Key Trials Comparing Early versus Delayed RRT Initiation in AKI
Major Randomized Controlled Trials
The two pivotal RCTs published in 2016 showed contradictory results regarding early versus delayed RRT initiation, with one demonstrating benefit and the other suggesting potential harm. 1
ELAIN Trial (2016)
- Single-center German RCT of 231 critically ill patients with KDIGO stage 2 AKI and elevated NGAL (>150 ng/mL) 2
- Early group: RRT initiated within 8 hours of KDIGO stage 2 diagnosis (median 6 hours) 2
- Delayed group: RRT initiated within 12 hours of KDIGO stage 3 or not at all (median 25.5 hours) 2
- Primary outcome: 90-day mortality was significantly lower in early group (39.3% vs 54.7%; HR 0.66, P=0.03) 2
- Secondary outcomes favored early initiation: better renal recovery (53.6% vs 38.7%, P=0.02), shorter RRT duration (9 vs 25 days, P=0.04), and shorter hospital stay (51 vs 82 days, P<0.001) 2
- One-year follow-up data showed sustained benefit with early initiation: composite outcome of major adverse kidney events occurred in 64.9% vs 89.1% (OR 0.23, P<0.001) 3
Unnamed Second 2016 RCT
- This trial suggested potential harm with early RRT, including increased mortality, dialysis dependence, and central line infections 1
- Enrollment criteria and timing definitions differed from ELAIN 1
- The Surviving Sepsis Campaign guidelines judged this evidence as low certainty due to indirectness (many non-septic patients) and imprecision 1
Comprehensive Meta-Analyses
2021 Systematic Review with Trial Sequential Analysis
- Included 11 RCTs with 5,086 patients; found no mortality benefit with early RRT initiation 4
- Pooled 28-day mortality: RR 1.01 (95% CI 0.94-1.09, P=0.77, I²=0%) 4
- Trial sequential analysis crossed the futility boundary, indicating sufficient evidence to conclude no benefit 4
- Early RRT associated with higher incidence of hypotension (RR 1.42, P<0.00001) and RRT-associated infections (RR 1.34, P=0.04) 4
- Median time to RRT ranged from 2-7.6 hours (early) versus 21-57 hours (delayed) across studies 4
2023 Updated Meta-Analysis
- Analyzed 15 RCTs with 5,625 patients; confirmed no survival benefit at any time point 5
- 28/30-day mortality: RR 1.01 (95% CI 0.94-1.08, P=0.87) 5
- 60-day mortality: RR 0.87 (95% CI 0.71-1.06, P=0.16) 5
- 90-day mortality: RR 1.00 (95% CI 0.88-1.13, P=0.97) 5
- Early RRT associated with more adverse events without improving ventilator-free days, vasoactive agent-free days, or RRT-free days 5
Special Population Studies
Small 2002 Trial in Sepsis
- Evaluated early versus delayed RRT in sepsis; included only 4 septic patients and showed no benefit 1
2025 Burn Patient Cohort Study
- Retrospective study of 79 burn patients (mean 68.82% TBSA) comparing early (KDIGO stage 1-2) versus delayed (KDIGO stage 3) RRT 6
- In-hospital mortality trended higher in early group (42.86% vs 29.73%, P=0.227) 6
- Delayed group had significantly higher rate of partial renal function recovery at 48 hours (78.26% vs 36.84%, P=0.003) 6
- Subgroup analysis: patients with stage 3 AKI receiving RRT beyond 24 hours had highest survival rate 6
Guideline Interpretation of Trial Evidence
The Surviving Sepsis Campaign 2016 guidelines concluded that the possibility of harm (central line infections, increased dialysis dependence) outweighs potential benefits, recommending against early RRT in sepsis patients with AKI based solely on creatinine elevation or oliguria without definitive indications 1