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Hypoxia and Inflammatory Injury in Human Renovascular Hypertension

Watumiaji waliosajiliwa tu ndio wanaweza kutafsiri nakala
Ingia / Ingia
Kiungo kimehifadhiwa kwenye clipboard
HaliInatumika, sio kuajiri
Wadhamini
Mayo Clinic
Washirika
University of Mississippi Medical Center
University of Alabama at Birmingham

Maneno muhimu

Kikemikali

Current treatments for ARAS based on restoring blood flow alone have been unsuccessful at recovering kidney function. For this reason we are studying a stem cell product called "mesenchymal stem cells" or MSC. Mesenchymal stem cells (MSC) are grown from a person's own fat tissue (obtained as a fat biopsy) and infused back into the patient's own kidney.
This study is also being done to determine if the MSC infusion prior to percutaneous transluminal renal angioplasty with stenting (PTRA) further enhances changes in single kidney blood flow and restoration of kidney function, as well as to assess the relationship between MSC dose and measures of kidney function.

Maelezo

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.

Tarehe

Imethibitishwa Mwisho: 05/31/2020
Iliyowasilishwa Kwanza: 09/17/2014
Uandikishaji uliokadiriwa Uliwasilishwa: 10/12/2014
Iliyotumwa Kwanza: 10/16/2014
Sasisho la Mwisho Liliwasilishwa: 06/09/2020
Sasisho la Mwisho Lilichapishwa: 06/10/2020
Tarehe halisi ya kuanza kwa masomo: 09/30/2014
Tarehe ya Kukamilisha Msingi iliyokadiriwa: 08/31/2020
Tarehe ya Kukamilisha Utafiti: 08/31/2020

Hali au ugonjwa

Renal Artery Stenosis
Ischemic Nephropathy
Renovascular Disease
Chronic Kidney Disease

Uingiliaji / matibabu

Drug: Mesenchymal stem cell

Procedure: Mesenchymal stem cell delivery with stent placement

Awamu

Awamu 1

Vikundi vya Arm

MkonoUingiliaji / matibabu
Active Comparator: Mesenchymal stem cell delivery
To determine hemodynamic and immunologic changes associated with intra-renal delivery of adipose-derived MSC into human subjects with advanced RVD.
Active Comparator: Mesenchymal stem cell delivery with stent placement
To test adjunctive delivery of MSC to individuals with advanced RVD undergoing renal artery stenting.
Procedure: Mesenchymal stem cell delivery with stent placement
Intra-arterial stent placement after Mesenchymal stem cell infusion

Vigezo vya Kustahiki

Zama zinazostahiki Kujifunza 40 Years Kwa 40 Years
Jinsia Inastahiki KujifunzaAll
Hupokea Wajitolea wa AfyaNdio
Vigezo

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

Matokeo

Hatua za Matokeo ya Msingi

1. Change in Kidney function [3 months]

Renal Tissue oxygenation

2. Safety of Mesenchymal stem cell infusion [2 years]

Number of patients with tissue injury markers

Hatua za Matokeo ya Sekondari

1. Decrease in Kidney inflammation [3 months]

Venous and tissue biomarkers of inflammation

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