Renal Artery Function and Histopathology Linked to Plasma and Fecal Metabolites in Heart Failure Patients.

Abstract

The gut microbiota and its associated host-microbe co-metabolites are increasingly recognized as key regulators of systemic metabolic balance and the cardiorenal axis, particularly within the context of cardiorenal syndrome. Although clinical evidence indicates that cardiac dysfunction may initiate or exacerbate renal pathological alterations, the key metabolic signaling molecules mediating the cardiorenal axis and their underlying mechanisms remain elusive. This study establishes a novel systematic research platform integrating cardiometabolic signatures with renal vascular function analysis, comprising: (1) Isolation and extraction of plasma/fecal metabolites from heart failure patients; (2) Ex vivo renal vascular isolation and primary culture techniques; (3) A multimodal evaluation framework for cardiorenal metabolic interactions, incorporating vascular functional assays, molecular biochemical tests for renal vascular injury markers, and histopathological analyses. Compared with healthy controls, metabolites from heart failure patients impaired renal vascular function and induced inflammatory responses, highlighting their potential as functional biomarkers in cardiorenal syndrome. This study does not focus on a specific metabolite; therefore, further identification and validation of the specific types of metabolites that exert pathogenic effects will be required in future studies using analytical techniques such as LC-MS/MS and NMR. Application of this platform revealed that cardiac disease-associated metabolites impair renal vascular function and homeostasis. These findings provide mechanistic insight into the metabolic drivers of cardiorenal interactions and offer a translational tool for identifying novel biomarkers and therapeutic targets.