Hypoxia and Inflammatory Injury in Human Renovascular Hypertension

These studies include participation by human subjects using a 3-day inpatient CRU protocol at St. Mary's Hospital. Studies include formal measurement of blood and urinary markers of kidney function, BOLD MR and multidetector CT scanning. Forty-two non-diabetic patients between 40 and 80 years of any race or ethnicity will be recruited. All will have hypertension (defined as BP≥140/90 mmHg or ongoing antihypertensive drug therapy) but will have less than 180 mmHg to be included (with or without drug therapy). These subjects will be free of cardiovascular events within 3 months and will not have implanted electrical devices, such as a pacemaker or defibrillator. All patients will have identified large vessel renovascular disease (RVD) for Aims 1, 2 and 3. At least 10% of these subjects will be of African-American descent (self-identified) and recruited in collaboration with the University of Mississippi under the direction of Dr. Luis Juncos and the University of Alabama under the direction of Dr. David Calhoun. For completion of Aims 2 and 3, a three-day evaluation will be repeated between three and four months later, and ongoing safety and imaging studies will be performed up to 24 months after MSC administration. Participants in these protocols will undergo transvenous kidney biopsy under the direction of Drs. McKusick and Misra and their colleagues in Interventional Radiology. All subjects for these studies will complete the research plan at Mayo Clinic, Rochester, Minnesota.

Inclusion criteria

• Creatinine <2.2 mg/dL for Caucasian males, <2.0 Caucasian females,< 2.4 African-American males, <2.1 mg/dL African-American females
• Hypertension (Systolic BP>155 mm Hg) and/or requirement for two or more antihypertensive medications: no restrictions on antihypertensive agents, although loop diuretics will be changed to diluting site agents (e.g. hydrochlorothiazide, indapamide, metolazone) prior to study.
• Angiotensin Converting Enzyme (ACE inhibitor) or Angiotensin Receptor Blocker (ARB) therapy maintained or initiated at usual recommended daily dose (equivalent: 40 mg lisinopril) .

Exclusion criteria

• Diabetes requiring insulin or oral hypoglycemic medications (see text)
• Known allergy to furosemide or iodinated intravenous contrast
• Pregnancy
• Recent Cardiovascular event: Myocardial infarction, stroke, congestive heart failure within 3 months
• Cardiac ejection fraction less than 30%
• Evidence of hepatitis B or C, or HIV infection
• requirement for potentially nephrotoxic drugs, e.g. non-steroidal anti-inflammatory drugs
• Uncontrolled hypertension: SBP >180 mm Hg, despite antihypertensive therapy
• Kidney transplant
• Pacemaker, implantable defibrillator or other contraindication to Magnetic resonance imaging
• Inability to comply with breath-hold for 30 seconds
• History of deep venous thrombosis within 3 months of enrollment
• contraindications to renal biopsy including artificial valve requiring continuous anticoagulation