1.
Earlier vs Later Renal Replacement
Therapy (RRT)
Johan Mårtensson

2.
Conflict of interest: None

3.
Time for RRT? –Yes!
Mr. Jones, 58 yr
Day 4 in ICU
Severe sepsis
Fluid balance ++++
FiO2 0.7
S-creatinine 540 µmol/L
Urea 40 mmol/L
S-K+ 6.2 mmol/L
Urine output 20 mL/hour
(lasix infusion 40 mg/hr)

4.
”Late” RRT
”Conventional” or ”absolute” indications for RRT in AKI:
• Refractory hyperkalemia (e.g. K+ >6)
• Refractory acidemia & metabolic acidosis (e.g. pH <7.2)
• Refractory pulmonary edema due to fluid overload
• Uremic complications (e.g. bleeding, pericarditis)
• Overdose/toxicity from a dialyzable drug/toxin

5.
Contemporary AKI staging
KDIGO
stage
Plasma creatinine Urine output
1 1.5-2 times baseline
OR
>26.5 µmol/l increase
<0.5 ml/kg/h for 6-12 h
2 2.0-2.9 times baseline <0.5 ml/kg/h for ≥12 h
3 3.0 times baseline
OR
Increase to ≥354 µmol/l
<0.3 ml/kg/h for ≥24 h
OR
Anuria for ≥12 h
the Kidney Disease Improving Global
Outcomes (KDIGO) guidelines

6.
The AKIKI trial

7.
AKIKI setup
620 pts, 31 ICUs
• KDIGO stage 3 AKI
• Mechanical ventilation and/or catecholamine infusion
• No absolute indication
Early Group (n=311)
Start RRT immediately
Late Group (n=308)
Start RRT if:
Absolute indication OR
Oliguria >72 hrs

8.
AKIKI treatmentRandomisation
2 hours
57 h
0
20
40
60
80
100%receivingRRT
Early Late
49% no RRT
51% RRT
≥1 absolute indication
(82%)
Oliguria >72 h (18%)

9.
AKIKI 60-day mortality
P=0.79
0
20
40
6060-daymortality,%
Early Late

10.
AKIKI secondary outcomes
P=0.12
0
2
4
6
8
10
DependenceonRRTday60,%
Early Late
P=0.03
0
5
10
15
20
Catheter-relatedbloodstreaminfection,%
Early Late

11.
The ELAIN trial

12.
ELAIN setup
231 pts (mainly post-surgical), single-center
• KDIGO stage 2 AKI
• Plasma Neutrophil gelatinase-associated lipocalin (NGAL) >150 ng/ml
• Any of the following:
• Severe sepsis
• Vasoactive support
• Fluid overload
• Worsening SOFA score
Early Group (n=112)
RRT within 8 h from KDIGO 2
Late Group (n=119)
RRT within 12 h from KDIGO 3 OR
Absolute indication

13.
ELAIN treatment
Randomisation 6 hours
26 hours
0
20
40
60
80
100
%receivingRRT
Early Late
9% no RRT
91% RRT
-KDIGO 3 (84%)
-Absolute
indication (16%)

14.
ELAIN 90-day mortality
P=0.03
0
20
40
60
90-daymortality,%
Early Late

15.
ELAIN renal recovery
P=0.62
0
20
40
60
80
100
meanofrecovery90surv
Early Late
Survivors
P=0.02
0
20
40
60
80
100
Renalrecoveryday90,%
Early Late
All patients

16.
Other factors affecting decision
making
• Anticipation of worsening kidney function
• Worsening nonrenal organ dysfunction
• Expected high solute burden (e.g. tumor lysis
syndrome)
• Facilitate other supportive measures (nutrition,
drugs, other fluids)
• Perception of benefit

17.
*
* Treating clinician must confirm clinical equipoise

18.
Take-home message
• No strong evidence that ”early” RRT will
improve outcomes
• ”Early” RRT may expose some patients to
unnecessary treatment
• Timing based on patient characteristics, illness
severity and trends in
physiology/biochemistry