title: Extracellular Fluid/Intracellular Fluid Volume Ratio as a Novel Risk Indicator for All-Cause Mortality and Cardiovascular Disease in Hemodialysis Patients.
abstract: BACKGROUND
  In hemodialysis patients, fluid overload and malnutrition are accompanied by extracellular fluid (ECF) expansion and intracellular fluid (ICF) depletion, respectively. We investigated the relationship between ECF/ICF ratio (as an integrated marker reflecting both fluid overload and malnutrition) and survival and cardiovascular disease (CVD) in the context of malnutrition-inflammation-arteriosclerosis (MIA) complex.
  
  
  METHODS
  Seventy-seven patients from a single hemodialysis unit were prospectively enrolled. The ECF/ICF volume was measured by segmental multi-frequency bioimpedance analysis. MIA and volume status were measured by serum albumin, C-reactive protein (CRP), pulse wave velocity (PWV) and plasma B-type natriuretic peptide (BNP), respectively.
  
  
  RESULTS
  The mean ECF/ICF ratio was 0.56±0.06 and the cut-off value for maximum discrimination of survival was 0.57. Compared with the low ECF/ICF group, the high ECF/ICF group (ratio≥0.57, 42%) had higher all-cause mortality, CVD, CRP, PWV, and BNP, but lower serum albumin. During the 5-year follow-up, 24 all-cause mortality and 38 CVD occurred (18 and 24, respectively, in the high ECF/ICF group versus 6 and 14 respectively in the low ECF/ICF group, P<0.001). In the adjusted Cox analysis, the ECF/ICF ratio nullifies the effects of the MIA and volume status on survival and CVD and was an independent predictor of all-cause mortality and CVD: hazard ratio (95% confidence interval); 1.12 (1.01-1.25) and 1.09 (1.01-1.18) for a 0.01 increase in the ECF/ICF ratio. The degree of malnutrition (albumin), inflammation (CRP), arteriosclerosis (PWV), and fluid overload (BNP) were correlated well with the ECF/ICF ratio.
  
  
  CONCLUSIONS
  Hemodialysis patients with high ECF/ICF ratio are not only fluid overloaded, but malnourished and have stiff artery with more inflammation. The ECF/ICF ratio is highly related to the MIA complex, and is a major risk indicator for all-cause mortality and CVD.
authors.affiliation: Department of Internal Medicine, Hallym Kidney Research Institute, College of Medicine, Hallym University, Chuncheon, Korea.|Division of Nephrology, Dongtan Sacred Heart Hospital, Hallym University Medical Center, Hwaseong-si, Korea.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Hallym Kidney Research Institute, College of Medicine, Hallym University, Chuncheon, Korea.
authors.forename: Myung-Jin
authors.initials: MJ
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, Hallym Kidney Research Institute, College of Medicine, Hallym University, Chuncheon, Korea.
authors.forename: Jeoung-Hwan
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Hallym Kidney Research Institute, College of Medicine, Hallym University, Chuncheon, Korea.
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Oh
authors.affiliation: Department of Internal Medicine, Hallym Kidney Research Institute, College of Medicine, Hallym University, Chuncheon, Korea.|Division of Nephrology, Dongtan Sacred Heart Hospital, Hallym University Medical Center, Hwaseong-si, Korea.
authors.forename: Jang-Won
authors.initials: JW
authors.lastname: Seo
authors.affiliation: Department of Internal Medicine, Hallym Kidney Research Institute, College of Medicine, Hallym University, Chuncheon, Korea.
authors.forename: Young-Ki
authors.initials: YK
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Hallym Kidney Research Institute, College of Medicine, Hallym University, Chuncheon, Korea.
authors.forename: Jong-Woo
authors.initials: JW
authors.lastname: Yoon
authors.affiliation: Department of Internal Medicine, Hallym Kidney Research Institute, College of Medicine, Hallym University, Chuncheon, Korea.
authors.forename: Hyung-Jik
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Hallym Kidney Research Institute, College of Medicine, Hallym University, Chuncheon, Korea.
authors.forename: Jung-Woo
authors.initials: JW
authors.lastname: Noh
authors.affiliation: Department of Internal Medicine, Hallym Kidney Research Institute, College of Medicine, Hallym University, Chuncheon, Korea.|Division of Nephrology, Dongtan Sacred Heart Hospital, Hallym University Medical Center, Hwaseong-si, Korea.
authors.forename: Ja-Ryong
authors.identifier: http://orcid.org/0000-0003-4245-2569
authors.initials: JR
authors.lastname: Koo
mesh_terms: D001161:Arteriosclerosis / Q000473:pathology*; D002097:C-Reactive Protein / Q000032:analysis; D045604:Extracellular Fluid / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D007424:Intracellular Fluid / Q000378:metabolism*; D008137:Longitudinal Studies; D008297:Male; D044342:Malnutrition / Q000473:pathology*; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D011446:Prospective Studies; D063177:Pulse Wave Analysis; D006435:Renal Dialysis / Q000401:mortality*; D012307:Risk Factors; D012709:Serum Albumin / Q000032:analysis
chemical_list: D012709:Serum Albumin; D020097:Natriuretic Peptide, Brain; D002097:C-Reactive Protein