence to compare the effect of CERA to placebo on clinical outcomes .
AUTHORS ' CONCLUSIONS There is low certainty evidence that CERA has little or no effects on patient-centred outcomes compared with placebo , epoetin alfa or beta or darbepoetin alfa for adults with CKD .