Renal Pelvic Denervation Pilot Trial

Prior treatment

• Receiving dialysis treatment.
• Renal transplant recipient.
• Diabetes treated with SGLT2 inhibitor and/or GLP-1 agonist
• On any of the following medications: clonidine, guanfacine, or methyldopa.
• 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.
• Myocardial infarction, unstable angina, or stroke in the prior 6 months.
• Prior diagnosis of pulmonary hypertension, use of chronic oxygen therapy or need for mechanical ventilation
• On medications that affect blood pressure through off target effects, e.g., NSAIDs, steroids etc.
• Subjects who previously received device therapy for hypertension, including renal denervation.
• 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).
• History of chronic pain syndrome receiving ongoing therapy with narcotic and/or opiate therapy

Other illness

• History of non-compliance with medical care or medical treatments.
• History of atrial fibrillation.
• Untreated urinary tract infection.
• Polycystic kidney disease.
• Known secondary causes of hypertension such as adrenal disease, renal artery stenosis, renovascular hypertension.
• Type I diabetes mellitus.
• Stenotic valvular heart disease for which reduction of blood pressure would be hazardous.
• History of symptomatic heart failure
• Surgically correctable valvular heart disease.
• Peripheral arterial disease manifest clinically by claudication or non-healing ulcers.
• Any medical condition (including psychiatric disease) that would interfere with conducting the study or would not be in the best interest of the subject.
• Uncorrected bleeding diathesis
• 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).
• Subjects currently enrolled in another hypertension trial.
• History of narcotic / opiate drug abuse
• Active uroepithelial cancer
• Conditions that could potentially interfere with accuracy of blood pressure measurements
• Urinary tract anomalies or primary (FSGS) or secondary (e.g., Diabetic nephropathy) renal disease

Lab values

• Persistent albuminuria (urine with 30-300 mg albumin/g creatinine)
• Glomerulonephritis or interstitial nephritis or eGFR \<45 ml/min/1.73m2.

Other

• 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).
• Office SBP ≥180 and DBP ≥110 mmHg.
• 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.
• Pre-existing hydronephrosis, presence of renal calculi or ectopic, pelvic or ptotic kidney(s).
• Presence of only one kidney, or patients with dominant unilateral kidney function with one kidney split function less than 35%
• Focal sclerosing glomerulosclerosis.
• Evidence in medical history or at screening of hyperaldosteronism, defined as aldosterone/renin activity \> 30 or aldosterone level \>15 ng/dL
• Echocardiographic evidence of dilated, infiltrative or hypertrophic cardiomyopathy or intracardiac mass.
• Presence of severe obstructive sleep apnea not treated adequately by CPAP at screening.
• Life expectancy \< 24 months for any reason (investigator determination).
• Works night shifts.
• Upper arm circumference \> 20".
• Artificial urinary sphincter or penile prosthesis implanted.
• Planned medical procedures that could potentially interfere with measurement of blood pressure or assessment of any safety/effectiveness endpoints within 12 months of randomization
• Vulnerable subject populations (e.g., incarcerated or cognitively challenged adults).
• Pre-existing urological abnormalities such as hydronephrosis, ureteral vesicular reflux (congenital or acquired), neoplasia, etc.

• 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.
• Stable antihypertensive medical regimen for at least 30 days.
• Ambulatory mean daytime SBP ≥135 mmHg.
• Ambulatory daytime SBP \<170 and DBP \<105 mmHg.
• Office systolic SBP ≥140 mmHg and \<180.