Clinical Significance of Kallikrein As A Diagnostic and Prognostic Biomarker in Cardiorenal Syndrome Associated with Chronic Heart Failure

Abstract

Background. Chronic heart failure (CHF) remains one of the leading challenges in modern healthcare systems worldwide and is frequently accompanied by impaired renal function. The progressive and interrelated deterioration of cardiac and renal function leads to the development of cardiorenal syndrome (CRS), which significantly worsens patient prognosis. In recent years, alongside neurohumoral mechanisms, the kallikrein–kinin system has been increasingly recognized as an important contributor to CRS pathogenesis; however, its diagnostic value has not yet been sufficiently elucidated. Objective. To evaluate the diagnostic and potential prognostic significance of kallikrein levels in the early stages of cardiorenal syndrome developing in patients with chronic heart failure, and to determine their relationship with NT proBNP, aldosterone, and renal function parameters. Methods. This prospective observational study included 115 patients with chronic heart failure classified as New York Heart Association (NYHA) functional classes II–III. Patients were divided into two groups according to functional class. Serum levels of kallikrein, NT-proBNP, aldosterone, cystatin C, and creatinine were measured. Glomerular filtration rate (GFR) was calculated using the CKD-EPI equation. Statistical analysis was performed using Student’s t-test and Pearson correlation analysis. Results. Kallikrein levels were significantly lower in patients with NYHA class III compared to class II (535.86±12.37 vs. 778.79±17.8 ng/mL; p<0.001). In contrast, NT proBNP levels were significantly higher (738.6±45.8 vs. 587.3±59.9 pg/mL; p<0.05). Kallikrein demonstrated a negative correlation with NT-proBNP (r = -0.51; p<0.001) and aldosterone (r = -0.48; p<0.001), while showing a positive correlation with GFR calculated based on cystatin C (r = 0.66; p<0.001). Conclusion. Decreased kallikrein levels are associated with increased severity of cardiorenal syndrome and exhibit inverse relationships with NT-proBNP and aldosterone, while correlating positively with renal function parameters. The combined assessment of these biomarkers may have potential clinical value for the early diagnosis and prognostic stratification of cardiorenal syndrome.