***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: Objective Patients with cardiorenal syndrome ( CRS ) have high cardiovascular morbidity . Endothelial progenitor cells ( EPC ) constitute an endogenous vascular repairsystem , protecting against atherosclerosis development . Erythropoietin ( EPO ) treatment may have beneficial effects by mobilizing EPC from the bonemarrow . Our objective is to determine EPC levels and effects of EPO therapy on EPC levels in CRS patients . Design Open-label r and omized trial . Setting Part of the EPOCARES-trial , conducted in Utrecht ( Netherl and s ) . Patients Patients with CRS and anaemia and healthy controls were included . Interventions Patients were r and omized to receive EPO therapy ( 50 IU/kg/wk ) for 52 weeks or no EPO therapy . Main outcome measures CD34+KDR+-EPC , cultured EPC outgrowth and function at baseline , after 18 days and after 52 weeks . Results Patients showed lower CD34+KDR+-cell numbers compared to controls ( 6(12 ) vs. 19(19 ) cells/105 granulocytes ; p=0.010 ) , despite increased levels of stromal cell-derived factor-1α ; ( 3.1(0.8 ) vs 2.6(0.3 ) ng/ml ; p=0.001 ) . EPC outgrowth and function were not different between patients and controls . EPC levels did not change after 18 days with or without EPO treatment . CD34+KDR+-cells significantly declined after 52 weeks in the non-treated group ( p=0.028 ) . Long-term EPO therapy did not significantly affect this reduction in CD34+KDR+-EPC levels . Conclusions CRS patients showed reduced CD34+KDR+-EPC levels compared to controls , consistent with a reduced vascular regenerative potential and despite upregulated SDF-1α levels . Over a one-year follow-up period a marked 68 % further reduction in EPC levels was observed in the patient group without EPO treatment . In spite of promising experimental studies , our longitudinal , r and omized study did not show significant influence of either short- or long-term EPO therapy on reduced EPC levels in CRS patients OBJECTIVE The use of erythropoietin ( EPO ) for the amelioration of anemia has dramatically changed the quality of life of the patients with chronic renal failure ( CRF ) . The efficacy of a low dose EPO therapy was assessed in the prospect i ve 6 week trial . METHODS Assessment of hematological parameters and iron stores was done in 40 patients of CRF : Group A--20 patients of CRF receiving 40 U/kg EPO biweekly for 6 weeks and Group B--20 patients of CRF not receiving EPO .  The parameters were studied at the start and at 2 , 4 and 6 weeks of the study . RESULTS A statistically significant rise in mean haemoglobin levels ( 7.27 + /- 1.26 g/dl to 8.60 + /- 1.66 g/dl ) ; mean packed cell volume ( 21.4 + /- 4.04 % to 25.4 + /- 6.54 % ) and mean reticulocyte count ( 1.28 + /- 0.4 % to 2.14 + /- 0.86 % ) was observed on EPO therapy . Patients on EPO developed a significant decline in serum iron , serum ferritin levels , bone marrow iron stores ; and a hypochromic-microcytic picture on the peripheral blood film suggestive of iron deficiency . Iron deficiency at the start , chronic infections like tuberculosis and inadequate haemodialysis were identified as causes of hyporesponsiveness to EPO therapy . Low dose EPO therapy was not associated with any major adverse effects . CONCLUSIONS Low dose EPO ( 40 U/kg , biweekly ) therapy is safe and effective in the management of anaemia of CRF Background Combined heart and renal failure is associated with high cardiovascular morbidity and mortality . Anti-oxidant and anti-inflammatory , non-hematopoietic effects of erythropoietin ( EPO ) treatment have been proposed . Monocytes may act as biosensors of the systemic environment . We hypothesized that monocyte transcriptomes of patients with cardiorenal syndrome ( CRS ) reflect the pathophysiology of the CRS and respond to short-term EPO treatment at a recommended dose for treatment of renal anemia . Methods Patients with CRS and anemia ( n = 18 ) included in the EPOCARES trial were matched to healthy controls ( n = 12 ) . Patients were r and omized to receive 50 IU/kg/week EPO or not . RNA from CD14 + -monocytes was subjected to genome wide expression analysis ( Illumina ) at baseline and 18 days ( 3 EPO injections ) after enrolment . Transcriptomes from patients were compared to healthy controls and effect of EPO treatment was evaluated within patients . Results In CRS patients , expression of 471 genes , including inflammation