ELAIN 2016.

Study characteristics
Methods	Study design: parallel, open‐label RCT Duration of study: August 2013 to July 2015 Duration of follow‐up: 90 days
Participants	Setting: single centre Country: Germany Critically ill patients ≥ 18 years with AKI stage 2 (2‐fold increase in SCr from baseline or urinary output < 0.5 mL/kg ≥ 12 hours) despite optimal resuscitation; plasma NGAL > 150 ng/mL Number: intervention group (112); control group (119) Mean age ± SD (years): intervention group (65.7 ± 13.5); control (68.2 ± 12.7) Sex (M/F): intervention group (78/34); control (68/51) Exclusion criteria: pre‐existing CKD (GFR < 30 mL/min) previous KRT; AKI caused by permanent occlusion or surgical lesion of the renal artery; GN; interstitial nephritis or vasculitis; AKI caused by postrenal obstruction or haemolytic uraemic syndrome or thrombocytopenic purpura; pregnancy; prior kidney transplantation; hepatorenal syndrome; AIDS with a CD4 count of < 0.05 x 10 E/L; haematological malignancy with neutrophils < 0.05 x 10 E/L; non‐HF machine‐free for use at the moment of inclusion; participation in another interventional clinical study
Interventions	KRT modality CVVHDF Replacement fluid: pre‐dilution mode Regional anticoagulation with citrate Intervention group Early initiation of CKRT: intervention was started within 8 hours of diagnosis of stage 2 of the KDIGO classification (urine output < 0.5 mL/kg/hour for ≥ 12 hours or 2‐fold increase in SCr compared with baseline) Control group Delayed initiation of CKRT: intervention started within 12 hours of stage 3 of the KDIGO classification (urine output < 0.3 mL/kg/hour for ≥ 24 hours and or 3‐fold increase in SCr compared with baseline) Co‐interventions Not reported
Outcomes	Primary outcomes Death at 90 days Secondary outcomes Death at day 28 and 60 Clinical evidence of organ dysfunction (daily SOFA score) Recovery of kidney function ICU and hospital length of stay Markers of inflammation (IL6, IL8, IL10, IL18, and macrophage migration inhibitory factor)
Notes	Funding source: Else‐Kroner Fresenius Stiftung (2013_A46 to A.Z.)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Patients were randomly assigned using computer‐generated method
Allocation concealment (selection bias)	Low risk	Each patient received a study identification number and treatment allocation at enrolment
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Insufficient information to permit judgement (for kidney recovery was unclear risk but for death was low risk)
Blinding of outcome assessment (detection bias) All outcomes	Low risk	The outcome measurement unlikely to be influenced by lack of blinding
Incomplete outcome data (attrition bias) All outcomes	Low risk	Complete outcome data were reported
Selective reporting (reporting bias)	Low risk	The study reported death, kidney function recovery and adverse events
Other bias	Low risk	Quote: "The study sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication"