CKDu Treated With Intra-arterial Infusion of Autologous SVF Cells

Study Overview
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Brief Summary
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This is an interventional study to treat 18 patients with chronic kidney disease of unknown cause (CKDu), formerly known as Mesoamerican nephropathy (MeN), with autologous adipose tissue-derived stromal vascular fraction (SVF) cells transplanted by intra-arterial injection both kidneys. This study assesses: (1) safety and tolerability, (2) preliminary evidence of efficacy, (3) exploratory evidence of clinical effects.

Detailed Description
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Patients under go 24 hours of preoperative hydration combined with N-actyl cysteine 300 mg IV for prevention of nephrotoxicity. Under general anesthesia 200-300 cc of lipoaspirate is collected into a sterile processing cannister (GID SFV-1, Louisville, CO, USA). The tissue is washed and dissociated with collagenase (Worthington CLS-1, Lakewood, NJ, USA) at a concentration of 200 CDU/ml of total volume for 50 minutes at 39°C. This is followed by inactivation using 40 cc of human serum albumin. SVF cells are separated via centrifugation for 10 minutes at 800 g. The cell pellet is extracted and resuspended in Harmann solution with an aliquot (10 µl) removed for counting and viability assessment of resulting total nucleated cells (YNC) through and image cytometer (ADAM MC, Portsmouth NH, USA). Femoral artery catheterization is performed permitting advancement of a 100 cc balloon-tip catheter into the renal artery under fluoroscopic control, with position confirmation using 1 cc of OrtoRay® 320 contrast diluted 1:4 with Hartmann solution. SVF cells are then admixed with 200 cc Hartmann solution warmed to 37°C and in fused using a DRE infusion pump (DRE Medical, Louisville, KY, USA) over a 15 minute period with constant agitation. On the 1st pos-operative day creatinine and glomerular filtration rate are checked and the patient is discharged. Follow-up studies include clinical assessment, chemistries, and renal ultrasound to assess intra-parenchymal renal volume, renal blood flow distribution, and hilar artery vascular resistance.

Official Title
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Chronic Kidney Disease of Unknown Cause (CKDu) Treated With Directed Local Intra-arterial Infusion of Autologous Stromal Vascular Fraction (SVF) Cells.

Conditions
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Chronic Renal Failure of Unknown Cause

Intervention / Treatment
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* Genetic: Adipose-derived stromal vascular fraction cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Mesoamerican nephropathy Stages 3 and 4 No other renal disease No essential hypertension Exclusion Criteria: Significant abnormalities in laboratory tests that contraindicate surgical procedures. Acute pathology or complications of significant chronic pathologies in the 6 months prior to study entry, including, but not limited to: Medical history of deep vein thrombosis Uncontrolled hypertension Active infection Reduced cardiac ejection fraction Hepatitis B, C or HIV Diabetes treated with insulin or glucose lowering agents Anemia (Hb <9 g/dL) History of cancer Severe depression (Beck scale) Autoimmune disease

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bilateral Treatment<br>Intra-arterial injection of SVF cells into the kidneys. | Genetic: Adipose-derived stromal vascular fraction cells<br>* Kidney structural and functional changes in 18 patients after 36 months of treatment with SVF cells.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment related adverse events | Documentation of adverse events | 36-months follow-up post intervention. | 
| Preliminary evidence of efficacy | Improvement in clinical parameter of GFR as compared with historical age and stage-matched controls. | Assessment of changes between day 7 and month 36 post intervention. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal blood flow. | Distribution of intra-renal blood flow. | Up to month 12 post intervention. | 
| Kidney volume. | Changes in kidney size (cm3). | Up to month 12 post intervention. | 
| Renal arterial resistive index. | Decreases in hilar artery resistance index (less o equal to 0.7). | Up to month 12 post intervention. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stromal vascular fraction, Mesenchynmal stem cells, Chronic kidney disease, Adipose stem cells