To Recover or Not to Recover: A Urinary Proteomic Perspective on Severe Acute Kidney Injury
Year: 2026
Type: preprint
Study design: Observational Study
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.
Institutions: LAQV Requimte, Associação Científica Proteomass, Laboratório de Análises LAQV-REQUIMTE, Universidade Nova de Lisboa, University of Lisbon, Hospital Prof. Dr. Fernando Fonseca, National Institute of Health Dr. Ricardo Jorge, Servicio Gallego de Salud, University of Pittsburgh Medical Center, Max Planck Institute of Biochemistry, Marche Polytechnic University
Language: English
Topic: Acute Kidney Injury Research
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1240268737, Unidade de Investigação e Desenvolvimento em Engenharia Mecânica e Industrial - UNIDEMI, Laboratório Associado para a Química Verde - Tecnologias e Processos Limpos, Laboratório Associado para a Química Verde - Tecnologias e Processos Limpos, G2756637201, Laboratório Associado para a Química Verde - Tecnologias e Processos Limpos, G2814222956, G3285476938, G3451667969, G3692802076, G3731782831, G4378797157, G4682719911, G4721828077, G4971484151, G5054237811, G5153930962, G5624307780, G5832795443, G5868090805, G6119126181, G6219246445, G6875380692, Laboratório Associado para a Química Verde - Tecnologias e Processos Limpos, G7501588509, G8085826589, G8176001378, G8213652065, G8214220107, G8479097375, G85722789, Laboratório Associado para a Química Verde - Tecnologias e Processos Limpos
OpenAlex ID: W7221779949