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Table 1 Characteristics of the included studies

From: Early versus late initiation of renal replacement therapy in patients with acute kidney injury-a systematic review & meta-analysis of randomized controlled trials

Study author Setting, Country Participants Intervention Outcomes measured Comments
Pursnani 1997 [18] India Number: 35 (Early RRT = 18; Late RRT = 17
Age: Adults
Inclusion criterion: cases of acute tubular necrosis with creatinine <7 mg% and blood urea <120 mg%
Exclusion criterion: cases with creatinine >7 mg% and urea blood urea >120 mg%.
Early RRT = Prophylactic hemodialysis was performed
Late RRT = Conservatively managed
Mortality, complications and hospital stay Method of randomization not given. Blinding and allocation concealment not clear. Small sample size
Bouman 2002 [7] Two Centres
(Intensive care unit),
Number: 106 patients (Early RRT = 70; late RRT = 36
Age: 18-90 years
Inclusion: Critically ill patients with circulatory and respiratory failure, developing early oliguric ARF,
Exclusion: Pre-existing renal disease
Early RRT = Hemofiltration started within 12 h of inclusion
Late RRT = Hemofiltration started when patient fulfilled conventional criterion for renal replacement therapy such as plasma urea level of 40 mmol/L, potassium of 6.5 mmol/L or severe pulmonary edema.,
Survival at day 28 after inclusion and recovery of renal function, ICU survival, hospital survival, duration of mechanical ventilation, length of ICU stay, and length of hospitalization. Open label. Allocation concealment not clear. Three treatment strategies were compared viz early high volume hemofiltration, early low volume hemofiltration and late low volume hemofiltration. Small sample size.
Durmaz 2003 [16] Single centre (In-patients undergoing coronary artery bypass surgery)
Number: 44 (Early RRT = 21;Late RRT = 23
Age: Adult patients
Inclusion: Post cardiac surgery
Exclusion: Age less than 18 years; chronic dialysis
Early RRT = Pre-operative prophylactic hemodialysis was performed if serum creatinine ≥2.5 mg/dl
Late RRT = Hemodialysis was performed only if postoperative acute renal failure was seen (defined as urine output of less than 400 mL in a 24-h period, a 50% increase in serum creatinine from base line, or need for dialysis).
Overall 30 day mortality; mean decrease in serum creatinine, potassium and BUN levels; average length of stay in cardiac ICU, average length of postoperative in-hospital stay. Quasi randomized trial.
Small sample size.
Sugahara 2004 [19] Single Centre (in-patient)
Number: 28 (Early RRT = 14; Late RRT = 14)
Age Adults:
Inclusion: Post cardiac surgery
Exclusion: Pregnancy, Bilirubin >5 mg/dl, mental disorders, Cancer, Early recovery of urine output i.e >30 ml/kg prior to RRT
Early RRT = Dialys started if ourly urine output <30 ml/kg for 3 h or daily urine output ≤750 ml .
Late RRT = Dialysis started if hourly urine output <20 ml/kg for 2 consecutive hours or daily urine output ≤500 ml.
Overall 14 days mortality, changes in the blood pressure, changes in serum creatinine, changes in urine output. Open label randomized controlled trial. Allocation concealment not clear. Small sample size.
Payen 2009 [5] Multicentric
(Intensive care units), France
Number: 76 (Early RRT = 37;Control group = 39
Age: Adult patients
Inclusion: Multisystem/severe sepsis.
Early RRT = Hemofiltration started if, clinically identified focus on infection associated with at least 2 systemic inflammatory response syndrome criteria and one or more sepsis-induced organ failures within the 24 h before inclusion, plus a Simplified Acute Physiology II score between 35 and 63.
Control group = standard therapy
Overall 28 day mortality; occurrence or worsening of sepsis induced organ failure (SOFA score), length of ICU stay, duration of mechanical ventilation, ionotropic support,,measurement s of cytokines, adverse events. Open label. Allocation concealment unclear. Authors concluded that in septic patients, hemofiltration with an ultrafiltration rate of 2 L/h did not limit organ failure
Jamale 2013 [6] Single centre
(Intensive care unit),
Number: 208 (Early RRT = 102;late RRT = 106)
Age: Adult patients
Inclusion: Patients with severe community acquired AKI with increasing serum urea nitrogen and creatinine levels.
