title: High-Dose Versus Conventional-Dose Continuous Venovenous Hemodiafiltration and Patient and Kidney Survival and Cytokine Removal in Sepsis-Associated Acute Kidney Injury: A Randomized Controlled Trial.
abstract: BACKGROUND
  Soluble inflammatory mediators are known to exacerbate sepsis-induced acute kidney injury (AKI). Continuous renal replacement therapy (CRRT) has been suggested to play a part in immunomodulation by cytokine removal. However, the effect of continuous venovenous hemodiafiltration (CVVHDF) dose on inflammatory cytokine removal and its influence on patient outcomes are not yet clear.
  
  
  METHODS
  Prospective, randomized, controlled, open-label trial.
  
  
  METHODS
  Septic patients with AKI receiving CVVHDF for AKI.
  
  
  METHODS
  Conventional (40mL/kg/h) and high (80mL/kg/h) doses of CVVHDF for the duration of CRRT.
  
  
  RESULTS
  Patient and kidney survival at 28 and 90 days, circulating cytokine levels.
  
  
  RESULTS
  212 patients were randomly assigned into 2 groups. Mean age was 62.1 years, and 138 (65.1%) were men. Mean intervention durations were 5.4 and 6.2 days for the conventional- and high-dose groups, respectively. There were no differences in 28-day mortality (HR, 1.02; 95% CI, 0.73-1.43; P=0.9) or 28-day kidney survival (HR, 0.96; 95% CI, 0.48-1.93; P=0.9) between groups. High-dose CVVHDF, but not the conventional dose, significantly reduced interleukin 6 (IL-6), IL-8, IL-1b, and IL-10 levels. There were no differences in the development of electrolyte disturbances between the conventional- and high-dose groups.
  
  
  CONCLUSIONS
  Small sample size. Only the predilution CVVHDF method was used and initiation criteria were not controlled.
  
  
  CONCLUSIONS
  High CVVHDF dose did not improve patient outcomes despite its significant influence on inflammatory cytokine removal. CRRT-induced immunomodulation may not be sufficient to influence clinical end points.
authors.affiliation: Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea.
authors.forename: Jung Tak
authors.initials: JT
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hajeong
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea.
authors.forename: Youn Kyung
authors.initials: YK
authors.lastname: Kee
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Seokwoo
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea.
authors.forename: Hyung Jung
authors.initials: HJ
authors.lastname: Oh
authors.affiliation: Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea.
authors.forename: Seung Hyeok
authors.initials: SH
authors.lastname: Han
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea; Kidney Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Kwon Wook
authors.initials: KW
authors.lastname: Joo
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea; Kidney Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Chun-Soo
authors.initials: CS
authors.lastname: Lim
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea; Kidney Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Yon Su
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea.
authors.forename: Shin-Wook
authors.initials: SW
authors.lastname: Kang
authors.affiliation: Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea. Electronic address: yoosy0316@yuhs.ac.
authors.forename: Tae-Hyun
authors.initials: TH
authors.lastname: Yoo
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea; Kidney Research Institute, Seoul National University, Seoul, Korea. Electronic address: dkkim73@gmail.com.
authors.forename: Dong Ki
authors.initials: DK
authors.lastname: Kim
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000209:etiology* / Q000628:therapy*; D016207:Cytokines / Q000097:blood; D005260:Female; D017583:Hemodiafiltration / Q000379:methods*; D015312:Hemodialysis Solutions / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018805:Sepsis / Q000150:complications*; D015996:Survival Rate
chemical_list: D016207:Cytokines; D015312:Hemodialysis Solutions
keywords: CRRT intensity; CVVHDF dose; Sepsis; acute kidney injury (AKI); continuous renal replacement therapy (CRRT); continuous venovenous hemodiafiltration (CVVHDF); cytokine removal; immunomodulation; inflammatory cytokines; interleukins; randomized controlled trial; sepsis-induced AKI; systemic inflammatory response syndrome