Dual Biomarker Strategy with TIMP-2•IGFBP7 and Copeptin Enhances Early Diagnosis and Risk Prediction in HRS-AKI

Background: Acute kidney injury (AKI) in liver cirrhosis, particularly hepatorenal syndrome (HRS), is a life-threatening complication that requires early diagnosis for effective treatment. HRS can potentially be reversed with the early initiation of vasoconstrictors. This study evaluated the diagnostic and prognostic value of cell cycle arrest biomarkers TIMP-2•IGFBP7 and serum copeptin in HRS among Egyptian patients with HCV-related liver cirrhosis. Aims: The primary objectives of this study were to determine whether serum copeptin and urinary TIMP-2•IGFBP7 can distinguish HRS-AKI from HRS-CKD and from non-HRS decompensated cirrhosis, and to evaluate whether these biomarkers, alone and in combination with MELD 3.0, improve short-term mortality risk prediction in patients with HRS-AKI. Methods: This single-center observational study included 80 patients with HCV-related liver cirrhosis (20 compensated, 30 decompensated, 30 HRS) and 20 healthy controls. Urinary TIMP-2•IGFBP7 and serum copeptin levels were measured and analyzed for association with HRS and mortality. Results: Levels of both biomarkers were significantly elevated in HRS patients, particularly in HRS-AKI compared to HRS-CKD ( p < 0.01 ). Serum copeptin showed a strong correlation with TIMP-2•IGFBP7 (r = 0.72, p < 0.01 ). For HRS-AKI diagnosis, TIMP-2•IGFBP7 (cutoff 0.25 ng/mL²/1000) demonstrated 93% sensitivity and 78% specificity, while copeptin (cutoff 9.97 pmol/L) showed 89% sensitivity and 83% specificity. The mortality rate in HRS-AKI was 66.7%, with both biomarkers significantly higher in non-survivors ( p < 0.01 ). TIMP-2•IGFBP7 (cutoff 0.52 ng/mL²/1000) predicted mortality with 92% sensitivity and 84% specificity. Conclusion: In patients with decompensated HCV-related cirrhosis, combined assessment of serum copeptin and urinary TIMP-2•IGFBP7 distinguishes HRS-AKI from HRS-CKD and, when added to MELD 3.0, significantly improves short-term mortality risk stratification beyond conventional clinical scoring alone. Mortality prediction and proposed cutoffs are exploratory and require validation in larger cohorts before routine clinical implementation.