To Recover or Not to Recover: A Urinary Proteomic Perspective on Severe Acute Kidney Injury

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Abstract

Rationale & Objective

Early prediction of renal non-recovery after acute kidney injury (AKI) could support risk-adapted follow-up and clinical decision-making. We evaluated whether a urinary fatty acid-binding protein 3 (FABP3)/apolipoprotein A-I (APOA1) ratio based on Total Protein Approach (TPA) quantification could discriminate renal recovery from non-recovery after severe AKI.

Study Design

Exploratory biomarker discovery study with outcome-blinded independent validation.

Setting & Participants

Critically ill adults with KDIGO stage 2 or 3 AKI. Urine was collected 48 hours after AKI diagnosis. The discovery cohort included 20 patients (10 recovered and 10 non-recovered), and the outcome-blinded validation cohort included 10 patients.

New Predictor

Urinary TPA-derived FABP3/APOA1 ratio (AKI TPA index ).

Outcome

Renal recovery at day 14, defined as survival with serum creatinine returning to within 0.3 mg/dL or 150% of baseline; patients not meeting these criteria were classified as having non-recovery.

Analytical Approach

Urinary proteins were analyzed by LC-MS/MS and quantified using TPA. Differential analysis identified FABP3 and APOA1 as oppositely associated with renal outcome. A predefined FABP3/APOA1 threshold of 1 classified patients as non-recovery-like (>1) or recovery-like (<1) and was subsequently applied to the outcome-blinded validation cohort.

Results

In the discovery cohort, the AKI TPA index correctly classified 17 of 20 patients (accuracy, 85.0%; sensitivity, 80.0%; specificity, 90.0%; ROC AUC, 0.930). In the validation cohort, 9 patients were evaluable, of whom 7 were correctly classified (accuracy, 77.8%; sensitivity, 75.0%; specificity, 80.0%; ROC AUC, 0.950).

Limitations

The exploratory design and limited cohort size warrant further validation in larger, independent populations.

Conclusions

The urinary FABP3/APOA1 TPA ratio showed encouraging preliminary discrimination of renal recovery after severe AKI and warrants prospective clinical validation in larger, independent multicenter cohorts.

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