***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: In patients with severe acute kidney injury ( AKI ) but no urgent indication for renal replacement therapy ( RRT ) , the optimal time to initiate RRT remains controversial . While starting RRT preemptively may have benefits , this may expose patients to unnecessary RRT . To study this , we conducted a 12-center open-label pilot trial of critically ill adults with volume replete severe AKI . Patients were r and omized to accelerated ( 12 h or less from eligibility ) or st and ard RRT initiation .  Outcomes were adherence to protocol -defined time windows for RRT initiation ( primary ) , proportion of eligible patients enrolled , follow-up to 90 days , and safety in 101 fully eligible patients ( 57 with sepsis ) with a mean age of 63 years . Median serum creatinine and urine output  at enrollment were 268 micromoles/l and 356 ml per 24 h , respectively . In the accelerated arm , all patients commenced RRT and 45/48 did so within 12 h from eligibility ( median 7.4 h ) . In the st and ard arm , 33 patients started RRT at a median of 31.6 h from eligibility , of which 19 did not receive RRT ( 6 died and 13 recovered kidney function ) . Clinical outcomes were available for all patients at 90 days following enrollment , with mortality 38 % in the accelerated and 37 % in the st and ard arm . Two surviving patients , both r and omized to st and ard RRT initiation , were still RRT dependent at day 90 . No safety signal was evident in either arm . Our findings can inform the design of a large-scale effectiveness r and omized control trial Background Acute kidney injury is a common and devastating complication of critical illness , for which renal replacement therapy is frequently needed to manage severe cases . While a recent systematic review suggested that “ earlier ” initiation of renal replacement therapy improves survival , completed trials are limited due to small size , single-centre status , and use of variable definitions to define “ early ” renal replacement therapy initiation . Methods / design This is an open-label pilot r and omized controlled trial . One hundred critically ill patients with severe acute kidney injury will be r and omly allocated 1:1 to receive “ accelerated ” initiation of renal replacement therapy or “ st and ard ” initiation at 12 centers across Canada . In the accelerated arm , participants will have a venous catheter placed and renal replacement therapy will be initiated within 12 hours of fulfilling eligibility . In the st and ard initiation arm , participants will be monitored over 7 days to identify indications for renal replacement therapy . For participants in the st and ard arm with persistent acute kidney injury , defined as a serum creatinine not declining > 50 % from the value at the time of eligibility , the initiation of RRT will be discouraged unless one or more of the following criteria are fulfilled : serum potassium ≥6.0 mmol/L ; serum bicarbonate ≤10 mmol/L ; severe respiratory failure ( PaO2/FiO2<200 ) or persisting acute kidney injury for ≥72 hours after fulfilling eligibility . The inclusion criteria are design ed to identify a population of critically ill adults with severe acute kidney injury who are likely to need renal replacement therapy during their hospitalization , but not immediately . The primary outcome is protocol adherence ( > 90 % ) . Secondary outcomes include measures of feasibility ( proportion of eligible patients enrolled in the trial , proportion of enrolled patients followed to 90 days for assessment of vital status and the need for renal replacement therapy ) and safety ( occurrence of adverse events ) . Discussion The optimal timing of renal replacement therapy initiation in patients with severe acute kidney injury remains uncertain , representing an important knowledge gap and a priority for high- quality research . This pilot trial is necessary to establish protocol feasibility , confirm the safety of participants and obtain estimated events rates for design of a large definitive trial . Trial registration Objective : The impact of continuous venovenous hemofiltration on  sepsis-induced multiple organ failure  severity is controversial . We sought to assess the effect of early application of hemofiltration on the degree of organ dysfunction