This document discusses early initiation of renal replacement therapy (RRT) compared to late or delayed initiation in patients with acute kidney injury (AKI). The pros of early initiation include better control of fluids, electrolytes, and acid-base balance as well as removal of toxins to prevent complications. However, early initiation can also lead to mechanical complications and issues with biocompatibility and anticoagulation. Several studies comparing early vs late RRT are summarized, including the AKIKI trial which found no difference in 60-day mortality and more RRT-free days in the delayed group. The ELAIN study found potential benefits of earlier initiation in rapidly controlling metabolism and fluids to prevent further organ injury. The IDEAL

1. EARLY VS LATE
RRT

2. Early inititaion
 Pros
 Better control of fluid &electrolyte status,
acid-base homeostasis
 Removal of uremic toxins
 Prevention of complications such as
gastric haemorhage & metabolic
encephalopathy
 Cons
 Mechanical complications
 Bio-incompatibility
 Anticoagulant related
 Hypotension, delayed renal recovery
 Drug clearance & overall cost
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ill patients with severe aki. J Crit Care 2009;24:129-40
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indications. Clin J Am Soc Nephrol 2014;9:1577-85

4. AKIKI TRIAL

5. AKIKI Inclusion criteria
 Adults
 ICU with AKI that was compatible with a diagnosis of ATN in the context of ischemic or
toxic injury
 Invasive mechanical ventilation
 Vasopressors
 Or both
 KDIGO stage 3 AKI

6. Categorization
Early group
 AKI stage 3
 Mechanical ventilation or vasopressors
or both
 No potentially life threatening
complication directly related to renal
failure
Delayed group
 Oliguria more than 72 hrs after
randomization
 BUN >112 mg/dl
 Severe hyperkalemia
 Severe metabolic acidosis
 Pulmonary edema

7. Interventions- each study site was free
to decide
 Method of RRT (intermittent or continuous)
 Duration of RRT
 Interval between sessions
 Device settings
 Antoagulation

8. Discontinuation of RRT
 Considered
 Urine output >550/24 hr
 Highly recommended
 Urine output >1000 ml/24 with no diuretics
 Urine output >2000 ml/24 with diuretics
 Mandatory
 Urine output sufficient to decrease in serum creatinine

9. AKIKI trial
311 for early
group
308 delayed group
619 underwent
randomisation
5528 pts eligible
for inclusion

10. KDIGO 3 AKI
Delayed RRT
Conventional
indications
>72 hr after
KDIGO 3 AKI
BUN >112 mg/dl
Early RRT RRT < 12 hr

11. Result
 No difference in 60 day mortality
 More RRT free days in delayed group

13. ELAIN
JAMA 2016

14. Objective
 To determine whether early initiation of RRT in patients who are critically ill patients with
AKI reduces 90 day all cause mortality.

15. Study design
 Single centre RCT
 University Hospital in Germany
 231 critically ill patients with AKI KDIGO 2
 Plasma NGAL level higher than 150 pg/ml
 Duration: Aug 2013- June 2015

16. Interventions
 Early- within 8 hrs of diagnosis of AKI stage 2
 Late- within 12 hrs of diagnosis of AKI stage 3

17. Inclusion in ELAIN
 KDIGO stage 2 AKI
 Plasma NGAL >150 pg/ml
 At least one of the following
 Severe sepsis
 Vasopressors
 Refractory fluid overload
 Non renal organ dysfunction (SOFA >2)
 Age 18-90 years

18. ELAIN trial
KDIGO AKI 2
Early RRT RRT <8hr
Delayed RRT
<12 hr after
AKI 3
Conventional
indications

19. ELAIN patient flow

21. RRT in ELAIN
Identical settings were used in both groups
CVVHDF in all patients
Replacement fluid- Pre filter
Effluent flow- 30 ml/kg/hr
Blood flow >110ml/min
Regional anticoagulation- Citrate

22. ELAIN
Outcome

25. ELAIN Conclusion
 Potential benefits of earlier initiation are attributable to
 More rapid metabolic or uremic control
 More effective prevention and management of fluid overload
 RRT before the onset of severe AKI may attenuate
 Kidney specific and non kidney organ injury
 Due to acidemia, uremia, fluid overload and systemic inflammation
 Limitations
 Single centre RCT
 95% patients recruited were surgical patients (limited generalizability)

27. IDEAL-ICU
NEJM.2018

28. Inclusion criteria
 >18 years of age
 ICU with septic shock
 AKI with failure stage of RIFLE criteria:
 Oliguria (UO <0.3 ml/kg/hr. >24hrs)
 Anuria for >12 hr. or creatinine 3 times the baseline

29. IDEAL ICU TRIAL
AKI- RIFLE,
failure stage
Early RRT RRT <12 hr
Delayed RRT
>48 hr after,
AKI-Failure
stage
Conventional
indications

34. STARRT AKI Trial
• NEJM.2020 (2015-19)
• 168 hospitals in 15 countries
• 11,852 patients met provisional eligibility criteria
• 3019 patients were included

35. Inclusion criteria
 18 Years or older admitted to an ICU
 KDIGO AKI 2 or 3

40. Thank you