Beyond cardiac biomarkers: syndecan-1 as an early predictor of acute kidney and liver injury in patients with acute heart failure
R Miftode, O Mitu, A R Jigoranu, A F Oancea, A S Timpau, I L Miftode, I I Costache-Enache, A O PetrisAbstract
Introduction
Syndecan-1 is a less studied molecule in heart failure (HF), but its increased serum levels in patients with acute HF may potentially reflect important myocardial pathological changes, such as fibrosis, inflammation, or endothelial dysfunction. Beyond its role as a cardiac biomarker, syndecan-1 could exhibit a promising role as a surrogate predictor of early kidney injury, as it seems that syndecan-1 levels are not influenced by a decreased creatinine clearance, but rather by ongoing damage to the glycocalyx of the renal endothelium. Additionally, syndecan-1 is involved in fibrotic processes, both myocardial and hepatic, via its extramembrane domain with a role in matrix metalloproteinase synthesis.
Purpose
The study aimed to highlight the potential use of syndecan-1 in clinical practice as a diagnostic and prognostic biomarker in acute HF, especially from the perspective of acute liver and kidney injury.
Materials and methods
We analyzed the serum levels of syndecan-1 in 100 patients presenting in emergency with acute HF, compared to 53 patients with chronic HF (control group). For further assessment, we used a small venous blood sample (2 mL) that was centrifuged in order to separate the serum. Quantification of syndecan-1 was performed by ELISA method, using dedicated kits. Acute kidney injury (AKI) was defined according to RIFLE criteria. The acute liver injury assessment was based on at least a 2-fold increase in transaminases (compared the reference values of the hospital laboratory).
Results
Syndecan-1 exhibited significantly higher mean serum levels among patients with acute HF compared to the control group. ROC analysis exhibited a consistent predictive value for syndecan-1, mirrored by its AUC of 0.898, showing a statistically significant performance (p < 0.05) in predicting acute HF. Syndecan-1 was also significantly correlated with the need for positive inotropic support and with the use of non-invasive ventilation mode. However, mortality rates (both during hospitalization and 30 days after discharge) were not substantially associated with its serum concentrations. Concerning its role of a dual biomarker, we revealed positive and significant correlations between elevated syndecan-1 and liver transaminases, a similar pattern being found for the correlation with serum urea and creatinine. Moreover, an increased syndecan-1 at admission was significantly and directly correlated with increased markers of liver and kidney injury occurring during hospitalization, from initially normal baseline values.
Conclusions
Syndecan-1 may be used as a surrogate cardiac biomarker in acute HF, as its serum levels are significantly higher in those patients, compared to controls with chronic HF. Syndecan-1 also emerged as an early predictor of liver and kidney injury in patients admitted for acute HF, even before the increase of the classic markers of organ dysfunction, such as serum creatinine or liver transaminases.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.