Associations between cardiac and renal biomarkers in patients with type iv cardiorenal syndrome

Background: Type IV cardiorenal syndrome (CRS) results from chronic kidney disease (CKD) causing structural and functional cardiac impairment. Persistent renal dysfunction drives myocardial remodeling, neurohormonal activation, inflammation, endothelial dysfunction, anemia, and mineral metabolism disturbances, increasing cardiovascular risk. While individual cardiac and renal biomarkers predict adverse outcomes, their interrelationships in Type IV CRS are not fully understood. Clarifying these associations may improve understanding of shared mechanisms and enhance risk stratification.

Objective: To evaluate associations between selected cardiac and renal biomarkers in patients with Type IV CRS.

Methods: This study included 39 patients with Type IV CRS and CKD stages II–IV, all exhibiting chronic heart failure (CHF) class III–IV per NYHA classification. The control group comprised 31 age- and sex-matched healthy individuals without structural or functional cardiac or renal abnormalities. The mean age was 52.6 years in patients and 59.0 years in controls; 16 (41.0%) patients were male, 23 (59.0%) female; 15 patients (38.5%) were <60 years, 24 (61.5%) ≥60 years. CHF developed post-myocardial infarction in 32 patients (82.1%), and 7 (17.9%) had a history of stroke. Serum levels of kidney injury molecule-1 (KIM-1), cystatin C, liver-type fatty acid-binding protein (L-FABP), and neutrophil gelatinase-associated lipocalin (NGAL) were measured by ELISA. NT-proBNP and BNP were quantified using electrochemiluminescence immunoassays. Galectin-3, apoptosis-inducing factor (AIF), fibroblast growth factor-23 (FGF-23), endothelin-1, and VEGF-A were assessed by ELISA. Continuous variables were expressed as median and interquartile range (IQR). Intergroup comparisons were performed using the Mann–Whitney U test, and correlations were assessed by Spearman’s rank correlation coefficient (ρ); p<0.05 was considered significant.

Results: Renal biomarkers were significantly elevated versus controls: plasma NGAL Me = 167.2 ng/mL (3.8-fold, p<0.001), plasma KIM-1 Me = 206.8 pg/mL (6.6-fold, p<0.001), urinary KIM-1 Me = 1643.2 pg/mL (3.5-fold, p<0.001), L-FABP Me = 18.1 ng/mL (8.2-fold, p<0.001), cystatin C Me = 4.93 mg/L (6.6-fold, p<0.001). Cardiac biomarkers were also markedly elevated: BNP Me = 1026 pg/mL (20.5-fold, p<0.001), NT-proBNP Me = 1743 pg/mL (26.8-fold, p<0.001), FGF-23 Me = 152.9 pg/mL (3.2-fold, p<0.001), endothelin-1 Me = 19.8 pg/mL (3.4-fold, p<0.001), VEGF-A Me = 117 pg/mL (3.2-fold, p<0.001), AIF Me = 14.6 ng/mL (13-fold, p<0.001), galectin-3 Me = 25.2 ng/mL (3.6-fold, p<0.001).

Spearman correlation analysis revealed strong positive associations between renal and cardiac biomarkers. NGAL, KIM-1, L-FABP, and cystatin C were significantly correlated with BNP, NT-proBNP, endothelin-1, AIF, galectin-3, FGF-23, VEGF-A, and urinary KIM-1 (ρ = 0.432–0.955; p<0.001). Plasma KIM-1 and L-FABP exhibited particularly robust correlations with all cardiac biomarkers (ρ = 0.744–0.951; p<0.001), highlighting the tight interdependence of renal injury and cardiac dysfunction. FGF-23, endothelin-1, and BNP correlations further support their role in the pathophysiology of cardiorenal interaction. These associations emphasize that worsening kidney function directly contributes to cardiac stress, while cardiac dysfunction may reciprocally exacerbate renal injury.

Conclusion: Type IV CRS is characterized by significant dysfunction in both renal and cardiac systems, with strong bidirectional correlations between renal injury and cardiac stress markers. These findings underscore the clinical value of integrated biomarker assessment for monitoring disease severity and guiding management in patients with Type IV CRS.

Dr. Fazil Almammadov is a nephrologist and PhD in Medical Sciences. He graduated from Azerbaijan Medical University and Astrakhan State Medical Academy, where he also completed internship training in surgery. He has undertaken advanced training in chronic kidney disease and dialysis management in Azerbaijan and Moscow. Dr. Almammadov has served in various clinical and administrative positions, including Head of Hemodialysis Department and hospital chief physician. Since 2017, he has been the Director of Narimanov Medical Center. His research focuses on dialysis-related hemodynamic disorders and cardiorenal syndrome. He is the author of more than twenty scientific articles and one methodological manual.