Exclusion: Requirement of urgent dialysis for life-threatening uremic complications (ie, treatment-refractory hyperkalemia and fluid overload, alteration of higher mental function attributable to uremia, and pericarditis), patients who received dialysis therapy before evaluation, and who were judged to be in the recovery phase.
Early RRT = initiation of dialysis therapy if serum urea nitrogen level increased to >70 mg/dL and/or creatinine level increased to >7 mg/dL irrespective of complications till recovery of renal functions.
Late RRT = Dialysis therapy was initiated only if participants developed complications such as treatment-refractory hyperkalemia, volume overload, and acidosis, uremic nausea and anorexia leading to inability to maintain nutrient intake until recovery
Overall 3 months mortality, Dialysis dependence at 3 months, increase in urine output, decrease in blood urea nitrogen and creatinine, days to renal recovery, adverse events such as bleeding, number of catheter related complications including infections, number of episodes of intradialytic hypotension, requirement of blood products for transfusion, Open label trial. Event rate (mortality) was less than predicted. Study population included community acquired AKI (different from usual AKI population). Use of intermittent dialysis (not continuous) as a modality of RRT.
Combes 2015 [15] Multicentric
(Postoperative ICU)
Number = 224 (Early RRT = 112; Late RRT/standard care = 112)
Age: Adult patients
Inclusion criterion: Post cardiac surgery with persistent postoperative shock requiring high dose catecholamines within 24 h following surgery.
Exclusion criterion: Younger than 18 years old; pregnant; previously enrolled in this or other trials evaluating mortality; on chronic hemodialysis prior to heart surgery; weight greater than 120 kg; moribund state (defined as Simplified Acute Physiology Score (SAPS) II greater than 90); or those for whom active therapeutics were withheld or withdrawn.
Early RRT = High volume hemofiltration for 48 h followed by standard-volume continuous venovenous hemodiafiltration (CVVHD) till recovery of renal function.
Late RRT/control group = Supportive management was provided and CVVHDF (CVVHDF (if serum creatinine >4 mg/dl] or threefold increase of preoperative values, or urine output < 0.3 ml/kg/h for 24 h despite adequate fluid resuscitation; serum urea > 36 mmol/L, or life-threatening hyperkalemia).
Overall mortality on day 30, day 60 and day 90, ICU and hospital length of stay; Day 30 duration of catecholamine infusion, RRT and mechanical ventilation; numbers of catecholamine, RRT and mechanical ventilation free days; Sequential Organ Failure Assessment (SOFA) score until Day 30, percentage of patients with renal recovery and adverse events. Open label trial. Allocation concealment not done. Trail was prematurely terminated after only 2/3rd of the calculated enrollments. Only post cardiac surgery patients were enrolled.
Wald 2015 [17] Multicentric (Intensive care unit)
Number = 101 (Early RRT group = 48; Late RRT/control group = 52)
Age : Adult patients
Inclusion criterion: presence of severe AKI (defined by the presence of two of the following three criteria: (i) a twofold increase in serum creatinine from baseline, (ii) urine output 0.6 ml/kg in the preceding 12 h, or (iii) whole-blood NGAL ≥ 400 ng/ml); [2] the absence of urgent indications for RRT initiation (defined as serum potassium ≤ 5.5 mmol/l and serum bicarbonate ≥ 15 mmol/l); and [3] low likelihood of volume-responsive AKI (defined as central venous pressure ≥ 8 mm Hg).
Exclusion criterion: Lack of commitment to ongoing life support, including RRT; presence of an intoxication requiring extracorporeal removal; RRT within the previous 2 months; clinical suspicion of renal obstruction, rapidly progressive glomerulonephritis, or interstitial nephritis; pre-hospitalization estimated glomerular filtration rate o 30 ml/min per 1.73 m2; and the passage of 4 48 h since doubling of baseline serum creatinine.
Early RRT = patients that fulfilled inclusion criterion were started RRT modality based on current best practice guidelines till death, recovery of renal functions or changes in goals of care.
Late RRT/Control group = Supportive management was provided and RRT initiated once following condition developed:
Serum potassium > 6.0 mmol/l, serum bicarbonate < 10 mmol/l, or PaO2/ FiO2 < 200 with infiltrates on chest radiograph compatible with pulmonary edema. RRT was to continue until patient death, change in goals of care, or recovery of kidney function. Modality selection was based on physicians discretion (IDH, SLED or CRRT).
