Sarcopenia In Maintenance Hemodialysis Patients Of Zhengzhou: Prevalence, Risk Factors And Prognosis

Background and ObjectiveSarcopenia,a muscle wasting syndrome mainly characterized by the atrophy of skeletal muscle,along with the decreases of muscle strength and function with age,is prevalent and particularly prominent among maintenance hemodialysis patients(MHD).According to previous studies,the incidence of sarcopenia in MHD patients ranged from 3.9% to 63.3%.It is associated with increase risk of adverse outcomes such as poor quality of life,the risk of falls and fractures,the rate of hospitalization and mortality for those patients who suffer from hemodialysis.Irisin,a novel polypeptide hormone,is formed after fibronectin type III domain containing 5(FNDC5)proteolytically cleaved.Following skeletal muscle injury,irisin can induce its regeneration and hypertrophy,which implies that irisin may have potential therapeutic benefit in overcoming skeletal muscle wasting.This study aim at evaluating the prevalence,risk factors and long-term outcomes of sarcopenia in MHD patients.Furthermore,with the purpose of analyzing irisin's impact on prognosis and effects on myoblasts autophagy.This study can provide scientific evidences for clinical prevention and treatment.Materials and methodsAccording to inclusion/exclusion criteria,180 MHD patients were enrolled in our study from four blood purfication centres in Zhengzhou.Through collecting questionnaires kept record of demographic and clinical data(include gender,age,medical insurance,dialysis duration,primary cause of the kidney,and comorbidities),they completed modified quantitative subjective global assessment(MQSGA)questionnaire at the same time.Blood was taken in the midweek both before and after hemodialysis,and the following laboratory date were measured in hospital laboratories.Body compositions were tested with bioelectrical impedance analysis(BIA)before starting hemodialysis.Serum irisin concentrations were measured by ELISA.Autophagy related proteins expression were detected by Western Blot in murine C2C12 myoblasts.Sarcopenia were defined by skeletal muscle mass index(SMI),handgrip strength(HGS)and gait speed(GS)by AWGS.Based on the diagnostic results,all patients were divided into sarcopenia group and non-sarcopenia group and followed up for three year.This study aimed to analyze the incidence,risk factors and prognosis of sarcopenia in MHD patients.Furthermore,with the purpose of analyzing irisin's impact on prognosis and effect on myoblasts autophagy.Results1.One hundred and eighty MHD patients were enrolled in this study,in which 57.2% of patients were male.The mean age was 49.90 ±12.74 years and the median dialysis duration was 36 months.The incidence of sarcopenia within the MHD patients was 25%.2.Compared demographic data and laboratory examinations between sarcopenia group and non-sarcopenia group patients,significant differences between the two groups in the aspects of age,with or without diabetes,MQSGA scores(P < 0.05).Sarcopenia group were characterized by some clinical properties: lower serum levels of ALB,BUN,Crea,kt/V,nPCR,irisin and higher levels of C-reaction protein(CRP)(P < 0.05).While there was no significantly differences in the aspects of gender,dialysis duration(m),SBP,DBP,HGB,Ca,P,TCHO,TG,iPTH,ferritin(P > 0.05).3.Compared anthropometric measurement between sarcopenia group and non-sarcopenia group patients: LBM,MAC,MAMC were significantly decreased in non-sarcopenia group(P < 0.05),while FM were significantly increased than which in non-sarcopenia group(P < 0.05).However,the comparisons of BMI?TSF?WHR between two groups showed no significantly statistical difference(P > 0.05).4.Multivariate analysis showed that,age ? 60 yrs(OR = 3.91,95% CI =2.18~7.02,P < 0.001,MQSGA scores >10(OR = 3.76,95% CI= 2.17~6.52,P < 0.001),lower Irisin levels [Ref VS(OR = 3.72,95% CI = 1.64~8.41)VS(OR = 6.41,95% CI = 2.81~14.61)VS(OR = 13.42,95% CI = 5.02~35.85),P < 0.001] were independent risk factors for sarcopenia in MHD patients.MAMC was protective factor(OR = 0.73,95% CI= 0.65~0.83,P<0.001).5.Multivariate linear regression analysis was performed to identify variables strongly associated with irisin in HD patients: SMI(B = 5.24,95% CI = 1.92~8.55,P = 0.002),Scr(B = 0.02,95% CI = 0.01~0.04,P = 0.01),Kt/V(B = 4.62,95% CI = 3.00~6.28,P < 0.001)were independently associated with irisin.6.Kaplan–Meier survival analysis showed a 77.4% three-year survival rate in the sarcopenia group,which was significantly lower than that in the non-sarcopenia group(P < 0.001),and an 84.1% three-year survival rate in lower serum irisin level,which was significantly lower than that in the higher serum irisin group(P = 0.01).7.Western Blot analysis autophagy related genes expressionCompared with control group,the expressions of Atg-3,Atg-12 and Beclin-1 in indoxyl sulfate(IS)group were significantly increased(P < 0.05),whereas irisin treatment(250ng/ml)resulted in the down-regulation of the expression of Atg-3(P < 0.05),and irisin treatment(1000ng/ml)resulted in the down-regulation of the expressions of Atg-3,Atg-12 and Beclin-1 compared with IS group.Conclusions1.The high incidience of sarcopenia in MHD patients.2.Age,malnutrition,lower serum irisin level were the risk factor for sarcopenia in MHD patients.3.The mortality of sarcopenic patients was higher than that of non-sarcopenic patients.4.Irisin can ameliorated myoblasts autopahgy induced by IS.