Optimizing Utilization of Kidneys from Hepatitis C–Positive Kidney Donors

Kidney transplantation is the preferred treatment for kidney failure. Despite significant mismatch in supply and demand, about one out of five kidneys (22.6% in 2018) recovered for transplantation are discarded in the United States. Positive viremic status for hepatitis C virus (HCV) is still a significant cause for discard, and HCV prevalence among deceased donors is on the rise during the opioid epidemic. The Organ Procurement and Transplant Network (OPTN) amended their policy, and the organ procurement organizations were mandated to perform HCV nucleic acid testing (NAT) for all deceased donors in addition to HCV antibody serology on March 31, 2015. The introduction of direct-acting antivirals (DAAs) has revolutionized the treatment of HCV infection since 2014, and they have been increasingly used with very high success in patients with CKD and kidney transplantation. Therefore, DAAs have allowed utilization of HCV-viremic donors into HCV-naïve kidney transplant candidates (1,2), which was historically limited to only HCV-seropositive patients. Furthermore, several studies have now described the cost-effectiveness of DAA treatment in HCV-naïve recipients after receiving viremic donor kidneys, and encouragingly short-duration treatments are becoming increasingly effective (3).

In this issue of CJASN, Alhamad et al. (4) examine the trend of deceased donor kidney discards on the basis of HCV antibody and NAT status in the United States between January 1, 2005 and September 30, 2019 using a national registry collected by OPTN. In the first analysis, the authors reported an HCV seropositivity rate of 5% among recovered kidneys (n=225,479) during the study period (2005–2019) and an approximately six-fold decrease in the odds of discard between 2014 and 2019 among HCV-seropositive kidneys compared with seronegative ones. In the second analysis (2015–2019), of 82,090 deceased donor kidneys recovered, the authors reported 4% of the kidneys originated from viremic donors and 2% originated from aviremic seropositive donors. Compared with aviremic seronegative kidneys, the odds of discard in viremic kidneys significantly decreased from adjusted odds ratio of 4.89 (95% confidence interval, 4.03 to 5.92) in 2018 to adjusted odds ratio of 1.48 (95% confidence interval, 1.22 to 1.81) in 2019 (unadjusted discard rates declining from 39% in 2018 to 26% in 2019). On the contrary, compared with aviremic seronegative kidneys, aviremic seropositive kidneys did not have higher discard odds in 2019. The authors showed a wide variation in the discard rates of HCV-viremic kidneys among the United Network of Organ Sharing (UNOS) regions (the lowest in UNOS Region 1 [26%] versus the highest in UNOS Region 5 [50%]) between 2015 and 2019. Not surprisingly (5), viremic donor kidney recipients had a higher eGFR at 1 year compared with propensity-matched aviremic seronegative kidneys, regardless of their kidney donor profile index (KDPI) category (KDPI 50%–85% or 85%–100%).

This contemporary analysis utilized data from a large national registry and a multilevel multivariable logistic regression model (adjusted for 11 donor characteristics), assessing the association of HCV status with discard and accounting for discard patterns within organ procurement organization clusters and the UNOS regions. The authors advocate for broader utilization of HCV-viremic kidneys in HCV-naïve waitlisted candidates. As a result, they expect to see a constant decline in viremic discard similar to the aviremic seronegative kidney trajectory. They also promote a modified version of the KDPI calculation either excluding or adjusting the β-coefficient of HCV in the formula to highlight new lower risk with HCV viremic donor status in the presence of effective DAAs, comparable short-term allograft, and patient survival, and noninferior eGFRs at 1 year (knowing eGFRs are not necessarily predicted by KDPI percentile) compared with propensity-matched seronegative aviremic donor kidney recipients.

There has been a persistent increase in the acceptance and utilization of viremic kidneys in HCV-naïve recipients among transplant centers in the past 4 years. Earlier, we had predicted a continued rise in HCV-viremic donors (6), and the authors show such an increase (from 596 in 2015 to 1291 in the first 9 months of 2019) over the study period in the second analysis. With such an increase, HCV-viremic donors’ contribution to the kidney pool increased from 3.5% in 2015 to 6.5% in 2019. We believe that, if this analysis was performed with the most current OPTN data (September 2020), it would be reasonable to expect the odds of viremic kidney discard to be similar to aviremic seronegative kidneys, despite postcoronavirus disease 2019 era unpredictabilities. Notwithstanding the large sample size of this analysis, the OPTN data lack granularity regarding donor viral genotype and load, post-transplant DAA therapy (timing, duration, efficacy, and side effects), recipient selection, and hepatic complications related to DAA resistance. These are some of the essential data waiting to be collected nationally to advise the broader utilization of viremic donors in naïve recipients (7,8).