Proportion of patients in each arm who commenced RRT within the protocol-specified window (≤12 and 4 12 h), the proportion of patients successfully consented among those fully eligible (feasibility target ≥ 50%),the proportion of patients followed to day 90 (feasibility target ≥ 95%), and serious adverse events. Open label, parallel feasibility randomized controlled trial. Allocation concealment not clear. Small sample size
Gaudry 2016 [8] Multi-centric
(Intensive care units)
Number: 620 (Early RRT = 312; Late RRT/control group = 308)
Age: Adult patients
Inclusion criterion: Patient with severe acute kidney injury (KDIGO stage 3) requiring mechanical ventilation, catecholamine infusion or both and did not have potentially life threatening complications directly related to renal failure.
Exclusion criterion: Age <18 years, a blood urea nitrogen level >112 mg per deciliter (40 mmol per liter), a serum potassium concentration > 6 mmol per liter (or greater than 5.5 mmol per liter despite medical treatment), a pH <7.15 in the context of either pure metabolic acidosis (partial pressure of arterial carbon dioxide [Pa co2] below 35 mm Hg) or mixed acidosis (Pa co2 of 50 mm Hg or more without the possibility of increasing alveolar ventilation), and acute pulmonary edema due to fluid overload responsible for severe hypoxemia requiring an oxygen flow rate greater than 5 l per minute to maintain a peripheral capillary oxygen saturation (Sp o2) greater than 95% or requiring a fraction of inspired oxygen (F io2) greater than 50% in patients receiving mechanical ventilation and despite diuretic therapy.
Early RRT = RRT started as soon as possible after randomization in order for it to be started within 6 h of documentation of stage 3 AKI.
Late RRT = Renal-replacement therapy was initiated if one of the laboratory abnormalities defined in the exclusion criterion developed or if oliguria or anuria lasted for more than 72 h after randomization.
The choice of the method of renal-replacement therapy (intermittent or continuous technique, duration and interval between sessions, device setting, and anticoagulation method) was left to the discretion of each study site and was prescribed and monitored according to national guidelines.
Overall mortality on day 60, receipt of renal-replacement therapy at least once with the delayed strategy; numbers of renal-replacement therapy–free days, dialysis catheter–free days, mechanical ventilation–free days, and vasopressor therapy–free days on day 28, Sepsis-related Organ Failure Assessment (SOFA) score at day 3 and day 7; the vital status at day 28; the length of stay in the intensive care unit and in the hospital; the proportion of patients with treatment limitations; the occurrence of nosocomial infections; and complications potentially related to acute kidney injury or renal replacement therapy. Open label trial. Inadequate sample size..The patients in the trial have advance acute kidney injury i.e KDIGO stage 3 reducing generalizability of the study among different staging.
Zarbock 2016 [9] Single centre (Intensive care unit)
Number = 2319 (Early RRT = 112; Late RRT/control group = 119)
Age: 18-90 years.
Inclusion criterion: critically ill patients with AKI Kidney Disease: Improving Global Outcomes (KDIGO) stage 2 (2 times baseline or urinary output <0.5 mL/kg/h for 12 h) and plasma neutrophil gelatinase–associated lipocalin level higher than 150 ng/m.
Exclusion criterion:
Early RRT: Continuous venovenous hemodiafiltration was initiated within 8 h of diagnosis of stage 2 AKI using KDIGO classification.
Late RRT: Continuous venovenous hemodiafiltration was initiated within 12 h of diagnosing stage 3 AKI by KDIGO criterion or if any of the following absolute indications for RRT were present: serum urea level higher than 100 mg/dL; serum potassium level higher than 6 mEq/L and/or with electrocardiography abnormalities; serum magnesium level higher than 8 mEq/L (to convert to mmol/L, multiply by 0.5); urine production lower than 200 mL per 12 h or anuria (according to the KDIGO recommendations); and organ edema in the presence of AKI resistant to diuretic treatment.
Overall mortality on day 90, mortality on day 28 and day 60,clinical evidence of organ dysfunction determined by SOFA scores, recovery of renal functions, requirement of hemodialysis after day 28 and 60, duration of renal support, ICU and hospital length of stay and markers of inflammation. Open label trial. Allocation concealment not clear. Limited generalizability as almost all patients recruited were surgical patients. Authors proposed that adequately powered multicenter trial is needed to confirm our results and establish the best time point for the initiation of RRT in critically ill patients with AKI.