and oxidative stress related genes was different from healthy controls . Cluster analysis did not separate patients from healthy controls . The 6 patients with the highest hsCRP levels had more differentially expressed genes than the 6 patients with the lowest hsCRP levels . Analysis of the variation in log2 ratios of all individual 18 patients indicated that 4 of the 18 patients were different from the controls , whereas the other 14 were quite similar . After short-term EPO treatment , every patient clustered to his or her own baseline transcriptome . Two week EPO administration only marginally affected expression profiles on average , however , individual gene responses were variable . Conclusions In stable , treated CRS patients with mild anemia , monocyte transcriptomes were modestly altered , and indicated imprints of inflammation and oxidative stress . EPO treatment with a fixed dose has hematopoietic effects , had no appreciable beneficial actions on monocyte transcription profiles , however , could also not be associated with undesirable transcriptional responses Results from animal experiments have suggested that treatment with recombinant human erythropoietin ( rHuEPO ) causes changes in renal hemodynamics which are detrimental to renal function . Therefore , the effects of correction of the anemia by rHuEPO on glomerular filtration rate ( GFR ; inulin clearance ) and effective renal plasma flow ( ERPF ; PAH clearance ) were studied in eight pre-dialysis patients . The studies were done before ( Hct 0.24 + /- 0.05 liter/liter ) and at 89 + /- 19 days after the start of rHuEPO therapy ( Hct 0.39 + /- 0.03 liter/liter ) . To further evaluate the effects of ACE inhibition , 25 mg of captopril was given orally after baseline values had been obtained . Baseline GFR , renal blood flow ( RBF ) and filtration fraction ( FF ) did not change during rHuEPO therapy . At low hematocrit ( Hct ) captopril induced a significant increase in ERPF and RBF , and a decrease in MAP . After correction of the hematocrit the blood pressure lowering effect of captopril remained unchanged . However , captopril no longer induced changes in ERPF and RBF . We conclude that the increase in hematocrit had no adverse effects on GFR . The results suggest that changes in hematocrit may influence the effects of ACE inhibition on efferent vascular resistance . Therefore , the hematocrit should be taken into account when evaluating studies on the effects of ACE inhibition in the progression of chronic renal failure Partial correction of anemia in patients with chronic kidney disease ( CKD ) reduces left ventricular hypertrophy ( LVH ) , which is a risk factor for cardiovascular ( CV ) morbidity , but complete correction of anemia does not improve CV outcomes . Whether LV geometry associates with CV events in patients who are treated to different hemoglobin ( Hb ) targets is unknown . One of the larger trials to study the effects of complete correction of anemia in stages 3 to 4 CKD was the Cardiovascular Risk Reduction by Early Anemia Treatment with Epoetin Beta ( CREATE ) trial . Here , we analyzed echocardiographic data from CREATE to determine the prevalence , dynamics , and prognostic implication s of abnormal LV geometry in patients who were treated to different Hb targets . The prevalence of LVH at baseline was 47 % , with eccentric LVH more frequent than concentric . During the study , LVH prevalence and mean left ventricular mass index did not change significantly , but LV geometry fluctuated considerably within 2 yr in both groups . CV event-free survival was significantly worse in the presence of concentric LVH and eccentric LVH compared with the absence of LVH ( P = 0.0009 and P < or = 0.0001 , respectively ) . Treatment to the higher Hb target associated with reduced event-free survival in the subgroup with eccentric LVH at baseline ( P = 0.034 ) . In conclusion , LVH is common and associates with poor outcomes among patients with stages 3 to 4 CKD , although both progression and regression of abnormal LV geometry occur . Complete anemia correction may aggravate the adverse prognosis of eccentric LVH BACKGROUND Polymorphonuclear leukocyte priming and low grade inflammation are related to severity of kidney disease . Erythropoietin-receptor is present on PMNLs . OBJECTIVES xi : To evaluate the effect of 20 weeks of epoetin-alpha treatment on PMNL characteristics in relation to the rate