Transcutaneous Auricular Vagal Neuromodulation Therapy (AVNT™) in Chronic Kidney Disease Autonomic Dysfunction

Inclusion Criteria:

1. Age ≥18 years at time of informed consent
2. Documented Chronic Kidney Disease (CKD) stage G3-G5 (estimated Glomerular Filtration Rate (eGFR) 15-59 mL/min/1.73 m²), not on maintenance dialysis, based on eGFR or clinical documentation
3. Patients at New York University (NYU) clinics who meet criteria
4. Non NYU patients reaching out study team via iConnect
5. Clinically stable: No hospitalization, acute kidney injury, or acute illness requiring medical intervention within prior 4 weeks
6. Stable dosing of autonomically active medications: participants taking beta-blockers, other rate-controlling agents, anticholinergics, or sympathomimetics must be on a stable dose for ≥4 weeks before baseline with no anticipated changes during the study. Use of these agents is recorded and included as a covariate in analyses of heart-rate-based endpoints. Autonomically active medications: agents that materially affect heart rate, blood pressure, or autonomic tone - beta-blockers, non-dihydropyridine calcium-channel blockers, alpha-blockers, central sympatholytics (e.g., clonidine), midodrine, fludrocortisone, anticholinergics, sympathomimetics/stimulants, serotonin-norepinephrine reuptake inhibitors (SNRIs)/selective serotonin reuptake inhibitors (SSRIs), and diuretics are recorded with agent, dose, and timing, must be stable for ≥4 weeks before baseline with no anticipated change during the study, and are included as covariates. Home measurements are taken at a consistent time relative to the participant's usual dosing.

Exclusion Criteria:

1. Implantable cardioverter-defibrillator (ICD) or other implanted cardiac device

2. Known severe coronary disease (≥70% stenosis in major vessel) or myocardial infarction within past 5 years

3. Hospitalized within 4 weeks

4. Syncope or unexplained loss of consciousness within past 12 months

5. Uncontrolled arrhythmia (atrial fibrillation with resting heart rate >110 bpm, recent runs of sustained ventricular tachycardia or supraventricular tachycardia) within 3 months.

6. Severe bradycardia (<40 bpm at rest, symptomatic) , or second- or third-degree atrioventricular (AV) block without a functioning pacemaker

7. Neurological/Anatomical Exclusions:

8. History of vagotomy (surgical cutting of vagus nerve)

9. Trigeminal neuralgia within 1 year

10. Epilepsy or seizure disorder (unless well-controlled defined as seizure free with stable dose of medication for ≥2 years)

11. Dementia or cognitive impairment preventing informed consent or study compliance

    Renal/General Medical Exclusions:

12. End-stage kidney disease (ESKD) on maintenance hemodialysis or peritoneal dialysis

13. Pregnancy or breastfeeding

14. Active malignancy (except non-melanoma skin cancer)

15. Severe hepatic disease (Child-Pugh Class C cirrhosis)

16. Immunosuppression (within 8 weeks of enrollment) or active immunosuppressive therapy

    Skin/Electrode-Related Exclusions:

17. Active infection or severe lesions at tragus preventing electrode placement

18. Known allergy to gold or electrode materials

19. Implanted device at <2 cm proximity to ear tragus (e.g., cochlear implant, cerebral shunt, invasive Vagus Nerve Stimulation (VNS))

    Substance Use/Other:

20. Active substance uses disorder (within 1 year) or alcohol use >14 drinks/week

21. Participation in another clinical trial within 30 days

22. Any condition that, in the investigator's judgment, would make participation unsafe or preclude compliance

23. Prisoners