KDPI (a cumulative percentage scale of the kidney donor risk index score) is a critical component of the new kidney allocation system that estimates the likelihood of post-transplant allograft failure associated with ten deceased donor characteristics using kidney transplants performed between 1995 and 2005 in the United States (9). Donor HCV serology is one of the components in the KDPI calculation, and a positive serology could increase the KDPI percentile by 20% (suggesting shorter longevity of allograft) for the same donor characteristics with HCV-negative serology (10). However, compared with the implication of HCV serology status (practically, consequences of transplanting a seropositive aviremic kidney similar to seronegative aviremic kidney), deceased donor HCV NAT status (viremic versus aviremic) is more critical information to know in terms of disease transmission, post-transplant outcomes, and need for DAA treatment. We agree with the authors that a modified KDPI formula would be more appropriate soon on the basis of a Cox regression using HCV NAT status in a contemporary cohort transplanted after 2015.

One of the questions related to the broader utilization of HCV-viremic kidneys is how to allocate them optimally. Traditionally, HCV-seropositive kidneys were offered to waitlisted candidates with prior HCV infection, which made sense economically due to the high cost of DAA treatment ($40,000–$50,000 for a 2- to 3-month course). However, willingness to accept and the number of transplants from HCV-viremic kidneys to HCV-seronegative waitlisted candidates have outperformed the former approach. For example, in 2019, of 1105 kidneys transplanted from HCV-viremic donors, 81.1% (n=896) of kidneys were allocated to HCV-seronegative recipients, whereas 77% of HCV-seropositive recipients (n=602) received HCV NAT-negative kidneys (B. Tanriover, unpublished data; on the basis of our analysis of the UNOS Standard Transplant Analysis Research file). It would be interesting to look at the effect of this drastic change on HCV-seropositive candidates’ time spent on the waiting list and the decision regarding the optimal timing of DAA treatment (pre- versus post-transplant). Because of the limitations in OPTN’s data collection (candidates’ antibody serologies and NAT status are not reported at listing), it is currently difficult to predict the estimated time to transplant for candidates with HCV seropositivity.

This study newly addresses a wide regional difference in utilization of viremic kidneys, suggesting geographic variation in demand (the acceptance by transplant centers) and supply (the evolving opioid epidemic since 2000). In 2019, of 1443 viremic kidneys recovered for kidney transplantation, 76.4% were transplanted (locally 31.3% and shared 45.1%), and 23.6% were discarded (locally 19.3% and shared 4.3%), showing a higher risk of discard when the viremic kidneys were allocated locally in the OPTN regions not typically utilizing such kidneys (B. Tanriover, unpublished data; on the basis of our analysis of the UNOS Standard Transplant Analysis Research file). A more thought-provoking issue concerning HCV-viremic kidney utilization is the upcoming kidney-pancreas allocation changes (removal of the donor service areas and OPTN regions to decrease geographic disparities in access to transplantation; expected to be implemented on February 13, 2021). In the new system, deceased donor kidney and pancreas will initially be allocated to candidates waitlisted at transplant centers within 250 nautical miles of the donor hospital, except the candidates with 100% sensitization. It will be challenging to estimate future viremic kidney utilization due to the disruption caused by the coronavirus disease 2019 pandemic and new allocation changes prioritizing the inside circle kidney distribution.

To improve HCV-viremic kidney utilization and guide optimal allocation among waitlisted candidates with or without HCV NAT positivity, the transplant community needs a coordinated approach, including (1) expanding the OPTN data collection on donor characteristics (viral genotype and load), recipient characteristics (HCV serology and NAT status/genotype at listing), post-transplant DAA therapy (timing, duration, efficacy, and side effects), and hepatic complications related to DAA resistance; (2) launching government-funded multicenter studies; (3) granting uniform, timely access to DAAs and eliminating insurance coverage hurdles; (4) instituting evidence-based guidelines regarding transplant options; (5) disseminating web-based teaching tools to educate patients; and (6) establishing institutional multidisciplinary expert provider evaluation and follow-up.

Disclosures

V.K. Ariyamuthu reports employment with Banner University Medical Center/University of Arizona; receiving honoraria from CareDx, Natera, and Veloxis; and serving as a scientific advisor or member of the National Kidney Foundation Scientific Advisory Board. B. Tanriover reports employment with the University of Arizona, College of Medicine (Tucson, AZ); invitation for the advisory board meeting of CareDx in 2020; and serving on the Kidney International Reports Editorial Board.

Funding

None.