2016 RRT trial: ELAIN vs. AKIKI

From 2016 JAMA--ELAIN trial

	NEJM--AKIKI (multicenter)	JAMA--ELAIN trial (single center)
Hypothesis	We hypothesized that the "delayed" strategy would prove beneficial to the patients and would translate into increased survival. The study is designed to prove superiority (and not noninferiority) of this strategy over the "early" one.	We hypothesize that an early initiation of RRT decreases the 90-day mortality from all causes compared to late onset of RRT.
Study population	RIFLE F: early and late (or with alert criteria)	AKIN 2 and 3 (3 or absolute indication)
AKI definition	RIFLE F: early or late	AKIN stage: 2 or 3
Intervention	Arm 1: RRT immediately when a RIFLE F status is documented Arm 2: RRT in patient with RIFLE F only in case of occurrence of one or more of the follow events (“Alert Criteria”)	Arm 1: Early initiation of RRT (AKIN 2) Arm 2: Late initiation of RRT (AKIN 3 or absolute indication for RRT)
Primary outcome	Overall survival, measured from the date of randomization to the date of death, regardless of the cause. Minimun duration: 60-day follow-up	Overall survival in a 90-day follow up period (90-day all cause mortality)
Secondary outcome	survival rate at D28 % of patients requireing who did not require RRT in the delayed strategy timie unitl cessation of RRT therapy Rate of adverse events potentially related to the AKI or to RRT (eg; RRT catheter related complicates, hemorrhage due to anticoagulation required for RRT etc…) rate of nosocomial infections # of vetilator free days of RRT free days and of vasopressors free days length of stay in ICU and hospital rate of limitations of treatment for futiligy total cost of connsumables (including RRT catheters and lines among others) related to RRT between D1 and D28	Length of ICU stay Length of hospitalization Duration of RRT Recovery of renal fx by D28 60-d and 1-yr all cause mortality SOFA score at D1-14,21,28 cost adnlysis of RRT Incidence of complication due to RRT
Inclusion criteria	ICU patients Age > = 18 years AKI compatible with the dx of ATN defined by clinical ischemic or toxi insult AKI, with RIFLE F classification: (one of the following 3) Creatinine > 354 mmol/L (4mg/dL) or > 3 times the baseline anuria for more than 12 hours oliguria defined as U/O < 0.3ml/kg/hr or 500ml/d for more than 24 hours Mechanical ventilation and/or catecholamines infusion (noradrenaline or/and adrenaline)	AKI: AKIN 2 despite optimal resuscitation Plasma NGAL > 150ng/mL at least one of the following conditions severe sepsis, use of catecholamines > 0.1ug/mkg/min, refractory fluid overload, non-renal SOFA> = 2 age 18~90 y/o intention to provide full intensive care tx for at least > 3-d existence of informed consent
Exclusion criteria	CKD (defined as creatinine clearance < 30ml/min) Patients already enrolled in the study Inclusion criteria #4 present for more than 5 hours AKI due to urinary tract obstruction renal vessels obstruciton tumor lysis syndrome thrombotic microangiopathy acute GN Intoxication with a dialyzable product Child-Pugh class C liver cirrhosis Renal transplant Cardiac arrest without awakening at time of potential inclusion Moribund state decision to limit treatment RRT already started for the current episode of AK Presenting (at time of potential inclusion) a strong indication for immediate RRT oligoanuria for more than 3 days Alert criteria Under cardiopulmonary bypass Included in another clinical trial on RRT modalities	pre-exsting kidney dx w/o RRT (GFR < 30 ml/min) p’t w/ previous RRT experience AKI due to permanent occlusion or surgical lesion of the renal artery AKI due to GN, interstitial nephritis, or vasculitis AKI caused by postrenal obstruction HUS/TTP Pregnancy prior kidney Tx HRS AIDS w/ CD4 < 50/uL hema malig. w/ ANC < 50/uL no HF machine free for use at the moment of inclusion
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 strat- egy for the initiation of renal-replacement therapy. A delayed strategy averted the need for renal-replacement therapy in an appreciable number of patients.	AmongcriticallyillpatientswithAKI,early RRT compared with delayed initiation of RRT reduced mortality over the first 90 days. Further multicenter trials of this intervention are warranted.