Inclusion Criteria:
1. Currently taking 2 anti-hypertensive medications (NOTE: no changes to medications allowed until after 2-month primary endpoint).
\- As recommended in ACC/AHA 2017 Guideline,2 subjects are to be taking one anti-hypertensive antagonizing the renin-angiotensin system, including ACE inhibitor, ARB or renin inhibitor. Second drug should either be a calcium channel blocker (amlodipine preferred) or a thiazide diuretic.
2. Stable antihypertensive medical regimen for at least 30 days.
3. Ambulatory mean daytime SBP ≥135 mmHg.
4. Ambulatory daytime SBP \<170 and DBP \<105 mmHg.
5. Office systolic SBP ≥140 mmHg and \<180.
Exclusion Criteria:
1. History of non-compliance with medical care or medical treatments.
2. History of atrial fibrillation.
3. Pregnant (verified with a urine or blood pregnancy test), breast-feeding, or planning to become pregnant. Note that all premenopausal women will be screened for pregnancy (see section 4.7.4).
4. Office SBP ≥180 and DBP ≥110 mmHg.
5. Untreated urinary tract infection.
6. Renal collecting system is compromised, such that the subject cannot undergo routine cystoscopy and retrograde pyelogram, as exemplified by duplicated collecting system, i.e., two or more ipsilateral ureters.
7. Pre-existing hydronephrosis, presence of renal calculi or ectopic, pelvic or ptotic kidney(s).
8. Receiving dialysis treatment.
9. Renal transplant recipient.
10. Presence of only one kidney, or patients with dominant unilateral kidney function with one kidney split function less than 35%
11. Polycystic kidney disease.
12. Diabetes treated with SGLT2 inhibitor and/or GLP-1 agonist
13. Persistent albuminuria (urine with 30-300 mg albumin/g creatinine)
14. Focal sclerosing glomerulosclerosis.
15. On any of the following medications: clonidine, guanfacine, or methyldopa.
16. Known secondary causes of hypertension such as adrenal disease, renal artery stenosis, renovascular hypertension.
17. Evidence in medical history or at screening of hyperaldosteronism, defined as aldosterone/renin activity \> 30 or aldosterone level \>15 ng/dL
18. Glomerulonephritis or interstitial nephritis or eGFR \<45 ml/min/1.73m2.
19. Type I diabetes mellitus.
20. Stenotic valvular heart disease for which reduction of blood pressure would be hazardous.
21. One or more episodes of orthostatic hypotension within the prior 6 months defined in section 6.6.2 as reduction of systolic blood pressure of ≥20 mmHg or diastolic blood pressure of ≥10 mm Hg within 3 minutes of standing.
22. Myocardial infarction, unstable angina, or stroke in the prior 6 months.
23. History of symptomatic heart failure
24. Echocardiographic evidence of dilated, infiltrative or hypertrophic cardiomyopathy or intracardiac mass.
25. Surgically correctable valvular heart disease.
26. Peripheral arterial disease manifest clinically by claudication or non-healing ulcers.
27. Any medical condition (including psychiatric disease) that would interfere with conducting the study or would not be in the best interest of the subject.
28. Prior diagnosis of pulmonary hypertension, use of chronic oxygen therapy or need for mechanical ventilation
29. Presence of severe obstructive sleep apnea not treated adequately by CPAP at screening.
30. On medications that affect blood pressure through off target effects, e.g., NSAIDs, steroids etc.
31. Uncorrected bleeding diathesis
32. Any clinical condition that can affect blood pressure or require the use of medications that can affect blood pressure (e.g., NSAIDs, steroids, cold remedies).
33. Life expectancy \< 24 months for any reason (investigator determination).
34. Works night shifts.
35. Upper arm circumference \> 20".
36. Subjects currently enrolled in another hypertension trial.
37. Subjects who previously received device therapy for hypertension, including renal denervation.
38. Subjects with a history of recurrent renal stones including episodes within the prior 6 months (subjects with first diagnosis of asymptomatic renal stone(s) at baseline/screening can be treated and rescreened at least one week following successful therapy of nephrolithiasis).
39. History of narcotic / opiate drug abuse
40. History of chronic pain syndrome receiving ongoing therapy with narcotic and/or opiate therapy
41. Active uroepithelial cancer
42. Artificial urinary sphincter or penile prosthesis implanted.
43. Planned medical procedures that could potentially interfere with measurement of blood pressure or assessment of any safety/effectiveness endpoints within 12 months of randomization
44. Conditions that could potentially interfere with accuracy of blood pressure measurements
45. Vulnerable subject populations (e.g., incarcerated or cognitively challenged adults).
46. Pre-existing urological abnormalities such as hydronephrosis, ureteral vesicular reflux (congenital or acquired), neoplasia, etc.
47. Urinary tract anomalies or primary (FSGS) or secondary (e.g., Diabetic nephropathy) renal disease
