Challenges of Biomarker Application in Patients with Cardiorenal Syndrome

Background/Objectives: Cardiorenal syndrome (CRS) is associated with substantially higher morbidity and mortality than either isolated cardiac or renal dysfunction. The application of classical and novel biomarkers has been tested in prompt diagnosis and monitoring of patients with CRS. Methods: This is a comprehensive literature review following a structured approach. We searched MEDLINE and Embase databases from January 2000 to December 2025. Results: The pathophysiology of CRS is complex, and the present review attempts to shed light on the clinical interpretation of the most widely used biomarkers as indices of diagnosis and prognosis. Among them, troponin is elevated in CRS and its absolute levels retain prognostic value, while changes in its levels over time may assist in the diagnosis of acute coronary syndrome. Natriuretic peptides are highly influenced by coexistence of chronic kidney disease (CKD) and in this context have considerable diagnostic and prognostic value. The combination of cystatin C, a biomarker of renal dysfunction, with cardiac biomarkers may create a powerful risk algorithm. Most recently, gene profiling and proteomics have the potential to stratify patients with CRS; however, more data from large cohorts are required for their validation. The therapeutic modulation of biomarkers in CRS patients may help elucidate the underlying pathophysiologic mechanisms. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have emerged as first-line therapy for patients with CRS, despite the fact their mechanisms are mostly unknown. Significant changes in the aforementioned biomarkers and the inflammatory factors may explain their emerging beneficial effects on both heart failure and CKD. Conclusions: The use of biomarkers has increased rapidly in recent years for diagnosis, surveillance and prognostic stratification in CRS.