The Early Bird in Renal Rescue: Timing Matters in Acute Kidney Injury Management-Insights from Target Trial Emulation

Miaowen She¹Yong Liu^2*Jinhu Zhuang³Xi Chen⁴Lili Hu⁴Thuan-Quoc Thach⁵Kin CHEUNG⁶Xiaxia Yu⁷Zheng Xiang^8*

• ¹Hubei University of Medicine, Shiyan, China
• ²Shenzhen Hospital, Southern Medical University, Shenzhen, China
• ³Shenzhen Health Development Research and Data Management Center, Shenzhen, China
• ⁴Shenzhen Hospital of Southern Medical University, Shenzhen, China
• ⁵The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, Hong Kong, SAR China
• ⁶The Hong Kong Polytechnic University, Hong Kong, Hong Kong, SAR China
• ⁷Shenzhen University Medical School, Shenzhen, China
• ⁸Taihe Hospital, Shiyan, China

Background: Acute kidney injury is prevalent in critically ill patients. The optimal timing for initiating renal replacement therapy remains unsettled. Clinical intuition suggests early initiation may be beneficial, but evidence from studies is inconsistent.Methods: A target trial emulation was conducted using the Medical Information Mart for Intensive Care-IV database. Two cohorts were analyzed: broader cohort (stage ≥1, N=7607) and the severe cohort (stage 3, N=943). Cox proportional hazards models with inverse probability weighting were used to estimate the causal effect on 90-day and 30-day mortality, with sensitivity analyses using accelerated failure time models and augmented inverse probability weighting.Results: In the broader cohort, early initiation was associated with lower 90-day (HR 0.653, 95% CI 0.512-0.834) and 30-day mortality (HR 0.649, 95% CI 0.504-0.835).However, accelerated failure time models indicated no survival benefit and potentially worse outcomes, with a 14.8% reduction in 90-day survival and a 14.1% reduction in 30-day survival. Augmented inverse probability weighting analysis further confirmed these findings, showing a risk difference of 2.6 percentage points between early and late initiation of RRT. In severe cohort, early initiation was associated with lower 90day mortality (HR 0.561, 95% CI 0.341-0.921) and 30-day mortality (HR 0.604, 95% CI 0.357-1.022), with accelerated failure time models confirming longer survival.Augmented inverse probability weighting analysis in this group showed a risk difference of 1.7 percentage points.Early initiation appears beneficial in severe cohort (stage 3), but not in broader cohort (stage ≥1), where it may even be harmful. This highlights the need for personalized treatment based on acute kidney injury severity and further research to optimize renal replacement therapy timing.