and plasma cytokine levels in patients with severe sepsis or septic shock . Design : Prospect i ve , r and omized , open , multicenter study setting , 12 French intensive care units . Patients : A total of 80 patients were enrolled within 24 hours of development of the first organ failure related to a new septic insult . Interventions : Patients were r and omized to group 1 ( HF ) , who received hemofiltration ( 25 mL/kg/hr ) for a 96-hour period , or group 2 ( C ) who  were managed conventionally . Measurements and Main Results : The primary end point was the number , severity , and duration of organ failures during 14 days , as evaluated by the Sepsis-Related Organ Failure Assessment score , on an intention-to-treat analysis . Strict guidelines were provided to perform continuous hemofiltration under the same conditions and bearing the same objectives in all centers . Because of inclusion stagnation , the trial was discontinued after an interim analysis by which time 76 patients had been r and omized . The number and severity of organ failures were significantly higher in the HF group ( p < 0.05 ) . No modifications in plasma cytokine levels could be detected . Conclusion : These data suggest that early application of st and ard continuous venovenous hemofiltration is deleterious in severe sepsis and septic shock . This study does not rule out an effect of high-volume hemofiltration ( > 35 mL/kg/hr ) on the course of sepsis BACKGROUND The timing of renal-replacement therapy in critically ill patients who have acute kidney injury but no potentially life-threatening complication directly related to renal failure is a subject of debate . METHODS In this multicenter r and omized trial , we assigned patients with severe acute kidney injury ( Kidney Disease : Improving Global Outcomes [ KDIGO ] classification , stage 3 [ stages range from 1 to 3 , with higher stages indicating more severe kidney injury ] ) who required mechanical ventilation , catecholamine infusion , or both and did not have a potentially life-threatening complication directly related to renal failure to either an  early or a delayed strategy of renal-replacement therapy .  With the early strategy , renal-replacement therapy was started immediately after r and omization . With the delayed strategy , renal-replacement therapy was initiated if at least one of the following criteria was met : severe hyperkalemia , metabolic acidosis , pulmonary edema , blood urea nitrogen level higher than 112 mg per deciliter , or oliguria for more than 72 hours after r and omization . The primary outcome was overall survival at day 60 . RESULTS A total of 620 patients underwent r and omization . The Kaplan-Meier estimates of mortality at day 60 did not differ significantly between the early and delayed strategies ; 150 deaths occurred among 311 patients in the early- strategy group ( 48.5 % ; 95 % confidence interval [ CI ] , 42.6 to 53.8 ) , and 153 deaths occurred among 308 patients in the delayed- strategy group ( 49.7 % , 95 % CI , 43.8 to 55.0 ; P=0.79 ) . A total of 151 patients ( 49 % ) in the delayed- strategy group did not receive renal-replacement therapy . The rate of catheter-related bloodstream infections was higher in the early- strategy group than in the delayed- strategy group ( 10 % vs. 5 % , P=0.03 ) . Diuresis , a marker of improved kidney function , occurred earlier in the delayed- strategy group ( P<0.001 ) . CONCLUSIONS In a trial involving critically ill patients with severe acute kidney injury , we found no significant difference with regard to mortality between an early and a delayed strategy for the initiation of renal-replacement therapy . A delayed strategy averted the need for renal-replacement therapy in an appreciable number of patients . ( Funded by the French Ministry of Health ; Clinical Trials.gov number , NCT01932190 . ) BACKGROUND Optimum timing of the initiation of dialysis therapy in acute kidney injury is not clear . STUDY DESIGN Prospect i ve , open label , 2-arm , r and omized , controlled trial . SETTING & PARTICIPANTS 208 adults with acute kidney injury with progressively worsening azotemia at the artificial kidney dialysis unit of a tertiary-care referral center in western India . INTERVENTION Earlier-start dialysis was initiated when serum urea nitrogen and /or creatinine levels increased to 70 and 7 mg/dL , respectively , whereas the usual-start dialysis patients ( control group ) received dialysis when clinical ly indicated as judged by treating nephrologists . OUTCOMES Primary outcome was in-hospital mortality and dialysis dependence at 3 months . Secondary outcome in patients receiving dialysis was time to recovery of kidney function , computed from time of enrollment to the last dialysis session . RESULTS Of 585 screened patients , 102 were assigned to earlier-start dialysis , and 106 to usual-start dialysis . Baseline characteristics were similar between r and omized groups . 