title: Early versus late initiation of renal replacement therapy in patients with acute kidney injury-a systematic review & meta-analysis of randomized controlled trials.
abstract: BACKGROUND
  Acute kidney injury (AKI) is a common complication in the critically ill patients and associated with a substantial morbidity and mortality. Severe AKI may be associated with up to 60% hospital mortality. Over the years, renal replacement therapy (RRT) has emerged as the mainstay of the treatment for AKI. However, the exact timing of initiation of RRT for better patient outcome is still debatable with conflicting data from randomized controlled trials. Thus, a systematic review and meta-analysis was performed to assess the impact of "early" versus "late" initiation of RRT.
  
  
  METHODS
  All the published literature through the major databases including Medline/Pubmed, Embase, and Google Scholar were searched from 1970 to October 2016. Reference lists from the articles were reviewed to identify additional pertinent articles. Retrieved papers concerning the effect of "early/prophylactic" RRT versus "late/as and when required" RRT were reviewed by the authors, and the data were extracted using a standardized data collection tool. Randomized trials (RCTs) comparing early initiation of RRT or prophylactic RRT with late or as and when required RRT were included. The primary outcome measures were all cause mortality and dialysis dependence on day 90. The secondary outcome measures were: length of ICU stay, length of hospital stay, recovery of renal function and adverse events.
  
  
  RESULTS
  Of the 547 citation retrieved, full text of 44 articles was assessed for eligibility. Of these a total of 10 RCTs with 1,636 participants were included. All the trials were open label; six trials have unclear or high risk of bias for allocation concealment while four trials have low risk of bias for allocation concealment. There was a variable definition of early versus late in different studies. Thus, the definition of early or late was taken according to individual study definition. Compared to late RRT, there was no significant benefit of early RRT on day 30 mortality [6 studies; 1301 participants; RR, 0.92;95% CI: 0.76, 1.12); day 60 mortality [3 trials;1075 participants; RR, 0.94; 95% CI: 0.78, 1.14)]; day 90 mortality [3 trials; 555 participants; RR,0.94;95% CI: 0.67, 1.33)]; overall ICU or hospital mortality; dialysis dependence on day 90 [3 trials; (RR, 1.06; 95% CI:0.53, 2.12)]. There was no significant difference between length of ICU or hospital stay or recovery of renal functions. A subgroup analysis based on modality of RRT or mixed medical and surgical vs. surgical or based on severity of illness showed no difference in outcome measure. The trials with high or unclear risk of bias for allocation concealment showed benefit of early RRT (RR, 0.74; 95% CI: 0.59, 0.91) while the trials with low risk of bias for allocation concealment showed no difference in the mortality (RR, 1.02; 95% CI: 0.89, 1.17). Grade evidence generated for most of the outcomes was "low quality".
  
  
  CONCLUSIONS
  This updated meta-analysis showed no added benefit of early initiation of RRT for patients with AKI. The grade evidence generated was of "low quality" and there was a high heterogeneity in the included trials.
  CRD42016043092 .
authors.affiliation: Department of Pediatrics, All India Institute of Medical Sciences (AIIMS), Room no.18, OPD Block, Bhopal, Madhya Pradesh, 462024, India. drgcbhatt@gmail.com.
authors.forename: Girish Chandra
authors.initials: GC
authors.lastname: Bhatt
authors.affiliation: Department of Pediatrics, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, Odisha, India.
authors.forename: Rashmi Ranjan
authors.initials: RR
authors.lastname: Das
mesh_terms: D058186:Acute Kidney Injury / Q000401:mortality* / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D016032:Randomized Controlled Trials as Topic; D017582:Renal Replacement Therapy / Q000401:mortality* / Q000706:statistics & numerical data*; D012307:Risk Factors; D055502:Secondary Prevention / Q000706:statistics & numerical data*; D015996:Survival Rate; D061665:Time-to-Treatment / Q000706:statistics & numerical data*; D016896:Treatment Outcome
keywords: Acute kidney Injury (AKI); Renal replacement therapy (RRT); Timing