title: Earlier versus later initiation of renal replacement therapy among critically ill patients with acute kidney injury: a systematic review and meta-analysis of randomized controlled trials.
abstract: BACKGROUND
  Although the optimal timing of initiation of renal replacement therapy (RRT) in critically ill patients with acute kidney injury has been extensively studied in the past, it is still unclear.
  
  
  METHODS
  In this systematic review, we searched all related randomized controlled trials (RCTs) that directly compared earlier and later RRT published prior to June 25, 2016, from PubMed, MEDLINE, and EMBASE. We extracted the study characteristics and outcomes of all-cause mortality, RRT dependence, and intensive care unit (ICU) and hospital length of stay (LOS).
  
  
  RESULTS
  We identified 51 published relevant studies from 13,468 screened abstracts. Nine RCTs with 1627 participants were included in this meta-analysis. Earlier RRT was not associated with benefits in terms of mortality [relative risk (RR) 0.88, 95% confidence interval (CI) 0.68-1.14, p = 0.33] and RRT dependence (RR 0.81, 95% CI 0.46-1.42, p = 0.46). There were also no significant differences in the ICU and hospital LOS between patients who underwent earlier versus later RRT [standard means difference -0.08 (95% CI -0.26 to 0.09) and -0.11 (95% CI -0.37 to 0.16) day, respectively]. In subgroup analysis, earlier RRT was associated with a reduction in the in-hospital mortality among surgical patients (RR 0.78, 95% CI 0.64-0.96) and patients who underwent continuous renal replacement therapy (CRRT) (RR 0.80, 95% CI 0.67-0.96).
  
  
  CONCLUSIONS
  Compared with later RRT, earlier initiation of RRT did not show beneficial impacts on patient outcomes. However, a lower rate of death was observed among surgical patients and in those who underwent CRRT. The included literature is highly heterogeneous and, therefore, potentially subject to bias. Further high-quality RCT studies are warranted.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital Bei-Hu Branch, No. 87, Neijiang St, Taipei, 108, Taiwan.|Community and Geriatric Research Center, National Taiwan University Hospital Bei-Hu Branch, No. 87, Neijiang St, Taipei, 108, Taiwan.
authors.forename: Tai-Shuan
authors.initials: TS
authors.lastname: Lai
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Saint Marys Hospital Luodong, No. 160, Zhongheng S. Rd., Luodong, Yilan, 26546, Taiwan, ROC.|Saint Mary's Medicine, Nursing and Management College, No. 100, Ln. 265, Sec. 2, Sanxing Rd., Sanxing Township, Yilan County, 266, Taiwan, ROC.
authors.forename: Chih-Chung
authors.identifier: http://orcid.org/0000-0003-2220-7574
authors.initials: CC
authors.lastname: Shiao
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Chi-Mei Medical Center, Liouying. No. 201, Taikang, Taikang Vil., Liuying Dist.736, Tainan City, Taiwan.
authors.forename: Jian-Jhong
authors.initials: JJ
authors.lastname: Wang
authors.affiliation: Division of Internal and Critical Care Medicine, Department of Critical Care Medicine, Taichung Veterans General Hospital, No. 1650 Taiwan Boulevard Sect. 4, Taichung, 40705, Taiwan.
authors.forename: Chun-Te
authors.initials: CT
authors.lastname: Huang
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Mackay Memorial Hospital, No. 92, Sec. 2, Zhongshan N. Rd., Taipei, 10449, Taiwan.
authors.forename: Pei-Chen
authors.initials: PC
authors.lastname: Wu
authors.affiliation: Case Western Reserve University, No. 10900 Euclid Ave., Cleveland, OH, 44106, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Chueh
authors.affiliation: Cleveland Clinic Lerner College of Medicine and Glickman Urological and Kidney Institute, Cleveland Clinic, No. 9980, Carnegie Ave, Cleveland, OH, 44195, USA.
authors.forename: Shih-Chieh Jeff
authors.initials: SJ
authors.lastname: Chueh
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, No. 200 First St. SW, Rochester, MN, 55905, USA. kashani.kianoush@mayo.edu.|Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, No. 200 First St. SW, Rochester, MN, 55905, USA. kashani.kianoush@mayo.edu.
authors.forename: Kianoush
authors.initials: K
authors.lastname: Kashani
authors.affiliation: Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, No. 7 Chung-Shan South Road, Zhong-Zheng District, Taipei, 100, Taiwan. q91421028@ntu.edu.tw.|National Taiwan University Study Group on Acute Renal Failure (NSARF), Taipei, Taiwan. q91421028@ntu.edu.tw.
authors.forename: Vin-Cent
authors.initials: VC
authors.lastname: Wu
keywords: Acute kidney injury; CAKS; Length of stay; Meta-analysis; Mortality; NSARF; Renal replacement therapy; Timing