Highlight
– Survivors of in-hospital acute kidney injury (AKI) have an increased long-term risk of death (RR 1.42), dialysis (RR 2.48), and chronic kidney disease (CKD; RR 1.71) compared with matched hospitalized controls.
– Meta-analysis of 14 matched-control studies including 1,058,109 patients, median follow-up ~3 years.
– Findings support systematic post-discharge kidney monitoring and risk-reduction strategies after AKI.
Background
Acute kidney injury (AKI) is common among hospitalized patients, particularly in critical care settings. Short-term outcomes and in-hospital mortality associated with AKI are well documented; however, the magnitude and clinical relevance of longer-term outcomes among hospital survivors have been debated. These longer-term outcomes include all-cause mortality after discharge, progression to chronic kidney disease (CKD), and development of end-stage kidney disease (ESKD) requiring long-term dialysis. Establishing the relationship between an episode of AKI and these downstream risks is crucial for post-discharge planning, allocation of nephrology resources, and the design of interventions to mitigate long-term harm.
Study design
This work synthesized evidence from a systematic review and meta-analysis by Fresilli and colleagues (2025) of original, peer-reviewed studies that compared long-term outcomes in hospitalized patients who experienced an AKI episode and survived to discharge versus matched hospitalized controls without AKI. Key inclusion criteria were: a clearly defined AKI episode during hospitalization, survival to hospital discharge, presence of a control group without AKI, and reporting of at least one long-term outcome (mortality, dialysis, or CKD) with minimum follow-up of 1 year. Two independent reviewers extracted study characteristics, populations, follow-up duration, and outcome data; discrepancies were resolved by consensus. Fourteen studies met inclusion criteria, together including 1,058,109 matched patients with a median follow-up of approximately 3 years.
Key findings
This section summarizes the primary pooled results and their clinical interpretation. All numerical results are taken from the pooled analyses reported by Fresilli et al.
Long-term mortality
Across included studies, 137,506 of 519,672 patients who experienced AKI and survived to discharge died during the longest follow-up reported by each study (26.4%), compared with 93,702 of 530,663 matched controls without AKI (17.6%). The pooled relative risk (RR) of death for AKI survivors versus controls was 1.42 (95% CI, 1.13–1.78; p = 0.002). This indicates a 42% higher relative risk of all-cause mortality over extended follow-up after surviving an in-hospital episode of AKI.
Need for dialysis (progression to ESKD)
Among studies that reported incident long-term dialysis, 1,928 of 42,529 AKI survivors (4.5%) subsequently received dialysis compared with 854 of 42,529 matched controls (2.0%). The pooled RR was 2.48 (95% CI, 1.79–3.43; p < 0.001), signifying that AKI survivors had more than double the risk of progressing to dialysis-dependent kidney failure compared with similar patients who did not experience AKI in hospital.
Chronic kidney disease (CKD)
Among patients with available data to assess CKD incidence or progression, 2,956 of 5,739 AKI survivors (51.5%) developed CKD versus 2,902 of 7,781 controls (37.3%). The pooled RR for CKD after AKI was 1.71 (95% CI, 1.33–2.19; p < 0.001). This indicates a substantially higher risk of subsequent CKD in patients who had AKI during hospitalization.
Interpretation of effect sizes and absolute risks
The relative risks are clinically meaningful and translate into considerable absolute increases in adverse outcomes at the population level, particularly for mortality and the need for dialysis. For example, a control-group mortality of 17.6% rising to 26.4% among AKI survivors represents an absolute excess mortality of approximately 8.8 percentage points over the median follow-up. Similarly, dialysis incidence increased from about 2.0% to 4.5%, an absolute change of 2.5 percentage points. These are substantial differences when applied to large populations of hospitalized patients.
Heterogeneity and study characteristics
The included studies varied in patient case-mix (surgical, medical, critically ill), AKI definitions and severity classifications, baseline prevalence of CKD, and length of follow-up (median 3 years). Although all studies used matched controls, methods and variables used for matching differed across reports. The pooled estimates therefore reflect an average effect across heterogeneous practice settings and populations, and heterogeneity was apparent in some analyses.
