Different Dialysis Methods On Plasma Levels Of FGF-21 In Patients With End Stage Renal Disease

significance:The morbidity of end-stage renal disease(ESRD) is up to one in ten thousand, and the incidence is increasing year by year.It has become one of the major diseases which has made great impact on physical and mental health of patients, and brought a heavy financial burden to the state, society and the patients’families.The mainly treatment of ESRD at present are hemodialysis (HD), peritoneal dialysis (PD) and renal transplantation.Dialysis, as the primary treatment of patients with ESRD, is save or prolong the lives of many people. With the continuous development and updates of dialysis technology, life quality and survival rate of ESRD patients are improved.But with the extension of the duration of dialysis, many complications may occur,such as declination of residual kidney function, slightly inflammatory state, lipid metabolic disorders, renal anemia, malnutrition, chronic kidney disease mineral and bone disorder and cardiovascular events, etc.More and more medical workers get the attention of these complications. Therefore, seeking early clinical indicators as clues for dialysis related complications is necessary,and for ESRD patients,how to chose different dialysis methods and the long-term efficacy of two types of dialysis also need objective indexs to reflect.Fibroblast growth factor21, first isolated from rat embryos and determined as a new member of FGFs by Nishimura, etc in 2000, is founded to belong to FGF-19 subtribe. Its molecular sequence is composed of 210 amino acids, and it has high homology as FGF-19 and FG-F23.Anthropogenic FGF-21 genes locate on chromosome 19, mainly express in the liver, as well as skeletal muscle, white adipose tissue (WAT) and pancreas cells.FGF-21 can be detected in plasma, and relevant research supposes that it may has a function of "hormone".And as plasma levels of FGF-21 rise in metabolic diseases, it can be a molecular marker which related to early diagnosis and evaluation of disease.The activity of FGF-21 depends on its combination with FGFRs, and is closely related to β-klotho.p-klotho is necessary for FGF-21 to regulate blood sugar and lipid metabolism, as an anchor,to help FGF-21 activate FGFR mediated signal pathway and complete corresponding specific functions.And the expression of FGF-21 is regulated by different transcription factor.In the liver,it is peroxisome proliferator-activatedreceptors a(PPAR-a) that regulate FGF-21 on regulation of glucolipid metabolism.While in fat cells, it is peroxisome proliferator activatedreceptors a(PPAR-a) that regulate FGF-21.Relevant research shows that:FGF-21 can promote the absorption of glucose,improve the function of islet and reduce the accumulation of body fat.It is a new glucolipid metabolic regulation factor,which is expected to become the new therapeutic agents in the treatment of metabolic diseases such as diabetes and is likely to be an independent markers of the metabolic syndrome. For patients with cardiovascular disease,FGF-21 can adersely affect myocardial cell apoptosis and enhance antioxidant capacity, delay the onset of cardiovascular disease development in a certain extent. What is more,it has become one of international research hot spots,as it can be an early indicators of diagnosis of nonalcoholic fatty liver disease and diabetic nephropathy, and it is independently associated with low thyroid function and polycystic ovary syndrome, However, the physiological role and benefit of FGF-21 in end-stage renal disease have not been clear yet, and related research is rarely reported.The latest research indicates that:for patients with chronic kidney disease (CKD), the level of circulating FGF-21 is positively related to Scr,and negatively correlated with GFR, and from early nephropathy to end-stage renal disease, level of FGF-21 in plasma is increasing;For PD patients, RRF is negatively related to FGF-21; For AKD patients,the level of FGF-21 in plasma is also increased significantly above normal value. Studies have shown that the serum level of FGF-21 of long-term dialysis patients is 8 to 15 times as much as that of healthy subjects.The main way to eliminate FGF-21 is renal excretion, there is no clear conclusion to testify FGF-21 can be effectively removed though dialysis and the effect of different ways of dialysis (HD vs PD) on serum level of FGF-21 in ESRD patients has not been reported. A lot of ESRD patients are in chronic inflammatory state, the morbidity and mortality of cardiovascular diseases(CVD) in patients with ESRD are the first, insulin resistance is closely related to the atherosclerosis and cardiovascular mortality in patients with ESRD.Studies have found that for PD patients, interleukin-6, CRP, Fg are positively related with FGF-21, plasma FGF-21 level of PD patients with diabetes mellitus is positively related with insulin resistance index (HOMA IR); For the patients with chronic kidney disease (CKD), FGF-21 is positively correlated with Cr, BUN, ADPN, CRP, TC, and negatively correlated with GFR, HDL, LDL; Plasma FGF-21 level of patients with CVD are significantly higher than that of patients without CVD,and the state of