Patient Willingness to Accept Hepatitis C-Infected Kidneys for Transplantation.

Background: As organs infected with Hepatitis C virus (HCV) provide an opportunity to expand the donor pool, the primary aim of this study is to gauge patient willingness to accept a kidney from HCV-infected donors compared to other high-risk donors. Methods: An anonymous, electronic survey was sent to all active kidney transplant waitlist patients at a single large volume transplant center. Patients were asked to respond to three hypothetical organ offers from the following: 1) HCV-infected donor 2) Donor with active intravenous drug use and 3) Donor with longstanding diabetes and hypertension. Results: The survey was sent to 435 patients of which 125 responded (29% response rate). While 86 out of 125 patients (69%) were willing to accept an HCV-infected kidney, only a minority of respondents were willing to accept a kidney from other high-risk donors. In contrast to other studies, by multivariable logistic regression, age and race were not associated with willingness to accept an HCV-infected kidney. Conclusions: From a patient perspective, utilization of kidneys from HCV-infected donors to expand the donor pool appears to be an acceptable option.


Background
There is a critical shortage of donor organs for patients awaiting kidney transplantation.According to the Organ Procurement and Transplantation Network (OPTN), nearly 100,000 patients remain on the kidney transplant waiting list in the United States (U.S.) and yet only 10,000 patients underwent deceased donor kidney transplantation in 2018.[1] As the demand for organs continues to outpace supply and waiting times exceed up to ve years in many parts of the country, multiple approaches are now being considered to safely expand the donor pool.[2] These include donation after circulatory death, public health service (PHS) increased risk donors, older donors with comorbidities, and those previously exposed to or infected with hepatitis C (HCV) .
The ongoing opioid epidemic in the U.S. has resulted in a dramatic increase in the number of deaths due to overdose with intravenous drug use (IVDU), leading to a signi cant increase in donors classi ed as PHS increased risk and those infected with HCV.[3] With the advent of direct-acting antiviral agents (DAA) for the treatment of HCV, there has been great interest in the potential to increase the donor pool by offering waitlisted patients HCV-infected kidneys.The cure rates of various DAA regimens exceed 90% in the general population and evidence is growing to suggest that similarly high cure rates can be achieved among immunosuppressed recipients and those with renal dysfunction.[4][5][6][7][8].Notably, two independent single-center pilot studies demonstrated 100% cure rates and excellent outcomes in a total of 30 uninfected patients who received HCV-infected kidneys and were subsequently treated with DAA posttransplant.[9,10].More recently, others have reported excellent outcomes on this practice when performed as standard of care, i.e. outside of a clinical trial.[11,12].
Despite the growing interest in the transplant community to broadly adopt the practice of transplanting HCV-infected kidneys into uninfected recipients, little is known about patient willingness to accept such kidneys and how this compares to willingness to accept other "non-standard" kidneys such as PHS increased risk and high kidney donor pro le index (KDPI).
The aims of this study were: First, to quantify patient willingness to receive a kidney from a donor with HCV-viremia; second, to compare this with willingness to accept a kidney from a representative PHS increased risk or marginal (high KDPI) donor; and third, to identify clinical characteristics associated with willingness to accept an HCV-infected kidney.

Participants and Survey Administration
An anonymous, electronic survey was administered to all active kidney transplant waitlist patients with a registered email address at a large volume transplant center in Nashville, TN as part of an exploratory initiative to gauge interest among waitlisted patients in accepting HCV-infected kidneys.As such, no pilot survey was conducted at the initiation of the study.However, all study materials were reviewed by transplant center staff who regularly produce educational and survey materials for this study population.
Multiple iterations were circulated among transplant center including surgery, nephrology, nursing, and administrative staff.Furthermore, the survey was set up in a similar fashion to the hypothetical situations posed by McCauley, et al, whose work was based on semi-structured interviews.[13] Survey data were collected via the REDCap electronic data capture tool.Patients were provided introductory information to the survey, including observed HCV cure rates with current DAA therapy, and were informed that participation was completely voluntary.All patients had previously undergone in-person pre-transplant education at the transplant center which included education regarding the risks and bene ts of PHSincreased risk and high KDPI kidneys, but not HCV-infected kidneys.This study was deemed exempt under the Institutional Review Board (IRB # 190290).

Demographic and Clinical Data
Patients were asked for demographic information (age, sex, race, ethnicity, education level), waitlist time, dialysis time, type of dialysis, and history of a prior kidney transplant.Patients were also asked if they had been diagnosed and/or treated for HCV and if they had any personal contacts with known history of HCV.They were then asked to respond to three hypothetical kidney offers as follows: 1) 20-year-old HCVinfected donor with a greater than 95% chance of successful HCV cure following transplant; 2) 20-yearold PHS-increased risk donor with active IVDU at time of death; and 3) 70-year-old donor with longstanding hypertension and diabetes.For those patients who reported "no" to any organ offer, they were then asked to indicate how much additional time they would be willing to remain on the transplant list in order to receive a "standard" kidney offer.Finally, patients were asked if added costs or doctor visits for HCV treatment were of concern to them.A full copy of the survey is included as Appendix A.

