Transplantation of Kidneys From Hepatitis C–Infected Donors to Hepatitis C–Negative Recipients

Single Center Experience

Miklos Z. Molnar; Satheesh Nair; Orsolya Cseprekal; Masahiko Yazawa; Manish Talwar; Vasanthi Balaraman; Pradeep S.B. Podila; Valeria Mas; Daniel Maluf; Ryan A. Helmick; Luis Campos; Nosratollah Nezakatgoo; Corey Eymard; Peter Horton; Rajanshu Verma; Ann Holbrook Jenkins; Charlotte R. Handley; Heather S. Snyder; Carolyn Cummings; Uchenna A. Agbim; Benedict Maliakkal; Sanjaya K. Satapathy; James D. Eason

Disclosures

American Journal of Transplantation. 2019;19(11):3046-3057. 

In This Article

Abstract and Introduction

Abstract

Our aim was to evaluate the safety of transplanting kidneys from HCV-infected donors in HCV-uninfected recipients. Data collected from 53 recipients in a single center, observational study included donor and recipient characteristics, liver and kidney graft function, new infections and de novo donor-specific antibodies and renal histology. Treatment with a direct-acting antiviral regimen was initiated when HCV RNA was detected. The mean ± SD age of recipients was 53 ± 11 years, 34% were female, 19% and 79% of recipients were white and African American, respectively. The median and interquartile range (IQR) time between transplant and treatment initiation was 76 (IQR: 68–88) days. All 53 recipients became viremic (genotype: 1a [N = 34], 1b [N = 1], 2 [N = 3], and 3 [N = 15]). The majority (81%) of recipients did not experience clinically significant increases (>3 times higher than upper limit of the normal value) in aminotransferase levels and their HCV RNA levels were in the 5 to 6 log range. One patient developed fibrosing cholestatic hepatitis with complete resolution. All recipients completed antiviral treatment and 100% were HCV RNA–negative and achieved 12-week sustained virologic response. The estimated GFRs at end of treatment and 12-week posttreatment were 67 ± 21 mL/min/1.73 m2 and 67 ± 17 mL/min/1.73 m2, respectively. Four recipients developed acute rejection. Kidney transplantation from HCV-infected donors to HCV-negative recipients should be considered in all eligible patients.

Introduction

The continuing disparity between demand and supply of kidneys for transplantation has pressured the transplant community to utilize Public Health Service (PHS) increased infectious risk donors including donors with hepatitis C (HCV). HCV donor antibody and nucleic acid test (NAT)–positive kidneys have historically been offered only to recipients with HCV ribonucleic acid (RNA)/antibody positivity. This practice is supported by data that demonstrates HCV RNA–positive recipients can significantly reduce their wait times if they are willing to accept HCV NAT–positive kidneys.[1,2] These shortened wait times lead to an overall improvement in mortality in this patient population;[3] however, 65% of all HCV antibody–positive kidneys procured with the intent of transplantation between 2005 and 2014 were discarded, which included more than 4000 HCV kidneys.[4] The previous reluctance to use HCV antibody–positive kidneys stemmed from the fear of HCV-related complications in absence of effective treatment options.[4] Now, the availability of highly effective direct-acting antiviral agents (DAAs) with high cure rates above 95% may allow for better utilization of these kidneys.[5–7]

In addition, prior cost-effectiveness studies indicate that transplanting HCV-infected donor kidneys to naïve recipients results in lower total healthcare costs compared to additional dialysis time incurred while waiting for HCV-negative donor kidneys.[8,9] These results raise the question of whether HCV-infected donor kidneys should be used more liberally, which includes transplanting them into HCV uninfected recipients.[10]

Two recent, small clinical trials have assessed the feasibility of transplantation of kidneys from HCV-infected donors to HCV-negative recipients.[11–13] The Transplanting Hepatitis C Kidneys into Negative KidnEy Recipients (THINKER) study was an open-label, nonrandomized trial that included 20 HCV–negative recipients who received kidney grafts from HCV-infected (NAT-positive) donors. All patients were started on HCV treatment within 5 days after transplantation and all achieved sustained virologic response (SVR) at 12 weeks after completion of treatment.[11] A slightly different, prophylactic approach was studied in Exploring Renal Transplants Using Hepatitis C Infected Donors for HCV-Negative Recipients (EXPANDER) which was an open-label, small, nonrandomized clinical trial.[13] This trial included 10 HCV-uninfected recipients who received HCV NAT–positive kidneys.[13] Patients were started on antiviral therapy before transplantation and were continued on a specified DAA regimen for a total of 12 weeks posttransplant.[13] All recipients were virus-free at the end of treatment and 12 weeks posttransplant.[13] Although these clinical trials showed positive outcomes, they were small and included carefully selected recipients. Additionally, DAA was supplied by pharmaceutical companies. In clinical practice, it is highly unlikely that DAA will be covered by a third party payer without evidence of active HCV infection (such as the protocol used in the EXPANDER trial). Even after these small feasibility studies, it is unknown if the transplantation of kidneys from HCV-infected donors to HCV-negative recipients can be performed as the standard of care outside of clinical trials.

To address this knowledge gap, we aimed to investigate the feasibility and safety of transplantation of kidneys from HCV-infected donors to HCV-negative recipients as the standard of care, outside of clinical trials, using our center's experience. The goal of this retrospective cohort study was to provide descriptive, clinical information regarding liver-related, kidney graft-related, and transplant-related complications to introduce our practice as a potential standard of care for other centers in the United States. Additionally, this study aimed to demonstrate how allocation of HCV-positive kidneys would change if a modified, so-called optimal, Kidney Donor Profile Index (KDPI) score was utilized.

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