The Landscape of Biomarkers in
ICU
‐Associated
AKI
: From Protein Markers to Cell‐Free Nucleic Acids
Qi Zhu, Feng Yang, Hua Zheng, Xinxin Guo, Zhijin Chen, Limin Chen, Daoli Wang, Jiaqi Wang, Xinmeng Wang, Zhiyuan Huang, Zhenhua Ji ABSTRACT
Background
Acute kidney injury (AKI) affects approximately 30%–60% of intensive care unit (ICU) admissions, but early detection remains difficult because creatinine‐ and urine‐output‐based KDIGO criteria are delayed and confounded in critical illness.
Objective
To summarize the biomarker landscape for ICU‐associated AKI, focusing on kidney‐targeted injury/stress proteins and circulating cell‐free DNA (cfDNA), including mitochondrial DNA (mtDNA).
Methods
PubMed/MEDLINE and Embase were searched from inception to December 31, 2025, using terms related to AKI, critical illness, NGAL, KIM‐1, IL‐18, L‐FABP, [TIMP‐2]·[IGFBP7], cfDNA, mtDNA, and damage‐associated molecular patterns. Adult ICU studies reporting diagnostic performance, risk stratification, or clinically relevant outcomes were prioritized, especially in sepsis, cardiac surgery, shock, and trauma.
Results
NGAL, KIM‐1, IL‐18, L‐FABP, and [TIMP‐2]·[IGFBP7] often rise before creatinine or urine‐output changes, providing early kidney‐proximal signals of tubular injury or stress. cfDNA/mtDNA instead reflects systemic cell death, mitochondrial damage, and innate immune activation, capturing multi‐organ injury and adding prognostic information beyond clinical scores and creatinine. Across ICU phenotypes, combining clinical risk, an early kidney‐targeted marker, and cfDNA/mtDNA may improve identification of patients at risk for severe AKI, renal replacement therapy, and death.
Conclusions
Multimarker strategies may widen the diagnostic window and sharpen prognostication in ICU‐associated AKI. Routine implementation will require standardized pre‐analytical handling, assay harmonization, biomarker‐guided pragmatic trials, and trajectory‐based decision tools that demonstrate clinical benefit.