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

Summary

Here, we present a protocol for developing a multimodal platform for elucidating cardiac metabolite-driven renal vascular dysfunction in cardiorenal syndrome.

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.

Introduction

Cardiorenal Syndrome (CRS) is a complex pathological condition characterized by bidirectional damage between the heart and kidneys. The intricate interdependence between these two organs was first described by Robert Bright in 1836, who systematically documented significant structural changes in the heart associated with advanced kidney disease¹. The prevalence of CRS is strongly linked to the coexistence of cardiovascular disease (CVD) and chronic kidney disease (CKD). Studies indicate that approximately 30% of heart failure patients also have CKD, while 44%-51% of deaths in CKD patients are directly attributed to cardiovascular events

Protocol

The experimental protocols and case methodologies employed in this study were ethically approved by the Urology Department at Peking University First Hospital (Ethical Review Code: 2023yan500-002) and Peking Union Medical College Hospital (approval No. I-23PJ585), with strict adherence to the principles outlined in the Declaration of Helsinki. For this study, we recruited male or female patients hospitalized in Peking Union Medical College Hospital (PUMCH) from July 2019, diagnosed with heart failure (HF) by at least two experienced cardiologists. A total of four HF patients (HF1-HF4) were included for plasma and fecal metabolite extraction. Written informed consent w....

Results

The cohort consisted of two females and two males, with an age range of 46 to 73 years (mean age: 64.0 years). Baseline blood pressure measurements showed systolic blood pressure ranging from 109 to 168 mmHg and diastolic pressure from 68 to 115 mmHg. All HF patients had recorded medication histories, including common cardioprotective agents such as beta-blockers, statins, and antiplatelet drugs, with individual variations in renin-angiotensin system inhibitors and diuretics. For controls, we recruited four subjects with.......

Discussion

Recent research in CRS has identified metabolic reprogramming as a key pathological mechanism, with metabolites regulating renal vascular homeostasis^7,8,9. While VSMCs play a critical role in regulating vascular tone and compliance in CRS, our study provides direct evidence that cardiac injury-associated metabolites impair vascular smooth muscle contractility and structural integrity. Specifically, our findings demonstrate that .......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
DMEM High Glucose	Gibco	Cat# 06-1055-57-1-ACS
PBS	Solarbio	Cat# P1010
Penicillin-Streptomycin-amphotericin B	Thermo Fisher Scientific	Cat# 15240062
Phenylephrine	MCE	Cat#HY-B0769
Reverse transcription system	Promega	Cat# A5001
Stereomicroscopic system	Leica	M80
SYBR Green master mix	Thermo Fisher Scientific	Cat# 4309155
Vascular tension measurement system	DMT	620M