A trial of transplanting Hepatitis C-viremic kidneys into Hepatitis C-Negative kidney recipients (THINKER-NEXT)

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Project Summary/Abstract Kidney transplant extends life, improves quality of life, and reduces healthcare costs. Unfortunately, the waiting list exceeds 94,000 people while only approximately 14,000 deceased donor kidney transplants (DDKT) occur annually and many patients wait >5 years for a DDKT. For the elderly and some other patient groups, it is common to die waiting. Yet, nearly 600 kidneys from donors infected hepatitis C virus (HCV) were discarded in 2018 (50.1% of the total number of kidneys from HCV-viremic donors); hundreds more kidneys are never procured because of the perception that no center will accept them. Early successes of pilot clinical trials and single-center series of transplanting kidneys from HCV-viremic donors have demonstrated the potential for this practice to increase the number of lifesaving kidney transplants by more than 1,000 kidney transplants each year. However, the dominant system for assessing kidney quality also applies a lower quality score to any kidney from an HCV-viremic donor, thereby promoting organ discard. Also, early experiences from uncontrolled studies without well-matched comparator groups has led to reports of unexpected complications and/or higher than anticipated rates of treatment failures that underscore the need for a formal multi-center clinical trial. Recent reports have highlighted a series of post-transplant complications that necessitate evaluation in a large multi-center trial, for example: a) fibrosing cholestatic HCV in several HCV-negative recipients of an HCV-viremic donor; b) increased incidence of CMV viremia in recipients of HCV-viremic kidneys; and c) membranoproliferative glomerulonephritis. While these complications are rare, they underscore the view from transplant leaders, including the American Society of Transplantation, the American Association for the Study of Liver Diseases, and the Infectious Disease Society of America that this practice is considered `experimental' and is best performed under IRB-approved protocols with rigorous informed consent and assurances of access to HCV treatment. Furthermore, despite increased transplantation of kidneys from HCV- viremic donors into HCV-negative patients, there remain persistent knowledge gaps that need to be addressed for this practice to be accepted as routine clinical care from the perspective of patients, providers, and payers. This multi-center trial seeks to provide significant knowledge gaps that remain by addressing these specific aims: a) estimate HCV cure rates in HCV-negative recipients of HCV-viremic kidneys with a narrow confidence interval; b) determine whether consenting to receiving an HCV-viremic kidney improves survival; c) evaluate 1- year renal function of HCV-viremic kidneys compared to matched comparators; d) assess whether HCV- negative recipients of HCV-viremic kidneys have increased risks of CMV infection; and e) determine if the prevalence of chronic kidney disease pathology is similar in HCV-viremic vs HCV-negative kidney donors. The overarching goal is to determine if kidneys from HCV-viremic donors can safely be transplanted into HCV- negative patients with end-stage renal disease.