Nephrology-Hypertension Clinical Trials

• ≥ 18 years of age
• Patient is able to provide written informed consent
• Meet criteria for one of following patient populations:

• CKD

• eGFR ≥30 and <90 ml/min/1.73m2 by CKD Epidemiology Collaboration (CKD EPI) equation17 (with or without history of hypertension)

• Urine albumin to creatinine ratio (UACR) ≥ 30mg/g creatinine

• eGFR <30 ml/min/1.73m2 by CKD Epidemiology Collaboration (CKD EPI) equation (with or without history of hypertension AND with no UACR requirement)

• ESRD

• Currently receiving dialysis (hemodialysis or peritoneal dialysis)

• No eGFR or UACR requirement

• Healthy volunteer

• No prior history of kidney disease (as defined by eGFR >60 ml/min/1.73m2 by CKD Epidemiology Collaboration (CKD EPI) equation and UACR <30 mg/g creatinine, based on Screening Visit lab results or average between local lab results (collected within 3 months from the date of the Screening Visit) and lab results from Screening Visit.

• No self-reported history of hypertension, diabetes mellitus, liver disease, or cardiovascular disease

• CKD-Biopsy

• eGFR <90 ml/min/1.73m2 by CKD EPI equation

• Urine albumin to creatinine ratio (UACR) ≥30 mg/g creatinine

• Undergoing a clinically indicated renal biopsy

• Transplant Kidney Biopsy

• Kidney transplant recipient undergoing a protocol surveillance transplant kidney biopsy

EXCLUSION CRITERIA:

• Known hypersensitivity to sulfur hexafluoride lipid or to any component of Lumason®
• Known severe pulmonary hypertension (pulmonary artery pressure > 75mmHg)
• Active cardiac disease including any of the following:

• Unstable angina
• Myocardial infarction within 48 hours prior to date of proposed Lumason® administration
• Severe arrhythmia (ventricular tachycardia, uncontrolled atrial fibrillation with rapid ventricular response, torsades de pointes)

• Escalating vasopressor requirements in prior 24 hours
• Recent neurological compromise (i.e. cerebrovascular accident including transient ischemic attacks within 3 months of Lumason® administration)

• Emergency cardiac surgery
• BMI ≥ 35 kg/m2
• Clinical signs of acute rejection as the indication for transplant kidney biopsy
• Inability for patient or patient’s surrogate to provide informed consent
• Pregnancy
• Incarcerated individuals

Inclusion criteria for all: >18 years of age

Inclusion criteria for CKD: eGFR 20-60 ml/min/1.73m2 on stable doses of diuretics and/or angiotensin converting enzyme inhibitor or angiotensin receptor blocker, unless contraindicated.

Inclusion criteria for the non-CKD group: eGFR >60 ml/min/1.73m2 and UACR <30 mg/g.

Exclusion criteria for all: presence or history of diabetes, coronary revascularization within the last 6 months, hemodynamically significant valvular disease, significant lung disease requiring home oxygen, angina, non-revascularized myocardial ischemia, systolic BP <100 or >180 mmHg, pregnancy, clinical HF symptoms, history of systemic disease processes that can cause HFpEF, such as amyloidosis or sarcoidosis, any musculoskeletal or chronic condition that will interfere with completion of cardiac testing, or active cancer, immunosuppressive therapy. Participants will also be excluded from continuing in the study if the pre-exercise echocardiogram demonstrates a reduced ejection fraction ≤50% or hemodynamically significant valvular disease at the baseline study visit.

Exclusion criteria for the non-CKD group: eGFR <60 ml/min/1.73m2 and UACR >30 mg/

Exclusion criteria for CKD: currently on sodium glucose cotransporter 2 inhibitor (SGLT2i) therapy, SGLT2i hypersensitivity, liver disease, ALT/AST> 3x normal, history of recurrent urinary tract infections (in the opinion of the investigator) or a urinary tract infection in the last 3 months.

Biopsy-proven Membranous, Minimal Change, FSGS, or IgAN within 5 years of study enrollment

-Diagnosed with IgAN, as demonstrated by renal biopsy conducted within the past 10 years

-Urine protein excretion >1g/24 hours, or UPCR >1.0mg/mg based on 24 hour urine collection

-Stable dose of RAASi for 12 weeks at screening

-Blood pressure <150/90

-eGFR >30 mL/min/1.73m2

Biopsy Confirmed Lupus Nephritis

eGFR > 30

UPCr(ideally based on 24 hour urine collection) > 0.75mg/mg

Biopsy confirming Primary Membranous Nephropathy within 5 years

eGFR >40

UPCr(ideally based on 24 hour urine) of 3.5g/g