inflammation, cardiovascular events, glucolipid metabolic disorder, malnutrition are the main risk factors that affect the survival of patients with ESRD, However, the role of plasma FGF-21 level in patients with ESRD, whether it is related to complications in the development process of disease or not is unclear.This study is to compare the differences of plasma FGF-21 levels between different dialysis patients, explore the correlation of plasma FGF-21 levels with quality of life indicators such as blood lipid, inflammation, and cardiac function in ESRD patients, analyse mechanism of high plasma FGF-21 levels in ESRD patients and explore the role of FGF-21 as a molecular marker of quality evaluation for clinical diagnosis and treatment and guiding the choice of dialysis methods in patients with ESRD.Objective:To compare the effect of different dialysis methods on indicators of life quality and the plasma levels of FGF-21 in patients with ESRD and to investigate the correlation between the FGF-21 and indicators of life quality as well as dialysis related complications.Method:211 subjects including 80 peritoneal dialysis patients (PD),47 hemodialytic patients (HD),42 ESRD patients without dialysis (ESRD) and 42 healthy control subjects were recruited.Inclusion criteria:(1) ESRD patients with regular CAPD treatment more than 3 months;(2) ESRD patients with regular hemodialysis (2-3 times/week) more than 3 months; (3) ESRD patients without dialysis (GFR< 15 ml/min); (4) medical healthy people in the same period with no history of chronic diseases,long-term drug taking; Exclusion criteria:(1) Age<18 years or>80 years; (2) unstable health condition (acute infection, heart failure, chronic viral hepatitis, malignant tumor, etc.); (3) ESRD patients with peritoneal dialysis and hemodialysis at the same time, or accepted renal transplantation; (4) acute myocardial infarction, congenital heart disease, cardiomyopathy, valvular heart disease and ejection fraction< 40%; (5)abnormal thyroid function; (6)no complete medical records.Clinical and laboratory datas were collected,including 169 cases of patients with ESRD, whose primary diseases are chronic nephritis (53.8%); diabetic nephropathy (13.0%), benign renal arteriolar sclerosis (11.2%), obstructive nephropathy (7.1%), other unknown causes (14.8%).Plasma FGF-21 and adiponectin were estimated by enzyme-linked immunosorbent (ELISA) and the clinical and biochemical parameters such as renal function(Bun, Scr), glucose and lipid metabolism (GLU, TG, TC, HDL, LDL), inflammation (CRP, Fg), nutrition state (Hb, Alb, ferroprotein), calcium phosphorus metabolism (Ca, P, iPTH) and cardiac function (LVM, LVMI, EF%) were measured. Grouping comparison, correlation analysis and multivariate regression analysis were performed.Result:(1)Comparison of different dialysis group(PD and HD) The level of BUN in HD group were higher than that of PD group (P<0.05);the level of KT/V and RRF in PD group were higher than that of HD group (P<0.05); the level of LDL in PD group was higher than that of HD group (P<0.05); the level of serum albumin in PD group was lower than that of HD group (P<0.05);the level of P and iPTH in HD group were significantly higher than PD group (P<0.05); and EF value in PD group was higher than HD group (P<0.05). Other biochemical indexes had no statistical differences.(2)Comparisons of the plasma FGF-21 levels among four groups Plasma FGF-21 levels in HD group was significantly higher than PD group as well as ESRD group (P=0.001, P=0.036); However, there was no significant difference in plasma FGF-21 level between PD group and ESRD group (P=0.388). and plasma FGF-21 levels in patients with ESRD were about eight times higher than the control group(P = 0.000).(3)Analysis on differences of the plasma levels of FGF-21 among patients with ESRD For patients with ESRD,the plasma FGF-21 levels of patients with residual renal function were significantly lower than those of patients without residual renal function(P=0.005),The plasma FGF-21 levels in patients with left ventricular hypertrophy were significantly higher than those of patients without left ventricular hypertrophy,the difference was statistically significant (P=0.001).And there were no correlations between plasma FGF-21 levels and sex,diabetes,coronary heart disease in ESRD patients (P>0.05).(4)Correlation analysis of of the plasma levels of FGF-21 among patients with ESRD Plasma FGF-21 levels in ESRD patients were inversely associated with TC,LDL,EF%(P=0.001,P=0.042,P=0.012), but correlated positively with ADPN and CRP(P=0.000,P=0.002),Multiple linear regression analysis indicated that FGF-21 was independently associated with ADPN and LDL (P=0.000,P=0.021).Conclusion:Peritoneal dialysis is better to clear urea and to protect residual renal function than hemodialysis. For patients with ESRD, different dialysis methods have different effects on indicators of protein, lipid, calcium phosphorus metabolism and cardiac function. The plasma level of FGF-21 can be used as meaningful predictors of micro-inflammatory state, lipid metabolic abnormalities, dialysis-related complications such as cardiovascular disease, which may have a certain guiding role for chosing dialysis method.