Patient-Derived Stem Cell Therapy for Diabetic Kidney Disease

Intra-arterially Delivered Autologous Mesenchymal Stem/Stromal Cell Therapy in Patients With Diabetic Kidney Disease: A Phase I Study

The Researchers will assess the safety, tolerability, dosing effect, and early signals of efficacy of intra-arterially delivered autologous (from self) adipose (fat) tissue-derived mesenchymal stem/stromal cells (MSC) in patients with progressive diabetic kidney disease (DKD).

This is a single center, open-label dose-escalating study assessing safety, tolerability, dosing effect, and early signals of efficacy of intra-arterially delivered autologous (from self) adipose tissue-derived mesenchymal stem/stromal cells (MSC) in 30 patients with progressive diabetic kidney disease (DKD). DKD will be defined as chronic kidney disease (CKD; estimated glomerular filtration rate; eGFR<60 mL/min/1.73m2) in the setting of diabetes mellitus (type 2; on anti-diabetes therapy) without overt etiologies of CKD beyond concomitant hypertension. Progressive DKD will be considered as eGFR 25-55 ml/min/1.73m2 with a) eGFR decline of 5 ml/min over 18 months or 10 ml/min over 3 years or b) an intermediate or high 5-year risk of progression to end-stage kidney failure (dialysis or transplant) based on the validated Tangri 4-variable (age, sex, eGFR, urinary albumin-creatinine ratio) kidney failure risk equation. Fifteen subjects will be placed in one of two cell dosage arms in a parallel design with single-kidney MSC administration at Day 0 and Month 3. Subjects will be followed a total of 15 months from time of initial cell administration.

Inclusion Criteria:

• Diabetes mellitus (on anti-diabetes drug therapy)
• Age 45-75 years
• eGFR 25-55 ml/min/1.73m2 at time of consent with: a) eGFR decline of 5 ml/min over 18 months or 10 ml/min over 3 years or b) an intermediate or high 5-year risk of progression to end-stage kidney failure (dialysis or transplant) based on the validated Tangri 4-variable (age, sex, eGFR, urinary albumin-creatinine ratio) kidney failure risk equation https://kidneyfailurerisk.com/
• Primary cause of kidney disease is diabetes without suspicion of concomitant kidney disease beyond hypertension
• Spot urine albumin:creatinine ≥30 mg/g unless on RAAS inhibition
• Ability to give informed consent

Exclusion Criteria:

• Hemoglobin A1c≥11%
• Pregnancy
• Active malignancy
• Active Immunosuppression therapy
• Kidney transplantation history
• Concomitant glomerulonephritis
• Nephrotic syndrome
• Solid organ transplantation history
• Autosomal dominant or recessive polycystic kidney disease
• Known renovascular disease
• Kidney failure (hemodialysis, peritoneal dialysis, or kidney transplantation)
• Active tobacco use
• Body weight >150 kg or BMI>50
• Uncontrolled hypertension: Systolic blood pressure (SBP) >180 mmHg despite antihypertensive therapy
• Recent cardiovascular event (myocardial infarction, stroke, congestive heart failure within 6 months
• Evidence of hepatitis B or C, or HIV infection, chronic
• Anticoagulation therapy requiring heparin bridging for procedures.
• History of methicillin-resistant staphylococcus aureus colonization
• Recent plastic, chemical or surgical manipulation of adipose tissue for cosmetic purposes within 6 months
• Inability to give informed consent
• Potentially unreliable subjects and those judged by the investigator to be unsuitable for the study