MSC for Occlusive Disease of the Kidney

Mayo Clinic

Status and phase: Completed; Phase 1

Conditions: Ischemic Nephropathy; Renovascular Hypertension; Atherosclerotic Renal Artery Stenosis

Treatments: Drug: Arterial infusion of autologous mesenchymal stem cells

Study type: Interventional

Funder types: Other

Identifiers

NCT01840540

12-009298

Details and patient eligibility

About

To determine the safety and toxicity of intra-arterial infused autologous adipose derived mesenchymal stromal (stem) cells in patients with vascular occlusive disease of the kidney.

Full description

Individuals with unilateral arterial occlusive disease will be treated to injured kidney with autologous cells.

Enrollment: 6 patients

Sex: All

Ages: 40 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

4.1 Inclusion Criteria

1. Are between ages 40 and 80 years old.
2. Advanced vascular occlusive disease (atherosclerosis) affecting one or both kidneys: defined as a) loss of parenchymal volume and renal blood flow (measured by MDCT as previously described (17) and/or duplex ultrasound velocity above 300 cm/sec to the affected kidney to be infused with MSC's.
3. Have serum creatinine below 2.5 mg/dL
4. Have no-contraindications to angiography: severe contrast allergy
5. Have no contraindications to MR evaluations: e.g. pacemaker or magnetically active metal fragments, claustrophobia
6. Ability to comply with protocol
7. Competent and able to provide written informed consent

4.2 Exclusion Criteria

1. Advanced CKD: Stage 5 (two kidney eGFR < 15 ml/min/1.73 m2) contralateral renal artery occlusion/stenosis above 75% or ESRD requiring dialysis

2. Clinically significant abnormalities on laboratory examination, including Bilirubin (> 2 x normal), platelets (<100 thousand), potassium (>5.5 mEq/L), and sodium (<130 mEq/L), ALT or AST more than 2 x normal, Prothrombin time (INR>1.4), Hemoglobin <10.0 g/dL.

3. Clinically significant medical conditions within the six months before administration of MSCs: e.g. myocardial infarction, active angina, congestive heart failure) that would, in the opinion of the investigators, compromise the safety of the patient.

4. Specific exclusions:

   1. Clinical history of deep vein thrombosis within three months of MSC administration
   2. Uncontrolled hypertension (Systolic BP >180 mmHg despite therapy)
   3. Active infection
   4. Reduced ejection fraction (below 30%)
   5. Evidence of hepatitis B,C, or HIV
   6. Diabetes treated with insulin and/or glucose lowering agents
   7. Anemia (Hgb<10 g/dL)
   8. Regular use of potentially renotoxic drugs, e.g. non-steroidal anti-inflammatory agents (NSAID's): (>2 x weekly)

5. History of cancer including melanoma (with the exception of localized skin cancers)

6. Investigational drug exposure within thirty (30) days of baseline

7. Beck's depression score above 16

8. Pregnant or breast feeding.

9. History of clinically significant auto-immunity or any previous example of fat-directed autoimmunity

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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6 participants in 1 patient group

infusion of autologous mesenchymal stem cells

Experimental group

Description:

Patients will undergo a subcutaneous fat biopsy for expansion of mesenchymal stromal (stem) cells (MSC) in the Human Cell Therapy Laboratory. Patients will be admitted to the inpatient Clinical Research Unit of the Mayo Clinic Center for 3 days prior to treatment, for pre-infusion tests. Renal angiography will be performed to deliver a single intra-arterial dose of MSC's into one affected kidney. Patients will be observed for 24 hours for acute adverse events. Patients will have remote visits at 1 week, 4 weeks,8 weeks, and 6 months. At 3 months, patients will return for repeat evaluation of kidney function, blood flow and structural alterations within the clinical research unit at St. Mary's Hospital, Rochester, Minnesota. Thereafter, health assessment and blood draws will be repeated at 12 and 24 months with urinary cytology and MRI.

Treatment:

Drug: Arterial infusion of autologous mesenchymal stem cells