Despite more than 90,000 patients waitlisted for a kidney transplant, 21.3% of donated kidneys were not used according to the 2020 Annual Data Report of the Scientific Registry of Transplant Recipients and Organ Procurement and Transplant Network (1). As organ demand far exceeds supply, transplant professionals strive to break barriers and improve utilization of available kidneys (2, 3). Seminal studies, such as Transplanting Hepatitis C Kidneys into Negative Kidney Recipients (THINKER) (4) and Exploring Renal Transplants Using Hepatitis C Infected Donors for HCV-Negative Recipients (EXPANDER) (5), have transformed the way we use kidneys from donors who are hepatitis C virus (HCV) positive. The combination of novel direct-acting antiviral (DAA) therapies for HCV, with cure rates approaching 100% (6), and the unfortunate rise in opioid overdose-related mortality of young individuals (7) has translated into an unanticipated opportunity for those with chronic kidney disease (CKD) who are waitlisted for a kidney transplant (8). The dramatic change in praxis as it relates to utilization of HCV-positive kidneys for transplantation is shown in Figure 1A.
Transplantation of HCV-positive kidneys
Citation: Kidney News 15, 9
Data are based on deceased donor kidney transplants performed in the United States between April 1, 2015, and December 31, 2022, provided by the Organ Procurement and Transplantation Network on May 10, 2023. NAT, nucleic acid testIn the article entitled “Kidney transplantation from hepatitis C virus-infected donors to uninfected recipients: A systematic review for the KDIGO [Kidney Disease: Improving Global Outcomes] 2022 hepatitis C clinical practice guideline update” by Gordon and colleagues (9), the authors performed a systematic review on the use of donors who are HCV viremic for kidney transplantation into recipients who are HCV naïve (donor [D]+/recipient [R]–). Sixteen investigations of HCV D+/R– kidney transplantation, comprising 557 patients, were evaluated using a specified protocol for DAAs. Sustained viral response at 12 weeks was reported in all studies and was achieved in 97.7% of patients (95% confidence interval [CI], 96.3%–98.8%). Although a shorter course of DAAs resulted in high rates of viremia, those who remained viremic after the initial treatment achieved viral clearance following retreatment. Serious adverse events were reported in 69% of the studies and were uncommon at a rate of 0.4% (95% CI, 0.1%–2.8%). Three cases of fibrosing cholestatic hepatitis were reported among 211 patients, two with a delayed start of DAA therapy; all three had complete resolution.
The mortality at 1-plus year was 2.1%, and the data appeared to be similar to the outcome in HCV D–/R– transplants. One-year kidney graft survival was 97.6%, similar to HCV D–/R– transplants. These data support the recently published 2022 KDIGO guidelines on management of HCV in CKD, which strongly recommend consideration of hepatitis C-positive kidneys for all recipients irrespective of their serological status (10).
Although the results are promising, the authors caution about the lack of long-term data on the safety and graft survival in HCV D+/R– transplants. In this publication, HCV-positive kidneys were associated with 51% lower rates of delayed graft function compared with HCV D–/R–, and there was no difference in the acute rejection rates. It remains to be seen if this translates into a better long-term graft survival for HCV D+/R– transplants. Given these data, the cost of DAA therapy for HCV seems like a small price to pay for the savings gained by transitioning a patient off of dialysis to a functioning kidney allograft.
With the increase in kidney donors who are HCV positive, the transplant community will need to ensure that there is equal access to these organs. Prompt review of data and development of practice guidelines such as the KDIGO 2022 Hepatitis C Clinical Practice Guideline will facilitate education and adoption of these novel approaches by practitioners (10). Equally important are the goals of educating our patients and ensuring insurance coverage for the much-needed DAA therapies that cost more than $84,000 for a 12-week treatment (11). As noted by Gordon et al. (9), some patients did experience fibrosing cholestatic hepatitis when there was a delay in DAA therapy.
Since the gap between supply and need for kidneys remains large, it is imperative that innovative protocols are established to reduce kidney discards and optimize the long-term success of kidney transplants. Publication of the EXPANDER (5) and THINKER (4) trials in 2018 laid the foundation for transplantation of >7500 kidneys from donors who were HCV positive. The proportion of HCV-positive kidneys transplanted into recipients who are HCV negative has increased from 5% in 2015 to >90% in 2022 (Figure 1B). The systematic review by Gordon et al. (9) should further educate the transplant community and facilitate optimal utilization of the donor pool.
Footnotes
References
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Lentine KL, et al. OPTN/SRTR 2020 Annual Data Report: Kidney. Am J Transplant 2022; 22 (Suppl 2):21–136. doi: 10.1111/ajt.16982
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Burton JR Jr, et al. Liver and kidney recipient selection of hepatitis C virus viremic donors: Meeting consensus report from the 2019 controversies in transplantation. Transplantation 2020; 104:476–481. doi: 10.1097/TP.0000000000003014
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Nguyen VH, et al. Characteristics and treatment rate of patients with hepatitis C virus infection in the direct-acting antiviral era and during the COVID-19 pandemic in the United States. JAMA Netw Open 2022; 5:e2245424. doi: 10.1001/jamanetworkopen.2022.45424
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Durand CM, et al. The drug overdose epidemic and deceased-donor transplantation in the United States: A national registry study. Ann Intern Med 2018; 168:702–711. doi: 10.7326/M17-2451
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Levitsky J, et al. The American Society of Transplantation Consensus Conference on the Use of Hepatitis C Viremic Donors in Solid Organ Transplantation. Am J Transplant 2017; 17:2790–2802. doi: 10.1111/ajt.14381
- 9.↑
Gordon CE, et al. Kidney transplantation from hepatitis C virus-infected donors to uninfected recipients: A systematic review for the KDIGO 2022 hepatitis C clinical practice guideline update. Am J Kidney Dis (published online ahead of print April 14, 2023). doi: 10.1053/j.ajkd.2022.12.019; https://www.ajkd.org/article/S0272-6386(23)00592-9/fulltext
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Martin P, et al. Executive summary of the KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney Int 2022; 102:1228–1237. doi: 10.1016/j.kint.2022.07.012
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Henry B. Drug pricing & challenges to hepatitis C treatment access. J Health Biomed Law 2018; 14:265–283. PMID: 30258323
