Novel Cardiovascular Biomarkers in Patients With Kidney Disease

Chronic kidney disease (CKD) is a long-term condition where the kidneys do not work as well as they should. End-stage kidney failure (ESKD) is the final, irreparable stage of chronic kidney disease (CKD), where kidney function has worsened, so the kidneys can no longer function independently.

At this stage, dialysis is required to remove waste products and excess fluid from the blood. There are two types of dialysis. In haemodialysis (HD), blood is pumped out of the body to an artificial kidney machine and returned to the body by tubes that connect a person to the machine. In peritoneal dialysis (PD), the inside lining of the belly acts as a natural filter. PD has the advantage of being gentler on the heart. HD causes significant stress to the heart by reducing the blood flow to the heart muscle, resulting in heart failure, irregular rhythms, and eventually sudden heart death. A large observational study showed that HD patients had 48% worse survival in the first two years than PD patients.

Several molecules ('biomarkers') can be detected in blood and inform doctors of heart damage. Studying the form and function of proteins (Proteomics), including how they work and interact with each other inside cells in patients, could help identify the onset of heart problems. HD patients are also prone to body fat changes (cholesterol/lipids). Due to high cholesterol, there is build-up on the walls of arteries, causing their hardening. In HD patients, this process is faster due to abnormalities in lipid structure. Therefore, studying the heart biomarkers, protein, and lipid makeup of HD patients may help to find people at substantial risk of heart and vascular problems and if they are likely to become unwell due to these heart problems.

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Key information

Conditions

Haemodialysis Complication Cardiovascular Diseases Chronic Disease Disease Attributes Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Kidney Diseases Kidney Failure, Chronic Major Adverse Cardiac Events Male Urogenital Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Renal Insufficiency Renal Insufficiency, Chronic Urogenital Diseases Urologic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

About this study

Currently, there is no specific approach to stratify CV risk in HD patients; therefore, patients are not offered targeted preventative interventions. This novel project will characterise circulating biomarkers and proteomics of myocyte damage, cardiac stress, fibrosis, and inflammation, including lipid composition. Understanding the cardiac biomarkers, targeted proteomics and lipidomics in HD patients as early predictors of CV outcomes will help better decisions on treatment choices and earlier interventions to improve outcomes in these patients. Proteomics and lipidomics, analysed with machine learning techniques, may offer new opportunities to improve risk stratification in these patients. The successful introduction of novel agents, comprising proprotein convertase subtilisin-like/kexin type 9 inhibitors, low-dose oral anticoagulants, sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 agonists, anti-inflammatory agents, and icosapent ethyl, offers an opportunity to reduce the burden of recurrent CV risk further based on their risk stratification. This study aims to obtain pilot data for promising cardiac biomarkers, proteomics and lipidomics, validating them against control groups and establishing prospective changes of the new markers and their relation to the major adverse cardiac events (MACE).

Study Objectives

To determine circulating plasma levels of new cardiac biomarkers (cMyC, galectin 3) in incident HD patients by comparing them to control groups (PD and CKD 3-4 (not on dialysis)) and to correlate with traditional biomarkers (hsTnT).
To evaluate the lipidome as a marker of CVD risk in incident HD patients by studying the indices of HDL quality and quantity, including HDL-particle number, HDL cholesterol, apolipoprotein (apo) A-I levels, serum amyloid A (SAA) content and HDL-cholesterol efflux capacity, and paraoxonase activity of apoB-depleted serum.
To evaluate proteomic signature as a marker of cardiac disease risk in incident HD patients by studying the proteomic platform of untargeted high-value proteins for CVD risk (as an exploratory analysis).
To explore the association between proposed cardiac biomarkers, proteomics, lipidome and MACE (as an exploratory analysis).

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Patients aged≥45 years (or ≥18 with a history of diabetes). b. Cases: Incident haemodialysis patients c. A comparative arm of peritoneal dialysis patients and CKD 3-4 (not on dialysis) with hypertension as a key risk factor for CVD.

d. Capable of understanding the purpose and risks of the study, fully informed, and given informed consent.

Exclusion criteria

Patients with pre-existing heart disease will be excluded.
Patients with active cancer.

Treatment and study plan

Cardiac biomarkers

Diagnostic Test

Blood samples will be collected at baseline (within 6 weeks of dialysis start), at 6 months post-commencement and 12 months post-commencement of haemodialysis. The blood sampling will be mid-week samples taken at the dialysis start for haemodialysis patients, with a similar approach for the PD controls. For the CKD controls, the blood samples will be scheduled around routine clinic attendance, adhering where possible to the time intervals for HD cases and PD controls.

Lipidomics

Diagnostic Test

Proteomics

Diagnostic Test

Primary outcomes

Major Adverse Cardiac Events

Time frame: 12 months

An exploratory analysis of all-cause mortality and Major Adverse Cardiac Events (MACE). MACE is defined as a composite of CV death, Ischemic Heart Disease (IHD), myocardial infarction (MI), stroke/TIA, Heart Failure, Cardiac revascularisation (percutaneous coronary intervention and coronary artery bypass graft), carotid endarterectomy. The follow-up will be 12 months for all patients. This will be correlated with biomarker, proteomic and lipidomic data.

Study contacts

Contact information is provided by the study sponsor or research team.

Anirudh Rao, PhD

CONTACT

[email protected]

01517063487

Sponsors and collaborators

Lead sponsor

Liverpool University Hospitals NHS Foundation Trust

Other Gov

Registry information

Acronym: CBKD

Important dates

Study start: 2023
Primary completion: 2025
Study completion: 2026
First posted: Sep 14, 2023
Registry last updated: Sep 18, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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