of kidney function deterioration in patients with chronic kidney disease . METHODS Forty anemic chronic kidney disease patients , stage 4 - 5 , were assigned to EPO and non-EPO treatment for 20 weeks . A group of 20 healthy controls was also studied . PMNL priming and PMNL-derived low grade inflammation were estimated , in vivo and ex vivo , before and after EPO treatment : The rate of superoxide release , white blood cells and PMNL counts , serum alkaline phosphatase and PMNL viability were measured . EPO-receptor on PMNLs was assayed by flow cytometry . The effect of 20 weeks of EPO treatment on kidney function was related to the estimated glomerular filtration rate . esults : EPO treatment attenuated superoxide release ex vivo and in vivo and promoted PMNL survival ex vivo . Decreased low grade inflammation was reflected by reduced WBC and PMNL counts and ALP activity following treatment . EPO retarded the deterioration in GFR . The percent of PMNLs expressing EPO-R was higher before EPO treatment and correlated positively with the rate of superoxide release . After 20 weeks of EPO treatment the percent of PMNLs expressing EPO-R was down-regulated . CONCLUSIONS These non-erythropoietic properties of EPO are mediated by EPO-R on PMNLs , not related to the anemia correction . A new renal protection effect of EPO via attenuation of PMNL priming that decreases systemic low grade inflammation and oxidative stress is suggested A study was undertaken to ascertain the effects of recombinant human erythropoietin ( r-HuEPO ) on renal function in chronic renal failure predialysis patients . The effect of improvement of anemia by r-HuEPO on the rate of decline in renal function in predialysis patients has not been previously studied prospect ively in a large number of patients using reliable measures of glomerular filtration rate ( GFR ) . To investigate the efficacy , safety , and impact of r-HuEPO therapy in chronic renal insufficiency patients , a 48-week , r and omized , open-label , multicenter study was initiated in 83 anemic , predialysis ( serum creatinine 3 to 8 mg/dL ) patients . Serial GFRs were measured using 125I-iothalamate clearance . Forty patients were r and omized to the untreated arm and 43 patients to the treatment arm ( 50 U/kg r-HuEPO  subcutaneously three times weekly ) . Baseline characteristics were comparable for the r-HuEPO-treated and untreated groups . During this 48-week study , GFR , mean arterial blood pressure , and daily protein intake were not significantly different between the two groups . There was a statistically significant increase in hematocrit for the r-HuEPO-treated group that was not associated with acceleration of deterioration in residual renal function . This was demonstrated by the lack of a significant ( P = 0.376 ) between-group difference in mean change in GFR from baseline to last available value for the r-HuEPO-treated ( -2.1 + /- 3.2 mL/min ) and untreated ( -2.8 + /- 3.5 mL/min ) groups . This study concludes that r-HuEPO therapy improves  anemia in predialysis patients and does not accelerate the rate of progression to end-stage renal disease The investigators evaluated the impact of recombinant human erythropoietin ( r-HuEPO ) therapy on health-related quality of life ( HRQL ) in predialysis chronic renal disease patients with anemia . Eighty-three patients were entered into a r and omized , parallel-group , open-label clinical trial with follow-up evaluations over 48 weeks . Forty-three patients were assigned to r-HuEPO treatment , and 40 patients were assigned to an untreated control group .  Hematocrit levels were measured at baseline and monthly . HRQL was assessed at baseline and at weeks 16 , 32 , and 48 . The HRQL assessment included measures of physical function , energy , role function , health distress , cognitive function , 
    Output:
    
The data from studies reporting quality of life or exercise capacity demonstrated an improvement in the treatment group .
Most of the measures of progression of kidney disease showed no statistically significant difference .
No significant increase in adverse events was identified .
Treatment with rHuEPO in predialysis patients corrects anaemia , avoids the requirement for blood transfusions and also improves quality of life and exercise capacity .
We were unable to assess the effects of rHuEPO on progression of kidney disease , delay in the onset of dialysis or adverse events .