Timing of recurrent acute kidney injury is associated with mortality and chronic kidney disease progression in very elderly patients

Abstract Acute kidney injury (AKI) recurrence is common in elderly patients, but whether the timing of recurrence influences clinical outcomes remains unknown. We hypothesized that early and late recurrence represent two distinct phenotypes with opposing outcomes—early recurrence being associated with short-term mortality, and late recurrence being associated with chronic kidney disease (CKD) progression. This multicenter retrospective cohort study included patients aged ≥ 75 years who recovered from an index AKI episode between January 2017 and December 2024. Recurrent AKI was defined as a new serum creatinine rise (≥ 26.5 µmol/L within 48 h or ≥ 50% within 7 days) after complete recovery from the preceding episode. Recurrence timing was categorized into four intervals: 8–14 days, 15–21 days, 22–28 days, and more than 28 days. Among 2,382 patients, 51.7% (1232/2382) experienced a second AKI episode. Recurrence occurred within 8–14 days in 10.4% (248/2382) of patients, within 15–21 days in 13.3% (316/2382), within 22–28 days in 13.8% (328/2382), and after 28 days in 13.2% (340/2382). Early recurrence (8–21 days) was characterized by acute severity markers (sepsis, mechanical ventilation, advanced AKI stage), whereas late recurrence (> 21 days) was characterized by chronic vulnerability markers (lower baseline eGFR, nephrotoxicity). New-onset CKD occurred in 17.1% (24/140) of those with early recurrence (8–14 days), rising to 36.3% (114/314) in those with late recurrence (> 28 days) ( P < 0.001). Compared with a single AKI episode, recurrence at any time window was independently associated with higher 90-day and 1-year mortality. The adjusted HRs for 90-day mortality were 7.826 (95% CI: 4.051–13.106) for 8–14 days, 5.965 (95% CI: 3.087–11.526) for 15–21 days, 4.484 (95% CI: 2.276–8.835) for 22–28 days, and 2.506 (95% CI: 1.206–5.204) for > 28 days; for 1-year mortality, the HRs were 2.713 (95% CI: 1.942–3.786), 2.654 (95% CI: 1.917–3.687), 1.965 (95% CI: 1.396–2.765), and 1.583 (95% CI: 1.108–2.264), respectively (all P < 0.01). AKI recurrence at any time window independently increases mortality. However, early recurrence (≤ 21 days) is independently associated with higher mortality, whereas late recurrence (> 21 days) is associated with higher CKD progression in descriptive analyses. Recurrence timing, not just frequency, may help guide post-discharge risk stratification and follow-up planning.