Urinary Tissue Inhibitor of Metalloproteinases-2 and Insulin Like Growth Factor Binding Protein-7 as Early Markers of Cardiorenal Syndrome Type -1 in Patients Hospitalized with Acute Heart Failure

Open Access

Abstract

Background: Type 1 Cardiorenal Syndrome (CRS) is defined as an acute worsening of cardiac function-whether in the context of acute decompensated heart failure or acute de novo heart failure-that leads to acute kidney injury (AKI). Acute kidney injury (AKI) during hospitalization is associated with poor prognosis. Urinary [TIMP-2] × [IGFBP-7] has been investigated as early marker which helps to detect early deterioration of the renal function and in turn help to initiate necessary interventions or withhold deleterious medication or interventions which could aggravate acute kidney injury. Aim of the study: The main aim of this study was to demonstrate the usefulness of Urinary [TIMP-2] × [IGFBP7] as early detector of cardiorenal syndrome type 1 in patients with acute heart failure with normal renal function assessed by serum creatinine level on the day of admission (day 1). Methods & Materials: This was a prospective observational study which was conducted in the Department of Nephrology, BMU, Dhaka, Bangladesh. The study period ranged from June 2023 to March 2025.First we collected blood for s. creatinine in patients with acute heart failure (acute decompensated heart failure or acute de novo heart failure) on admission day (day 1). Those who had normal renal function (s. creatinine <1.3 mg/dl) were included in the study and urine sample of the patients was collected on day 1 for urinary TIMP-2, IGFBP-7. Then serum creatinine was subsequently followed up on day 3 (48 hours after admission) and day 7 to identify the development of CRS type 1. Patients were classified into AKI and non-AKI groups, and Urinary [TIMP-2] × [IGFBP7] were compared between these groups. Statistical analysis was performed using SPSS-23. Result: Among 58 participants, 39.7% (N=23) developed AKI, while 60.3% (n=35) remained Non-AKI. The mean age of AKI patients was higher (67.91±8.66 years) than non-AKI (55.85±10.79 years), but the difference was not statistically significant (p=0.381). Diabetes mellitus was significantly more prevalent in the AKI group (60.9% vs. 31.4%, p=0.027). Urinary [TIMP-2] × [IGFBP-7] levels were significantly higher in AKI patients (1.01±0.56 ng/ml) compared to Non-AKI (0.24±0.11 ng/ml, p<0.001). The ROC analysis showed an AUC of 0.915 (95% CI: 0.842-0.988, p<0.001), indicating strong diagnostic accuracy of urinary [TIMP-2] × [IGFBP-7] for predicting AKI in acute heart failure patients. The optimal cut-off value 0.312 (ng/m1)2/1000 yielded a sensitivity of 87.0%, specificity of 74.3%, and an overall accuracy of 80.7%. Conclusion: These findings suggest that urinary [TIMP-2] × [IGFBP-7] is a promising early biomarker for detecting AKI in acute heart failure patients, with good discriminative ability and potential clinical utility in predicting CRS Type 1.