Adipose-derived MSC to Treat Rejection in Kidney Transplant Recipients

Exclusion Criteria32

• Nephrotic range proteinuria (≥ 3.5g/24h), detected more than once in the year preceding screening.
• History of post-transplant intervention for obstructive uropathy
• One or more of the following laboratory values:
• o Hemoglobin (Hb} ≤ 8 g/dL, Potassium (K) ≥ 5.5 mEq/dL, Alanine aminotransferase (ALT) ≥ 60 U/L, Hemoglobin A1C (HbA1c) ≥ 7%, International Normalized Ratio (INR) ≥ 2.0, Platelet count < 50 x 109/L (patients who receive a platelet transfusion to increase their platelet count will not be excluded).
• One or more of the following parameters:
• o Temperature ≥ 38°C (100.4°F), Respiratory rate ≥ 20/min, Oxygen saturation (SpO2) ≤ 90%, Systemic systolic blood pressure >160mmHg or < 100 mmHg, Pulse < 45/min or > 140/min
• Patients with the following grades/classes of vascular diseases:
• NYHA Class 3-4 CHF
• Uncontrolled arrhythmia, defined as: atrial fibrillation with rapid ventricular response, supraventricular tachycardia, Wolff-Parkinson-White syndrome, ventricular fibrillation, or sick sinus syndrome. Subjects with rate-controlled chronic atrial fibrillation will be allowed to participate.
• Cerebrovascular accident (CVA) within 90 days of screening
• Peripheral Arterial Disease (PAD), patients who have had prior vascular interventions for PAD in the index lower extremity.
• Acute illness within 30 days of screening.
• History of allergy or intolerance to iodinated contrast agents
• Women of childbearing potential or male subjects with female partners of childbearing potential unwilling to use an effective method of contraception during and for 12 months post-treatment.
• History of or current evidence of alcohol abuse, illicit drug use or dependence
• Active COVID 19 or positive test for the SARS-CoV-2 virus
• History of malignancy within 5 years of enrollment. History of adequately treated in-situ cervical carcinoma and/or adequately treated skin cancer (basal or squamous cell) will be permitted
• Serologic evidence of human immunodeficiency virus 1 or 2 infection
• Epstein Barr Virus (EBV) sero-negativity (EBV naïve)
• Cytomegalovirus (CMV) sero-negativity
• Active post-transplant opportunistic infections at the time of screening (CMV, BK virus, polyoma virus, EBV)
• Active Hepatitis B or Hepatitis C infection (e.g. NAT positive), and/or HBV core antibody positivity. Subjects with previously treated Hepatitis C (NAT negative, HCV IgG positive), or those with HBV surface antibody positive but HBV core antibody negative subjects will not be excluded from the study.
• Have received a kidney transplant from a Hepatitis C positive donor and plan to receive anti-viral treatment after transplant
• Any chronic condition for which anti-coagulation cannot be safely interrupted for kidney biopsy based on the CHA2DS2-VASc score of ≥ 6 risk stratum. If subjects fall into either the high or the moderate thrombotic risk, they will be deemed to be not safe to interrupt anticoagulation:
• High thrombotic risk: Mechanical heart valve: Any mitral valve prosthesis, any caged-ball or tilting disc aortic valve prosthesis, recent (within 6 months) stroke or transient ischemic attack; Atrial Fibrillation: CHADS2 score 5-6, CHA2DS2-VASc score 7-9, recent (within 3 months) stroke or transient ischemic attack, rheumatic valvular heart disease; Venous thromboembolism: Recent (within 3 months) VTE, severe thrombophilia (e.g. deficiency of protein C, protein S, or antithrombin; antiphospholipid antibodies; multiple abnormalities)
• Moderate thrombotic risk: Mechanical heart valve: Bileaflet aortic valve prosthesis and 1 or more of the of following risk factors: atrial fibrillation, prior stroke or transient ischemic attack, hypertension, diabetes, congestive heart failure; Atrial Fibrillation: CHADS2 score 3-4, CHA2DS2-VASc score 4-6; Venous thromboembolism: VTE within the past 3 to 12 months, non-severe thrombophilia (e.g. heterozygous factor V Leiden or prothrombin gene mutation), recurrent VTE
• For all other subjects, anticoagulation can be safely interrupted for 3 days prior to infusion and resumed a day after the infusion.
• Positive pregnancy test
• Participation in any other studies that involved investigational drugs or regimens in the preceding year
• Any other condition, in the investigator's judgment, that increases the risk of A-MSC infusion or prevents safe trial participation
• Unwilling or unable to adhere to study requirements and procedures
• Per Banff criteria category 6: the presence of other changes not considered to be caused by acute or chronic rejection, BK-Virus Nephropathy, Posttransplant Lymphoproliferative Disorder, Calcineurin Inhibitor Toxicity, Acute Tubular Injury, Recurrent Disease, De Novo Glomerulopathy (Other Than TG), Pyelonephritis or Drug-Induced Interstitial Nephritis