Transplanting Hepatitis C Kidneys Into Negative Kidney Recipients

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)