93 ( 91.1 % ) and 88 ( 83.1 % ) participants received dialysis in the intervention and control groups , respectively . Mean serum urea nitrogen and serum creatinine levels at dialysis therapy initiation were 71.7 ± 21.7 ( SD ) and 7.4 ± 5.3 mg/dL , respectively , in the intervention group versus 100.9 ± 32.6 and 10.41 ± 3.3 mg/dL in the control group . Data on primary outcome were available for all patients . In-hospital mortality was 20.5 % and 12.2 % in the intervention and control groups , respectively ( relative risk , 1.67 ; 95 % CI , 0.88 - 3.17 ; P = 0.2 ) . 4.9 % and 4.7 % of patients in the intervention and control groups , respectively , were dialysis dependent at 3 months ( relative risk , 1.04 ; 95 % CI , 0.29 - 3.7 ; P = 0.9 ) . LIMITATIONS Study was not double blind , event rate ( ie , mortality ) was less than predicted , wide CIs preclude definitive findings . CONCLUSIONS Our data do not support the earlier initiation of dialysis therapy  in community-acquired acute kidney injury Objective To study the effects of the initiation time of continuous venovenous hemofiltration and of the ultrafiltrate rate in patients with circulatory and respiratory insufficiency developing early oliguric acute renal failure . The primary end points were mortality at 28 days and recovery of renal function . Design A r and omized , controlled , two-center study . Setting The closed-format multidisciplinary intensive care units of a university hospital ( 30 beds ) and a teaching hospital ( 18 beds ) . Patients and Interventions A total of 106 ventilated severely ill patients who were oliguric despite massive fluid resuscitation , inotropic support , and high-dose intravenous diuretics were r and omized into three groups . Thirty-five patients were treated with early high-volume hemofiltration ( 72–96 L per 24 hrs ) , 35 patients with early low-volume hemofiltration ( 24–36 L per 24 hrs ) , and 36 patients with late low-volume hemofiltration ( 24–36 L per 24 hrs ) . Results Median ultrafiltrate rate was 48.2 ( 42.3–58.7 ) mL·kg−1·hr−1 in early high-volume hemofiltration , 20.1 ( 17.5–22.0 ) mL·kg−1·hr−1 in early low-volume hemofiltration , and 19.0 ( 16.6–21.1 ) mL·kg−1·hr−1 in late low-volume hemofiltration . Survival at day 28 was 74.3 % in early high-volume hemofiltration , 68.8 % in early low-volume hemofiltration , and 75.0 % in late low-volume hemofiltration ( p = .80 ) . On average , hemofiltration started 7 hrs after inclusion in the early groups and 42 hrs after inclusion in the late group . All hospital survivors had recovery of renal function at hospital discharge , except for one patient in the early low-volume hemofiltration group . Median duration of renal failure in hospital survivors was 4.3 ( 1.4–7.8 ) days in early high-volume hemofiltration , 3.2 ( 2.4–5.4 ) days in early low-volume hemofiltration , and 5.6 ( 3.1–8.5 ) days in late low-volume hemofiltration ( p = .25 ) . Conclusions In the present study of critically ill patients with oliguric acute renal failure , survival at 28 days and recovery of renal function were not improved using high ultrafiltrate volumes or early initiation of hemofiltration IMPORTANCE Optimal timing of initiation of renal replacement therapy ( RRT ) for severe acute kidney injury ( AKI ) but without life-threatening indications is still unknown . OBJECTIVE To determine whether early initiation of RRT in patients who are critically ill with AKI reduces 90-day 
    Output:
    
Early RRT in patients with AKI ( or at risk for AKI ) does not appear to provide a significant reduction in mortality rates compared with late RRT .
The data did not suggest any apparent impact on renal recovery with early dialysis