From heart to kidney: FGF23, SuPAR, and NAG as early biomarkers of cardiorenal syndrome in acute heart failure

Abstract Background Acute heart failure (AHF) often occurs concurrently with renal impairment, forming the clinical entity known as cardiorenal syndrome. Conventional biomarkers frequently do not identify early renal impairment in patients with AHF. Objectives The present study aimed to assess the clinical applicability of fibroblast growth factor-23 (FGF23), soluble urokinase plasminogen activator receptor (SuPAR), and N-acetyl-β-D-glucosaminidase (NAG) as potential biomarkers for the discrimination of kidney disease in the setting of AHF. Patients and methods This prospective observational pilot study was performed from 2024 to 2025 in the critical care units of Mansoura University. In total, 80 subjects were included and classified into four groups: healthy controls (n = 20), renal disease group (n = 20), AHF patients (n = 20), and patients with combined AHF and renal dysfunction (n = 20). Patients’ clinical, demographic, and laboratory data were recorded at the admission. Serum FGF23 and SuPAR were detected by ELISA, and NAG expression was analyzed by real-time quantitative PCR with internal control normalization. Statistical methods consisted of ANOVAs, Kruskal–Wallis analyses, chi-square tests, Spearman’s correlations, and receiver operating characteristic (ROC) curves, plus logistic regression with p < 0.05 indicative of statistical significance. Results The AUC of FGF-23 and SuPAR to differentiate AHF from renal disease was 0.792, with an accuracy of 82.5%, greater than those of the parameters. FGF23 and SuPAR well distinguished RIF-AHF (AUC > 0.96). The NAG gene performed at 100% sensitivity and specificity with an AUC of 1.0 to distinguish AHF, RD, and MCR from controls. The association of NAG concentration with inflammatory markers, acid–base disturbances, hypoxia indices, and renal function parameters indicated early tubular injury. NAG detected coincident clinical strata with excellent sensitivity even though its specificity was much lower. Conclusions FGF23, SuPAR, and NAG are strong discriminators of early-stage cardiorenal dysfunction in AHF. NAG gene expression, in particular, exhibits excellent diagnostic performance and mirrors important pathophysiological processes before conventional biomarkers. Admission, follow-up, and the response of these biomarkers to treatment could improve early diagnosis, risk stratification, and clinical management in patients with AHF and renal dysfunction.