MSC for Occlusive Disease of the Kidney

Phase I Study of Autologous Mesenchymal Stem Cells in the Treatment of Atherosclerotic Renal Artery Stenosis

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.

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

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