Application Of Hemoglobin Variability And Hepcidin In Renal Anemia Of Maintenance Hemodialysis Patients

Objective: To analysis hemoglobin(Hb)compliance rate and anemia parameters of maintenance hemodialysis(MHD)patients in Shanghai Ruijin Hospital from Jan.2011 to Jul.2015,to explore the effect of increasing Hb detecting frequency on Hb variability,to investigate the potential factors associated with high Hb varibility and the association of Hb varibility with adverse outcome,and to identify the influential factors of plasma hepcidin level.Methods:(1)MHD patients in Shanghai Ruijin Hospital from Jan.2011 to Jul.2015 were included in this study.Hb compliance rate,anemia parameters,erythropoiesis stimulating agent(ESA)and intravenous(IV)iron use were regularly assessed semiannually.(2)MHD patients were enrolled in Jan.2011.Hb levels were detected once every 2 moths from Jan.2011 to Dec.2012 and monthly from Jan.2013 to Dec.2014.Hb variability was described by different measurements.(3)A single-center,prospective and cohort study enrolled MHD patients from Jan.1st,2011 to Dec.31 th,2011.Clinical characteristics and biochemical indexs were collected at baseline.Hb levels were regularly measured every 2 months during the 1-year observation period and then followed up all patients to Dec.2015.All-cause and cardiovascular disease(CVD)death were collected.(4)Bood samples at baseline were collected to detect plasma hepcidin level using ELISA method.Analyse the relationship among hepcidin,Hb varibility indexes,anamia parameters,LVH and abdominal aortic calcification(AAC).Results:(1)A total of 2613 MHD patients were included.Red blood cell(RBC)and weekly ESA dose in Jul.2015 increased significantly than Jan.2011(P=0.012,<0.001,respectively),ferritin and transferrin saturation(TSAT)decreased significantly than Jan.2011(both P <0.001).Hb target level was defined as Hb level ?110g /L.Hb compliance rate were 46.78%,47.46%,47.33%,47.06%,44.60%,48.16%,47.19%,47.64%,50.18% and 51.07% in different time points.Hb compliance rate of male patients was significantly higher than female in 45-64 year-old(P=0.012).Hb compliance rate of male patients was slightly higher than female in 65-74 year-old and over 75 year-old(P=0.486,0.694,respectively).However,Hb compliance rate of male patients is slightly lower than female in 20-44 year-old(P=0.458).IV iron use rate were 11.59%,10.55%,10.69%,12.94%,21.22%,10.99%,13.11%,11.37%,12.82% and 13.21% in different time points.(2)133 MHD patients were enrolled in this study.Hb residual standard deviation(SD),intraindividual change in Hb and SD of intraindividual change in Hb of detecting once every 2 months were notably higher than that of monthly detecting.Two groups patients mainly exhibited high-amplitude fluctuation(HA),with detecting once every 2 months accounting for 72.18% and monthly 74.44%.Low-amplitude fluctuation with low Hb levels(LAL)accounted for 20.30% and 18.80%,and low-amplitude fluctuation with high Hb levels(LAH)were 2.26% and 3.76%,consistently low(CL)4.51% and 1.50%,consistently high(CH)0.75% and 1.50%,respectively.No patients were in consistently within the target range(CT)in two groups.There was no significant difference between the two groups based on fluctuations across thresholds.Distribution based on Hb amplitude mainly in >20g /L category,with detecting once every 2 months accounting for 63.16% and monthly 69.17%.The proportion of MHD patients in 11~20g /L category were 30.83% and 30.83%,respectively.The proportion in 0~10g /L category were 6.02% and 0.00%,respectively.Significant difference was found in two groups according to Hb amplitude.(3)A total of 255 MHD patients were involved in this study.In Logistic regression analysis,lower body mass index(BMI),lower transferrin level,change of vascular access type and higher erythropoitin resistance index(ERI)were independently associated with higher variability of Hb level.After 3-year follow-up,26.67%(68 of 255)of MHD patients died.Kaplan-Meier analysis showed MHD patients in LAH category had the significantly greatest risk for all-cause and CVD mortality(P=0.039,0.015).Risk of all-cause death in LAH category was 1.89 times(95 % CI,0.81-4.40)than in LAL category,while risk of CVD mortality was 4.38 times(95 % CI,1.58-12.15).From the result of multivariate analyses,older age,higher pre-HD systolic pressure(SBP),history of diabetes,higher red blood cell distribution width(RDW),lower albumin,lower urea reduction rate(URR)and lower blood flow rate were apparently significant risk factors associated with all-cause mortality.Older age,higher pre-HD SBP,higher RDW,lower mean corpuscular hemoglobin(MCH)and lower URR were apparently significant factors related to CVD mortality.(4)216 MHD patients were enrolled in final analysis.Plasma hepcidin level was 2952.66(1131.38-6076.72)pg /ml.In Spearman analysis,significant negative correlations were observed between hepcidin and RBC,Hb,HCT,total iron binding capacity(TIBC)and transferrin,while significant positive correlations were between hepcidin and MCH,mean corpuscular hemoglobin concentration(MCHC),TSAT,ferritin,C-reactive protein(CRP)and weekly ESA dose.Stepwise multiple-regression analysis showed that the independent parameters associated with hepcidin were BMI,ferritin,TIBC and CRP.Hepcidin level was positively correlated with AAC.There were no significant association of hepcidin with Hb variability and echocardiography indexes.Conclusion: Although Hb compliance rate in our center increased gradually,the overall compliance rate is still low,and weekly ESA dose rised.Evaluation of iron metabolism became more and more important in MHD patients.Although IV iron use rate of MHD patients in our center was not very high,mean serum iron,ferritin and TSAT level still reached the target.Increasing the frequency of hemoglobin detection could obviously reduce hemoglobin variability and keep Hb level stable.Hb variability wasn't independently associated with increased risks of mortality.However,MHD patients in LAH category might have the highest all-cause and CVD mortality,but this finding needs to be interpreted cautiously.Hepcidin level was related to anemia parameters and iron metabolism indicators,and was also associated with inflammation factors and AAC.