Transplanting Hepatitis C Kidneys Into Negative Kidney Recipients (THINKER)

This is an interventional treatment trial for End Stage Renal Disease focused on measuring end-stage renal disease Read More

Subject:

Inclusion criteria

• Must be waitlisted for a kidney transplant (dialysis is not a requirement if a patient is waitlisted)
• Listed for an isolated kidney transplant with ≤2555 days of accrued transplant waiting time and/or ≤2555 days of dialysis time for blood group A, B, or O, by enrollment
• Listed for an isolated kidney transplant with ≤1825 days of accrued transplant waiting time and/or ≤1825 days of dialysis time for blood group AB, by enrollment
• No available living kidney donor
• Between 30-70 years of age, by enrollment
• Have a panel reactive antibody level ≤97%
• eGFR <15ml/min/1.73m2 as calculated using the 4 variable MDRD equation
• Obtained agreement for participation from the patient's treating transplant nephrologist
• Able to travel to the University of Pennsylvania for routine post-transplant visits and study visits for a minimum of 6 months after transplantation
• No active illicit substance abuse
• Weigh at least 50kg
• Women must agree to use birth control in accordance with Mycophenolate Risk Evaluation and Mitigation Strategy (REMS) following transplant due to the increased risk of birth defects and/or miscarriage
• Both men and women must agree to use at least one barrier method to prevent any secretion exchange
• Inclusion criteria for treatment (not for entry as study patient) will include any detectable HCV RNA
• Able to provide informed consent

Exclusion criteria

• Hepatocellular carcinoma
• Patients with primary focal segmental glomerulosclerosis (FSGS), FSGS recurring after previous transplant, or disease process with increased risk of causing early graft failure as per the treating nephrologist
• HIV positive
• HCV RNA positive (can be isolated HCV antibody positive provided the subject has no history of previously treated HCV)
• Hepatitis B surface antigen positive
• Any other chronic liver disease (excluding non-alcoholic fatty liver disease (NAFLD) with abnormal liver enzymes
• Persistently elevated liver transaminases
• Significant hepatic fibrosis on screening elastography (≥f2 fibrosis)
• Pregnant or nursing (lactating) women
• Known allergy or intolerance to tacrolimus that would require post-transplant administration of cyclosporine, rather than tacrolimus given the drug-drug interaction between cyclosporine and Zepatier
• Waitlisted for a multi-organ transplant (e.g., pancreas-kidney, heart-kidney, etc.)

• Significant cardiomyopathy defined as either:

  • Left ventricular ejection fraction <40% on most recent echocardiogram
  • Left ventricular ejection fraction ≥40% but <50% on most recent echocardiogram with an <5 METS of exercise tolerance
  • Reversible ischemia on stress testing without revascularization

Donor Organ Selection:

Inclusion Criteria

• Detectable HCV RNA
• Age ≤60 years
• Study modified Kidney donor profile index (KDPI) score ≤0.856 - calculated as if the kidney were HCV-negative (https://optn.transplant.hrsa.gov/resources/allocation-calculators/kdpi-calculator/)

Exclusion Criteria

• Anatomical issues in the kidney allograft that raise the risk of post-transplant complications (e.g., number or length of renal arteries or veins)
• Confirmed HIV positive
• Confirmed HBV positive (positive Hepatitis B surface antigen and/or HBV DNA)
• Known previously failed treatment for HCV using a regimen with a direct-acting antiviral (can have received interferon monotherapy and/or interferon + ribavirin combination therapy)