Researches On Vascular Calcification And Outcomes In Maintenance Hemodialysis Patients

Objectives:The cardiovascular complications hitherto remain as the leading cause of MHD patients mortality.Vascular calcification,an important part of the chronic mineral-bone disorder,has played an vital role in increasing the high prevalence of cardiovascular diseases and mortality in MHD.It is of great importantance to evaluate vascular calcification in time so as to decrease the CVD mortality and increase the survival rate of MHD patiens.Fibroblast growth factor-23 is a key regulator of calcium-phosphorus metabolism.Currently,the relationships among FGF23,vascular calcification and mortality are still uncertain.Inflammation is one of the independent risk factors of the CVD comordities and mortality of MHD patients.Clinical studies revealed that hemodiafiltration(HDF)could alleviate the dialysis patients` inflammation states as a result of increasing the survival rates.The aim of this study were as follows:1)to evaluate the assoiation between FGF23 and vascular calcification;2)to learn the relationship among vascular calcification,inflammation,FGF23 and mortality in MHD patients;3)to explore the underlying mechanism of oL-HDF on the function of alleviating inflammation and decreasing the prevalence of CVD.Methods: 1)One hundred and fourteen cases MHD patients were selceted by the crteria of dialysis duration exceed three months in the Shanghai Jiaotong medical university affiliated of Renjihospital.2)Abdomen lateral plian was used as a criteria to determine abdominal aortic calcifiction and the abdominal aortic calcification score(AACS)was counted.According to the CORD study,dividing into two group:non or light abdominal aortic calcification(AACS<5),moderate to severe abdominal aortic calcification(AACS ≥ 5).The prevelance of abdominal aortic calcification and the association with mortality in MHD patients were analysied.3)The sreum level of intach FGF23 was tested by ELISA.According to the quartile of the level of FGF23,to explore the association of serum FGF23 with abdominal aortic calcification and mortality in MHD patients.4)Forty cases MHD patients were selceted by the crteria of dialysis duration exceed three months in the Shanghai Jiaotong medical university affiliated of Renji hospital,among which oL-HDF group was twenty-two,conventional HD group was eighteen.The Th17 cells and Treg cells were counted by flow cytometry.The key transcription factors of Th17 and Treg are tested by RT-qPCR.ELISA was used to test the inflammation factors.Results: 1)There were seventy-six cases exist abdominal aortic calcification,sixty-one cases of non or light calcification,fifity-three of moderate to severe calcification.The age,dialysis vintage and smoking history were the independent risk factors of AAC.The median follow-up duration was 72.0(67.8,72.8)months.During the follow-up,22 patients(19.3%)died of all-cause death and 17 cases(14.9%)died of cardiovascular diseases.Kaplan-Meier survial curves showed that the patients with AACS ≥ 5 had significantly higher all-cause mortality(P=0.028)and CVD mortality(P=0.035)than those with AACS<5.Multivariable COX regression demonstrated that AACS was the independent risk factor of CVD mortality in MHD patients.hsCRP was the independent risk factor both of all-cause mortality and CVD mortality in MHD patients.2)Spearmen analysis showed that FGF23 was positive correlated with dialysis vintage,BMI,AACS,Scr,Ca,P,CaxP and iPTH and negative correlated with age(P<0.05).Logistic regression analysis showed that higher FGF23level(OR=2.831,95% CI 1.010~7.937,P=0.048)were the independent risk factors of moderate to severe AAC in MHD patients.Kaplan-Meier analysis showed no significant differences of the level of serum FGF23 with the all-cause and CVD mortality.COX regression analysis demonstrated that FGF23 was not associated with increased mortality risk.In the subgroup of AACS<5 or AACS≥5 was still not associated with increased mortality risk neither in crude nor in multivariate adjusted models.3)Compared to the conventional HD group,the group of oL-HDF patients had longer dialysis vintage,higher Kt/v and lower prealbumin,ferritin and hsCRP.But the difference of hsCRP was not significant(1.28mg/L vs2.56mg/L,P=0.131).The percentage of Th17 cells in oL-HDF group was lower than in the HD group(1.51 vs 1.74,P=0.430),and the percentage of Treg cells was higher(3.14 vs 2.75,P=0.368),the ratio of Th17/Treg was lower(0.44 vs 0.66,P=0.232).The key transcription factors of Th17 were lower in oL-HDF group and those of Treg were higher when compeared to the conventonal HD group(RORγt 1.74 vs 2.12,P=0.608,Foxp3 0.86 vs0.67,P=0.154).Similarly,the level of plasma IL-6 was lower in oL-HDF and the level of plasma IL-10 was higher than in conventional HD group(IL-61.66pg/ml vs 2.00pg/ml,P=0.216;IL-10 3.94pg/ml vs 3.75pg/ml,P=0.429).Conclusions:1.Abdominal aortic calcification had a high prevalence in MHD patients.The all-cause and CVD mortality was higher in patients with moderate to severe AAC.AACS was the independent risk factor of CVD mortality.2.hsCRP was associated independently both with all-cause mortality and CVD mortality among MHD.3.FGF23 was the the independent risk factor of moderate to severe AAC,but it may not be a predictor for theall-cause and CVD mortality of MHD patients.4.oL-HDF may regulate the ratio imbalance of Th17/Treg so as to alleviate the inflammation state and decreasing the prevalence of CVD in MHD patients,but multi-center and large sample studies are still necessary to confirm it.