Kallikrein Activation and Its Association with NT-proBNP, Cystatin C–Derived eGFR, and Cardiac Remodeling in Patients with Chronic Heart Failure and Early Cardiorenal Syndrome

Abstract

Background: Neurohormonal activation plays a central role in the progression of chronic heart failure (CHF) and in the development of cardiorenal syndrome (CRS). However, the role of the kallikrein–kinin system in early CRS remains insufficiently investigated.

Objective: To evaluate the association between serum kallikrein concentrations and NT-proBNP, cystatin C–derived estimated glomerular filtration rate (eGFR), and cardiac remodeling parameters in patients with New York Heart Association (NYHA) class III CHF and early CRS, and to assess the effect of guideline-directed medical therapy.

Methods: This study included 85 patients with NYHA class III CHF (mean age 66.7 ± 1.0 years) and 40 healthy controls. Patients were stratified according to left ventricular ejection fraction (LVEF ≥40% and <40%). Serum kallikrein, NT-proBNP, aldosterone, and cystatin C concentrations were measured, and eGFR was calculated using the CKD-EPI cystatin C equation. Correlations were evaluated, and biomarker dynamics were reassessed after six months of four-component guideline-directed medical therapy.

Results: Patients with LVEF <40% had significantly lower kallikrein concentrations (448.6 ± 9.6 vs. 581.0 ± 10.7 ng/mL; P < 0.001), higher NT-proBNP concentrations (1123.3 ± 77.7 vs. 547.8 ± 46.5 pg/mL; P < 0.001), and lower eGFR (47.3 ± 0.8 vs. 56.2 ± 1.1 mL/min/1.73 m²; P < 0.001) than patients with LVEF ≥40%. Kallikrein correlated positively with eGFR (r = 0.55; P < 0.001) and inversely with NT-proBNP (r = −0.51; P < 0.001). After six months of therapy, kallikrein concentrations increased significantly and cardiac and renal parameters improved, with a more pronounced effect in patients receiving eplerenone.

Conclusion: Serum kallikrein is associated with both cardiac and renal function in early cardiorenal syndrome and may serve as a candidate biomarker of neurohormonal adaptation and therapeutic response in patients with chronic heart failure.

Keywords:

chronic heart failure, cardiorenal syndrome, kallikrein, NT-probnp, cystatin C, estimated glomerular filtration rate, cardiac remodeling, mineralocorticoid receptor antagonists

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