The Relationship Between Fibroblast Growth Factor 21 And Carotid Atherosclerosis In Patients With Chronic Kidney Disease

Objective:To investigate the relationship between serum fibroblast growth factor 21(FGF21)and carotid atherosclerosis in patients with chronic kidney disease(CKD)stages 3-5 in non-dialysis phase.Methods:66 patients with CKD stages 3-5 in non-dialysis phase treated in Nephrology Department of our hospital were enrolled in this study between July 2016 and July 2017.Those patients were divided into CKD stage 3(22 cases),CKD stage 4(21 cases)and CKD stage 5(23 cases)according to estimated glomerular filtration rate(eGFR).In addition,20 healthy subjects who were matched for age and sex were selected as healthy control group and the clinical data of all patients and healthy controls were collected,including age,sex,weight,height,body mass index(BMI),systolic blood pressure(SBP),diastolic blood pressure(DBP),primary kidney disease,diabetes mellitus and laboratory indicators such as fasting blood glucose(FBG),triglyceride(TG),totalcholesterol(TC),high density lipoprotein cholesterol(HDL-c),low density lipoprotein cholesterol(LDL-c),albumin(Alb),blood urea nitrogen(BUN),serum creatinine(Scr).eGFR was calculated by using the modified original simplified Modification of Diet in Renal Disease(MDRD).C-reactive protein(CRP)was measured by rate nephelometry.The level of serum FGF21 was measured by enzyme-linked immunosorbent assay(ELISA).The difference of serum FGF21 level between patients with CKD stages 3-5 in non-dialysis phase and healthy control group as well as the difference of serum FGF21 level between CKD stage 3,CKD stage 4 and CKD stage 5 were compared,and their clinical significance was analyzed.The carotid intima-media thickness(IMT)and atherosclerotic plaques were measured by color Doppler ultrasound.According to the results,patients with CKD stages 3-5 in non-dialysis phase were classified into carotid atherosclerosis group(CAS group)and non-carotid atherosclerosis group(non-CAS group),and comparing the changes of the parameters between the two groups.The correlation between serum FGF21 and carotid atherosclerosis and its clinical significance were explored.Results:1.The incidence of carotid atherosclerosis in patients with CKD stages 3-5 in non-dialysis phase was 53.0%(35/66).The level of serum FGF21 and age in CAS group were significantly higher than those in non-CAS group(P<0.05).2.The level of serum FGF21 and CRP in patients with CKD stages 3-5 in non-dialysis phase were significantly higher than those in healthy controls(P<0.05);and Alb in patients with CKD stages 3-5 in non-dialysis phase was significantly lower than that in healthy controls(P<0.05).3.The level of serum FGF21 in CKD stage 3,CKD stage 4 and CKD stage 5 [(355.3 ± 96.8),(602.7 ± 94.3),(1136.7 ± 251.4)ng / L] increased progressively with deteriorating renal function.The level of serum FGF21 in CKD stage 3 as well as CKD stage 4 and CKD stage 5 was significantly higher than that in healthy controls(P<0.01).FBG in CKD stage 3 was significantly higher than that in CKD stage 4 and CKD stage 5(P<0.05).TG in CKD stage 5 was significantly higher than that in CKD stage 3(P<0.05).4.Pearson correlation analysis showed that the level of serum FGF21 was positively correlated with TG(r= 0.283,P=0.021),Scr(r= 0.761,P<0.001),IMT(r= 0.532,P<0.001),while negatively correlated with TC(r=-0.383,P=0.001),LDL-c(r=-0.253,P=0.040),eGFR(r=-0.818,P<0.001).No correlation was found between FGF21 and HDL-c(r= 0.130,P=0.297).Conclusions:The incidence of carotid atherosclerosis in patients with CKD stages 3-5 in non-dialysis phase is relatively high,and the level of serum FGF21 in patients with CKD in non-dialysis phase is correlated with carotid atherosclerosis.With the development of CKD,the level of serum FGF21 increased progressively and was significantly higher than that in healthy controls.It is speculated that renal excretion may be the main pathway of FGF21 clearance.Serum FGF21 may be a new biomarker to detect the decline of renal function.FGF21 may play an important role in the development of carotid atherosclerosis in patients with CKD.Serum FGF21 may become one of the sensitive markers to predict atherosclerosis.