Table 1.

Study characteristics.

Study	Setting/patient group	Inclusion criteria	Numbers	RRT modality	Early definition for RRT	Late definition for RRT	Outcomes
Pursnani et al.27	Single centre; all inpatients; medical only	Diagnosis of acute tubular necrosis with serum creatinine <7 mg% and blood urea <120 mg%	Total = 35 Early = 18 Late = 17	IHD	Early hemodialysis (as soon as met eligibility criteria)	Conservative management	Overall mortality Length of hospital stay Adverse events
Bouman et al.28,a	Two centres, single country; ICU only; mixed patients	Urine output <30 ml/h for >6 h and creatinine clearance <20 ml/min	Total = 106 Early = 70 Late = 36	CRRT	RRT started within 12 h of inclusion	Plasma Urea level >40 mmol/l, potassium >6.5 mmol/l or severe pulmonary oedema	ICU, hospital and 28-day mortality Recovery of renal function at 90 days Duration of ICU and hospital stay Adverse events
Sugahara and Suzuki29	Single centre; ICU only; surgical only	Post-CABG patients. Hourly urine output <30 ml/h and serum creatinine increased at rate of 0.5 mg/dl/day or more	Total = 28 Early = 14 Late = 14	CRRT	Urine output <30 ml/h for three consecutive hours (or daily urinary output 750 ml or less)	Urine output <20 ml/h for two consecutive hours (or daily urinary output 500 ml or less)	14-day mortality Changes in BP, urine output and creatinine
Jamale et al.30	Single centre; all inpatients; medical only	Severe AKI with increasing serum urea and creatinine levels	Total = 208 Early = 102 Late = 106	IHD	Serum urea >70 mg/dl and/or creatinine level >7 mg/dl	Treatment refractory hyperkalaemia, volume overload, acidosis. Uremic nausea and anorexia with inability to maintain oral intake	In hospital mortality Dialysis dependence at 90 days Number of RRT days Adverse events
Wald et al.31	Multiple centres, single country; ICU only; mixed patients	Volume repletes severe AKI with two criteria from three: creatinine doubled from baseline, urine output <6 ml/kg in last 12 h or whole blood NGAL >400 ng/ml. Absence of urgent indications for RRT.	Total = 100 Early = 48 Late = 52	Mixed	RRT started within 12 h of fulfilling eligibility criteria	Potassium >6.0 mmol/l, serum bicarbonate <10 mmol/l, PaO2/FiO2 <200 with infiltrates on chest radiograph suggestive of pulmonary oedema	ICU, hospital and 90-day mortality Dialysis dependence at 90 days Length of ICU and hospital stay Adverse events
Gaudry et al.13	Multiple centres, single country; ICU only; mixed patients	KDIGO3 stage 3 AKI compatible with a diagnosis of ischaemic or toxic acute tubular necrosis and receiving mechanical ventilation and/or catecholamine infusion.	Total = 619 Early = 311 Late = 308	Mixed	RRT commenced within 6 h after documentation of KDIGO3 stage 3 AKI	Urea >40 mmol/l, potassium >6 mmol/l (or >5.5 mmol/l despite medical treatment), pH <7.15, pulmonary oedema due to fluid overload requiring oxygen >5 l/ or FiO2 >50%, oliguria or anuria >72 h	28- and 60-day mortality Dialysis dependence at 28 and 60 days Length of ICU and hospital stay Number of RRT, mechanical ventilation and vasopressor free days
Zarbock et al.14	Single centre; ICU only; mixed patients	KDIGO stage 2 AKI (baseline creatinine doubled or urinary output <0.5 ml/kg/h for >12 h) despite optimal resuscitation, NGAL >150 ng/ml and one of: severe sepsis, use of vasopressors, refractory fluid overload and progression of non-renal organ dysfunction	Total = 231 Early = 112 Late = 119	Mixed	RRT started within 8 h of diagnosis of KDIGO stage 2 AKI	Commenced within 12 h of diagnosis of stage 3 AKI, or if urea >100 mg/dL, potassium >6.0 mmol/l and or ECG changes, urine output <200 ml in 12 h or organ oedema resistant to diuretic treatment	28-, 60- and 90-day mortality Dialysis dependence at 28, 60 and 90 days Length of ICU and hospital stay Length of mechanical ventilation and RRT Adverse events
Srisawat et al.20,b	Single centre; ICU only; mixed patients	Patients aged 18 or older diagnosed with AKI by RIFLE criteria1	Total = 40 Early = 20 Late = 20	CRRT	RRT started within 12 h of randomization	Severe refractory acidosis (pH < 7.2 or HCO3 <15), severe peripheral oedema, pulmonary oedema, no response to diuretics, refractory hyperkalaemia (K > 6.2 or ECG changes), anuria or oliguria or high BUN (>60)	28-day mortality Dialysis dependence at 28 days Mechanical ventilation free days ICU-free days Renal recovery at 28 days Balance of input and output fluid
Lumlertgul et al.21,c	Multiple centres, single country; ICU only; mixed patients	AKI with diagnosis of Acute Tubular Necrosis, clinically resuscitated and euvolaemic, no urgent indication or contraindications for RRT.	Total = 118 Early = 58 Late = 60	CRRT	RRT was started in the early group within 6 h of randomisation	Urea >100 mg/dl, potassium >6 mmol/l, serum bicarbonate <12 mmol/l, pH <7.15, PaO2/FiO2 ratio <200 or chest radiographs compatible with pulmonary oedema	28-day mortality Dialysis dependence and renal recovery at 28 days Length of ICU and hospital stay Number of RRT and mechanical ventilation-free days
Barbar et al.22	Multiple centres, single country; ICU only; mixed patients	Early phase of septic shock (within 48 h of start of vasopressor therapy) developing AKI with at least one criterion of the failure stage of the RIFLE classification system1	Total = 488 Early = 246 Late = 242	Mixed	RRT commenced within 12 h of documentation of ‘failure’ stage AKI1	RRT commenced 48 h after diagnosis of AKI or if prior to this: serum potassium >6.5 mmol/l, pH <7.15 or fluid overload with pulmonary oedema	28, 90 and 180 day mortality Dialysis dependence at 28 and 90 days Length of ICU and hospital stay RRT, mechanical ventilation and vasopressor-free days Adverse events

AKI: acute kidney injury; BUN: blood urea nitrogen; CABG: coronary artery bypass graft; CRRT: continuous renal replacement therapy; ECG: electrocardiogram; ICU: intensive care unit; IHD: ischaemic heart disease; KDIGO: kidney disease improving global outcomes; NGAL: neutrophil gelatinase-associated lipocalin; RIFLE: isk, injury, failure, loss, end-stage kidney disease; RRT: renal replacement therapy.

^aPatients in early group split into low-volume (n = 35) and high-volume (n = 35) hemofiltration.

^bPatients were tested for plasma neutrophil gelatinase associated lipocalin (pNGAL) levels after recruitment. Patients with pNGAL level greater than or equal to 400ng/ml were randomized into early or late groups.

^cPatients underwent a furosemide stress test first. If they were non-responsive they were randomised into early or late groups.