Fluid balance and acute lung injury in children and young adults receiving continuous renal replacement therapy: a report from the Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK)

The interactions of pulmonary and renal physiology that underlie acute lung injury (ALI) and acute kidney injury (AKI) have been recognized for nearly a century. The understanding of lung-kidney crosstalk has evolved and is recognized as an important factor in patient management and outcomes. We aim to describe the association between fluid accumulation (FA) and ALI with outcomes of critically ill children and young adults requiring continuous renal replacement therapy (CRRT). Planned secondary analysis using data from the Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK). ALI severity was defined using the Berlin oxygenation criteria. Fluid accumulation was categorized as ≤ 10%, > 10-20%, and > 20% at CRRT initiation. Illness severity was quantified using the Pediatric Logistic Organ Dysfunction Score 2 (PELOD-2). The primary outcome was intensive care unit (ICU) mortality. Secondary outcomes included (1) 28-day mechanical ventilation (IMV) free days, (2) 28-day ICU free days, and (3) major adverse kidney events at 90 days (MAKE90) defined by death, persistent kidney dysfunction (eGFR reduction by 25% of baseline), or new dialysis requirement. This is a multinational retrospective cohort study. Invasively ventilated patients aged 0-25 years from January 2015 to December 2021 requiring CRRT for AKI or FA with ALI. There were no interventions. A total of 312 patients were included in the analysis. ALI was mild in 67 (21.5%), moderate in 142 (45.5%), and severe in 103 (33.0%). Fluid accumulation was ≤ 10% in 166 (53.2%), > 10-20% in 60 (19.2%), and > 20% in 86 (27.6%). The ICU mortality was 44.6% (139/312). In the multivariable analysis, neither ALI nor FA category was associated with mortality or MAKE90. Time to CRRT initiation (aOR 1.04, 95% CI 1.01-1.08) and illness severity (aOR 1.25, 95% CI 1.14-1.37) were associated with mortality. CONCLUSIONS:  In children and young adults with ALI receiving CRRT for AKI or FA, longer time to CRRT initiation and illness severity at CRRT initiation were associated with mortality. When accounting for multiple factors, neither ALI nor FA at CRRT initiation were associated with MAKE90 or mortality. Our findings warrant further exploration in a prospective cohort. WHAT IS KNOWN: • Acute kidney injury (AKI) and acute lung injury (ALI) commonly coexist in critically ill children and are associated with increased morbidity and mortality through bidirectional organ crosstalk. • Fluid accumulation (FA) worsens both AKI and ALI, with higher degrees of FA associated with worse outcomes, with continuous renal replacement therapy (CRRT) frequently used to manage the consequences of AKI and FA. WHAT IS NEW: • In this multicenter international cohort of children and young adults with ALI receiving CRRT, longer time to CRRT initiation and illness severity at CRRT initiation, but neither ALI nor FA at CRRT initiation were associated with mortality were associated with mortality. • These findings suggest that FA thresholds at the start of interventions may be less discriminatory in populations with dynamic processes such as severe multiple organ failure.