In patients with septic shock and associated severe acute kidney injury without immediate need for dialysis, does an early start renal replacement therapy (RRT) strategy portend benefits over a delayed start strategy?
There is no clinically significant difference between an early start RRT strategy and a delayed start RRT strategy.
Sepsis remains one of the most frequent reasons for ICU admission throughout the world. The development of AKI in the context of septic shock is well documented with rates ranging between 40-75% . A common dilemma within the ICU in these patients is whether to begin RRT early upon development of severe acute kidney injury or wait until an acute indication for dialysis arises in these patients. The AKIKI study in 2016 concluded there was no significant difference in the outcomes of patients who developed severe AKI from any etiology and received early initiation of RRT compared to those who received delayed RRT . Within this trial, septic shock represented about 67% of the patient population with no appreciable difference in the primary outcome seen for this subgroup. These results were contrasted by the single-center ELAIN trial in Germany which found a dramatic mortality benefit in general ICU patients with severe AKI . While there is ongoing debate between these two trials and their methodological differences, a focused trial towards severe AKI in sepsis has not been performed.
The IDEAL-ICU was a multicenter, randomized, open-label trial designed to see if there was any difference between early initiation of RRT and delayed initiation of RRT specifically in patients with septic shock. The trial was expected to enroll 864 patients however was stopped early after the second pre-planned interim analysis for futility after randomization of 488 patients. There was no difference in the 90-day mortality rate among both groups and no difference seen in any major secondary outcome as well.
The growing body of evidence, including the IDEAL-ICU trial, suggests there is no benefit to an early initiation RRT strategy compared to waiting for either acute indication for dialysis to arise or waiting an extra couple of days. There has yet to be a convincing argument made to show consistent decreased rates of mortality or ICU utilization with an early initiation strategy. Given the lack of difference in mortality or any major outcomes, there is likely a higher resource and financial burden associated with early initiation of RRT without any direct benefit to the patient.
As of December 2018, no guidelines have been published that reflect the results of this trial.
- Multicenter, randomized, open-label trial
- Early initiation of dialysis (n=239)
- Delayed initiation of dialysis (n=238)
- Setting: 29 intensive care units in France
- Enrollment: 2012-2016
- Follow-up period: 90 days
- Analysis: Intention-to-treat
- Primary outcome: Death from any cause at 90 days after randomization
- Age > 18 years
- Admitted to ICU within 48 hours of development of septic shock (i.e. vasopressors)
- Acute kidney injury meeting one of RIFLE criteria including oliguria, anuria for 12+ hours, or serum creatinine of 3 times their baseline or >350umol/L with an associated acute rise of >44umol/L
- End-stage renal disease already on RRT
- Obstructive AKI
- Acute indication for urgent RRT before randomization (K > 6.5mmol/L, pH <7.15, or refractory volume overload)
- Previously received RRT in the ICU
- Moribund state
- Pre-existent comorbid condition with expected survival <28 days (End-stage cardiac disease, pulmonary disease, liver disease, poorly controlled cancer, or post-anoxic encephalopathy)
- DNR order in chart
From the early initiation group.
- Mean age: 69 years
- Male sex: 58%
- BMI: 28.8
- Chronic kidney disease: 13%
- SOFA score at enrollment: 12.2
- Mechanically ventilated: 89%
- Randomization to a group:
- Early initiation of RRT - Initiation of RRT within 12 hours after documentation of severe AKI (At least one of oliguria >24 hours, anuria >12 hours, serum creatinine >3x baseline, or creatinine >350umol/L with a rapid rise of >44umol/L)
- Delayed initiation of RRT - Monitored until they meet criteria for acute indication of dialysis (K > 6.5mmol/L, pH < 7.15, or refractory fluid overload with pulmonary edema). If no acute indication for dialysis, then initiation of RRT is implemented at 48 hours unless renal recovery is made (decline in creatinine and urine output >1000ml/24 hours)
Comparisons are early initiation group vs. delayed initiation group.
- 90-day mortality
- 58% vs. 54% (p=0.38)
- 28-day mortality
- 45% vs. 42% (p=0.48)
- Median time of initiation of RRT after diagnosed with failure-stage AKI
- 7.6 hours vs. 51.5 hours (p<0.001)
- Patients who received RRT
- 97% vs. 62% (p<0.001)
- Median days free of RRT
- 12 vs. 16 (p=0.006)
- Median days free of mechanical ventilation
- 2 vs. 3 (p=0.19)
- Median length of ICU stay
- 11 days vs. 10 days (p=0.91)
- Cumulative fluid balance at day 7
- 5570ml vs. 5878ml (p=0.75)
- Development of hyperkalemia
- 0% vs. 4% (p=0.03)
- Inconsistency between using KDIGO or RIFLE criteria for inclusion criteria exists between AKI studies in ICU populations
French Ministry of Health
- Alobaidi R et al. Sepsis-associated acute kidney injury. Semin. Nephrol. 2015. 35:2-11.
- Gaudry S et al. Initiation Strategies for Renal-Replacement Therapy in the Intensive Care Unit. N. Engl. J. Med. 2016. 375:122-33.
- Zarbock A et al. Effect of Early vs Delayed Initiation of Renal Replacement Therapy on Mortality in Critically Ill Patients With Acute Kidney Injury: The ELAIN Randomized Clinical Trial. JAMA 2016. 315:2190-9.