Statistical Analysis
This study was designed as an exploratory survey to gauge attitudes regarding willingness to accept HCV-positive organs and to shape further educational and outreach efforts regarding these organ offers.Thus, no sample size calculation was performed.Descriptive analysis including mean and median for continuous variables and frequencies for categorical variables were calculated.Student t test and oneway analysis of variance (continuous variables) and Fisher's exact test (categorical data) were used to compare differences between groups.Multivariable logistic regression was utilized to identify clinical characteristics which were independently associated with willingness to accept an HCV-infected kidney.
Covariates included in the model were chosen a priori and included age, race, gender, educational status, and time on dialysis.Time on dialysis was categorized to "less than 2 years" and "greater than or equal to 2 years" while educational status was categorized as "some college or less" and "graduated college, graduate or doctoral degree".All analyses were performed using Stata 15.1 (StataCorp, College Station, TX).

Results
A total of 435 patients who were actively listed for kidney transplant at our center and had a registered email address were sent the electronic link to the REDCap survey.There were 125 patients who responded (29% response rate).The demographic and clinical characteristics of the cohort are presented in Table 1.The mean age was 55 years, 57% were male, 66% were white, and 28% were black.Of the patients who responded, 70% are currently on dialysis, the majority of whom undergo hemodialysis (66%).Time on dialysis as well as time on transplant list (years) are also shown in Table 1.Out of 125 respondents, 86 (69%) were willing to accept an HCV-infected kidney.In unadjusted analysis, those patients willing to receive HCV-infected kidneys were signi cantly older (57 versus 51 years old, p=0.012).There was no signi cant difference in willingness to accept HCV-infected kidneys by sex, race, time on dialysis, or educational status (Table 1).In contrast to patient willingness to accept an HCVinfected kidney, only a minority of respondents were willing to accept a kidney from a donor with active IVDU at the time of death (37%) or from an older donor with long-standing history of diabetes and hypertension (39%) (Figure 1).
In multivariable logistic regression analysis, neither age (OR 1.03, 95% CI 0.99-1.07)nor race (OR 0.63, 95% CI 0.24-1.68)were signi cantly associated with willingness to accept HCV-infected kidneys after adjustment for sex, time on dialysis, or educational status.(Table 2).For those patients who reported "no" to any organ offer and were subsequently asked to respond to how much additional time they would be willing to wait in order to receive a "standard" kidney offer, those who declined an HCV-infected kidney were willing to wait for a mean additional time of 3.5 years.Finally, 38% of patients were concerned about the additional costs of HCV medications as well as the burden of additional o ce visits for HCV treatment.

Discussion
In a survey conducted in a large volume transplant center in the Southeastern United States, we found that most patients were willing to accept an offer for an HCV-infected kidney.In contrast to prior studies, our data demonstrate that there were no signi cant differences in willingness to accept offers for HCVinfected kidneys based on age and race.Our nding that majority of patients are interested in accepting an HCV-infected kidney is similar to what other groups who have found in their own patient population.However, in contrast to our ndings, these studies found that older patients and white patients were more willing to accept HCV-infected kidneys than younger and black patients, respectively.[13,14] The reason for the contrast in the results is unclear but may represent unmeasured differences in each transplant center's characteristics and patient population.
While our study demonstrates that many patients are open to HCV-infected kidneys once educated regarding the safety and e cacy of DAA therapy post-transplant, they also suggest that other types of "high-risk" donation is less clear to patients.The majority of our respondents were unwilling to receive an organ from a donor with active IVDU at the time of death, albeit with negative HIV and HCV serologies.
Similarly, the majority of our respondents were unwilling to receive an organ from an older donor with diabetes and hypertension, two disease states contributing to end-stage renal disease.In these scenarios, there may be an element of uncertainty regarding expected outcome for both the patient and the provider.
This lack of certainty is clearly problematic, as the designation of PHS-increased risk leads to nonutilization of hundreds of organs every year.
[15] In focus groups, Ros et al found that patients desired additional information about PHS-increased risk donors, including behaviors, kidney quality, and probability of undetected infection.This study also found that patients heavily weighed the opinion of their transplant provider in making recommendations regarding organ offers.[16] Participants in our survey received a modest amount of educational material regarding HCV-infected kidney offers and treatment prior to completing this anonymous survey.Given these data and other groups' ndings that patients prominently consider the opinion of the transplant provider in whether or not to accept an organ offer, we suggest that providers carefully consider the risks and bene ts of an organ offer with their patients.These discussions should include consideration of patient age, current quality of life, and ability to detect and treat potentially transmitted infections.
This study has several limitations.First, our response rate was low (29%), participation was voluntary, and the sample size was limited.Therefore, it is possible that our ndings are in uenced by non-response bias and that patients who are interested in HCV-infected kidneys would be more likely to respond to this survey.Second, all respondents are listed at a single academic institution, which may limit the generalizability of the study.Third, the survey was designed to primarily gauge interest in accepting HCVinfected kidneys, hence no additional education within the survey was provided regarding the risks and bene ts of accepting a PHS-increased risk or high KDPI kidney.However, patients did receive in-person education regarding these kidneys during their evaluation at our transplant center.Finally, due to the limited number of events and to avoid over tting the model, some other potential confounders may not have been included in the multivariable analysis.

Conclusions
Our data suggest that majority of patients currently on the waitlist for kidney transplant are willing to consider organ offers from HCV-infected kidneys, but less so from other "high-risk" donors.Compared to prior studies, we found no differences based on age and race.The contrast in results suggests a need for each transplant center to survey their own transplant population.Equipping patients and providers alike with more tools to navigate decision-making regarding higher-risk donors remains an area of ongoing research.

Table 1
Demographic and clinical characteristics of survey participants (n = 125).

Table 2
Multivariable logistic regression model for willingness to accept an HCV-infected kidney.