Expert commentary
These results add robust, contemporary evidence supporting a direct and clinically significant association between an episode of in-hospital AKI and adverse long-term kidney and survival outcomes. The study design focus on matched-control studies strengthens causal inference compared with uncontrolled cohorts, because matching reduces confounding by measured baseline factors. However, several limitations warrant careful interpretation.
Limitations and potential biases
First, matched-control observational studies cannot eliminate residual confounding by unmeasured variables (for example, frailty, socio-economic status, or severity of acute illness elements not captured in matching). Second, AKI severity and recovery patterns vary; many included studies aggregated AKI stages, yet the long-term risks likely differ by AKI stage, duration, and completeness of renal recovery. Third, baseline kidney function ascertainment and the definition of incident CKD were heterogeneous; misclassification is possible. Fourth, follow-up completeness, competing risks (notably death precluding CKD diagnosis), and differing thresholds for dialysis initiation between centers could affect estimates. Finally, the median follow-up of ~3 years may miss very late outcomes and does not capture lifetime risk.
Biological plausibility
Several mechanistic pathways plausibly link AKI to later CKD and increased mortality. AKI can trigger maladaptive repair in the kidney, including persistent inflammation, fibrosis, microvascular rarefaction, and loss of nephron mass — processes that accelerate CKD progression. AKI may also unmask pre-existing subclinical kidney disease or worsen comorbid conditions (cardiovascular disease, infections) that raise long-term mortality risk. These biologic insights support the observed epidemiologic associations.
Clinical implications
From a practical standpoint, these findings reinforce the need for systematic post-discharge strategies after AKI. Key elements include early outpatient reassessment of kidney function (including creatinine and urine albumin), medication review to optimize renoprotective therapies and avoid nephrotoxins, blood pressure control, consideration of timely nephrology referral for patients at high risk of CKD progression (for example, persistent creatinine elevation, proteinuria, or advanced age/comorbidities), and patient education on AKI as a sentinel event. The findings also support integration of AKI history into chronic disease management plans and quality metrics.
Unanswered questions and research priorities
Despite clear associations, important gaps remain. Which interventions after hospital discharge reduce long-term mortality and CKD progression after AKI? What are the optimal timing and intensity of follow-up, and which patients most benefit from nephrology-led care? Can biomarkers or imaging better risk-stratify AKI survivors? Randomized trials assessing structured post-AKI clinics, targeted renoprotective regimens, and early rehabilitation would be valuable. Standardization of AKI definitions, staging, and CKD outcome reporting in future studies would improve comparability.
Conclusion
The meta-analysis by Fresilli et al. synthesizes matched-control observational data showing that survivors of in-hospital AKI face significantly higher long-term risks of death, dialysis, and CKD compared with hospitalized patients without AKI. The magnitude of these associations is both statistically significant and clinically important. Clinicians should treat an episode of AKI as a sentinel event that prompts structured post-discharge evaluation and risk-reduction strategies. Health systems should consider pathways to ensure appropriate follow-up, and researchers should prioritize trials to identify effective interventions to reduce long-term harms after AKI.
Funding and clinicaltrials.gov
The summary information provided here is based on Fresilli et al. (2025). Funding sources and trial registrations for the individual studies included in the systematic review are reported in the original publication; readers should consult the full paper for those details. The systematic review itself is not a clinical trial and therefore has no ClinicalTrials.gov registration.
References
1. Fresilli S, Labanca R, Losiggio R, Asiller ÖÖ, Baiardo Redaelli M, Yavorovskiy AG, Vives M, Beretta L, Bellomo R, Landoni G; Acute Kidney Injury (AKI) Study Group Collaborators. Long-Term Outcomes After Acute Kidney Injury During Hospitalization: A Systematic Review and Meta-Analysis of Matched Controls Studies. Crit Care Med. 2025 Nov 17. doi: 10.1097/CCM.0000000000006953 . Epub ahead of print. PMID: 41247233 .
2. KDIGO Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int Suppl. 2012;2:1–138.
