Pre-existing iron deficiency anemia and long-term risk of recurrent acute kidney injury in survivors of ICU-associated AKI: a propensity-matched study.

Abstract

Recurrent acute kidney injury (rAKI) is a common complication among critically ill patients and is associated with progressive renal deterioration and increased long-term morbidity. Iron deficiency anemia (IDA) may compromise renal adaptive responses through impaired oxygen delivery and cellular energetics; however, whether pre-existing IDA is associated with rAKI risk remains unclear. We conducted a propensity score-matched retrospective cohort study using the TriNetX database (2010-2024). Adults with AKI during intensive care unit admission were stratified by pre-existing IDA status diagnosed within 6 months before the index AKI episode. A 90-day landmark approach was employed to minimize immortal-time bias. The primary outcome was rAKI occurring between 3 months and 3 years. Secondary outcomes included progression to end-stage renal disease (ESRD), all-cause mortality, major adverse cardiovascular events (MACEs), and estimated glomerular filtration rate (eGFR) decline below 30 ml/min/1.73 m 2 . After matching, 13,002 individuals were included in each cohort. Pre-existing IDA was associated with a significantly higher risk of rAKI (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.44-1.63; p < 0.001) and eGFR decline below 30 ml/min/1.73 m 2 (HR, 1.19; 95% CI, 1.11-1.29; p < 0.001). These associations between IDA and rAKI risk persisted during the extended follow-up (3-5 years) and remained consistent across the sensitivity analyses and demographic subgroups. Although MACEs showed a statistically significant association (HR, 1.16; p < 0.001), the effect size was limited. The associations of IDA with long-term risks of ESRD or mortality were not observed. Pre-existing IDA is associated with an increased risk of rAKI and accelerated renal function decline among critically ill AKI survivors. However, owing to the observational design, a causal relationship cannot be established. Prospective investigations are warranted to validate these observations and to clarify the underlying biological mechanisms.