Resource Use and Financial Impact of Oral Step-Down Therapy for Resistant Cytomegalovirus in Solid Organ Transplant Recipients.

BACKGROUND: Cytomegalovirus (CMV) infections are common opportunistic infections in solid organ transplants (SOT) with increased health care resource USE and costs. Costs are further increased with ganciclovir-resistance (GR). This study aimed to evaluate the real-world impact of conversion to oral step-down therapy on duration of foscarnet and hospital length of stay (LOS) for treatment of GR-CMV infections in SOT. METHODS: This study included adult recipients of kidney or lung transplants who received foscarnet for genotypically documented GR-CMV while admitted at the University of Wisconsin Hospital from October 1, 2015, to January 31, 2022. Patients in the oral step-down group were converted from standard of care (SOC; foscarnet) to maribavir or letermovir; patients in the historical control group were treated with SOC. RESULTS: Twenty-six patients met the inclusion criteria: 5 in the intervention group and 21 in the SOC group. The median viral load at foscarnet initiation was 11,435 IU/mL. Patients who received oral step-down conversion had shorter mean foscarnet duration than those who received SOC (7 ± 4 vs 37 ± 25 days, P = .017). Mean hospital LOS in the oral step-down group (16 ± 3 days) was shorter than the SOC group (33 ± 21 days; P < .001). In the SOC group, 9 patients lost their graft, and 9 patients died; 2 deaths were attributed to CMV. There were 2 deaths in the oral step-down group, neither of which was attributed to CMV. CONCLUSION AND RELEVANCE: In this real-world case series of patients receiving treatment for GR-CMV infection, oral step-down conversion decreased foscarnet therapy duration and hospital LOS. Future studies are needed to evaluate better the effect of oral step-down in treating GR-CMV infection on treatment duration and cost-savings.

The clinical value of donor-derived cell-free DNA measurements in kidney transplantation.

Early diagnosis is critical to minimizing the damage rejection can do to the transplanted kidney. Donor-derived cell-free DNA (dd-cfDNA) represents non-encapsulated fragmented DNA that is continuously shed into the bloodstream from the allograft undergoing injury, with a half-life of about 30 min. This article reviews the available evidence regarding the diagnostic value of dd-cfDNA in kidney transplantation, as a result of which two assays, Allosure and Prospera, have garnered Medicare approval. We provide information on important scenarios and contexts including antibody-mediated rejection, T-cell mediated rejection, pre-test probability of rejection, timing of the test, repeat transplants, and background cell-free DNA levels to help our understanding of the test characteristics and utility of these assays in clinical practice. Data on multimodality assays including gene expression profiles and serial monitoring of dd-cfDNA in high risk situations are emerging.

Wages, Travel, and Lodging Reimbursement by the National Kidney Registry: An Important Step Toward Financial Neutrality for Living Kidney Donors in the United States.

BACKGROUND: Since 2007, the National Living Donor Assistance Center has provided the most financial support to US living donors meeting specific income criteria by reimbursing travel, meal, and lodging expenses. In 2019, the National Kidney Registry started providing lost wages, travel, and lodging reimbursement via their Donor Shield program. Donor Shield is automatically provided to donors who participate in kidney paired donation through the National Kidney Registry or who donate at a Donor Shield Direct center, without any income restrictions. METHODS: The support donors across the United States received from the Donor Shield program between January 2019 and February 2020 was studied. RESULTS: During the study period, 326 (25.9%) of the 1260 donors covered by Donor Shield, from 46 programs received reimbursements amounting to a total of $647 384.45, with $472 389.97 (73.0%) covering lost wages. Median reimbursement per donor was $1813.80 (range, $44.0-$165.63). Eighty-one percent of 108 reimbursed donors who were surveyed reported that the lack of these reimbursements would have posed a financial hardship, and 4% said they would have been unable to donate without this support. CONCLUSIONS: Expansion of lost wages reimbursement programs to all donors in the United States would be an important step toward achieving financial neutrality for this unique population and could also help meet the growing demand for transplantable organs by increasing living donation rates.

A Single-Center Assessment of Delayed Graft Function in Recipients of Simultaneous Liver and Kidney Transplant.

BACKGROUND: The effects of delayed graft function on long-term kidney allograft outcomes are poorly defined among simultaneous liver and kidney transplant recipients. METHODS: We analyzed data of all simultaneous liver and kidney recipients transplanted at the University of Wisconsin between 2010 and 2017. Risk factors for the development of delayed graft function, kidney graft failure, and patient mortality were outcomes of interest. RESULTS: There were a total of 60 simultaneous liver and kidney recipients; 28 (47%) had delayed graft function. After adjustment for multiple variables, we found that pretransplant dialysis >6 weeks (hazard ratio [HR] = 5.6, 95% CI: 1.23-25.59, P = .02), pretransplant albumin <3 g/dL (HR = 5.75, 95% CI: 1.76-16.94, P = .003), and presence of pretransplant diabetes (HR = 2.5, 95% CI: 0.97-4.77, P = .05) were significantly associated with delayed graft function. Multivariate analysis showed that pretransplant albumin <3 (HR = 4.86, 95% CI: 1.07-22.02, P = .02) was associated with a higher risk of all-cause kidney allograft failure, whereas the duration of delayed graft function (HR = 1.07 per day, 95% CI: 1.01-1.14, P = .01) was associated with a higher risk of death-censored kidney allograft failure. The presence of delayed graft function was not associated with all-cause or death-censored kidney or liver allograft failure. Similarly, the presence of delayed graft function was not associated with patient mortality. CONCLUSION: The incidence of delayed graft function was high in simultaneous liver and kidney recipients. However, with appropriate management, delayed graft function may not have a negative impact on patient or kidney allograft survival.

Use of Donor-Derived Cell-Free DNA for Assessment of Allograft Injury in Kidney Transplant Recipients During the Time of the Coronavirus Disease 2019 Pandemic.

BACKGROUND: Kidney allograft biopsy is the gold standard for diagnosis of rejection. Under the current extraordinary circumstances of the coronavirus disease 2019 (COVID-19), in which social distancing is key to limiting the spread of the virus, the model used to provide care to transplant recipients has undergone a very rapid transformation. In the spirit of medical distancing, we have been using the donor-derived cell-free DNA (dd-cfDNA) test for screening for rejection. METHODS: This article describes our experience with this approach between March 15th and May 20th, 2020. RESULTS: This test was obtained for-cause in 23 patients and for monitoring in 9 patients. Normal results aided in forgoing biopsy in 63% of the patients for whom the test was obtained in the outpatient setting. The test is neither 100% sensitive nor specific for rejection; however, when used in combination with the available clinical information, it can be used for determining whether bringing in a transplant recipient into a medical facility is necessary. CONCLUSIONS: In the event COVID-19 becomes a long-term challenge for our community, noninvasive biomarkers such as the dd-cfDNA may become more relevant than ever in enhancing our ability to care for our transplant patients while maximizing the distancing measures.

Epidemiology, management, and graft outcomes after West Nile virus encephalitis in kidney transplant recipients.

BACKGROUND: Minimal data exist describing the epidemiology, management, and long-term graft outcomes after West Nile viral disease in kidney transplant recipients (KTRs). METHODS: Single-center observational cohort study of patients who received a kidney transplant between 1/1/1994 and 12/31/2018 and developed WNV at any time point after transplantation. RESULTS: During the 24-year study period, 11 patients had documented WNV infection. Seven patients were recipients of a kidney transplant alone, and four had a simultaneous kidney and pancreas transplant. The mean age at the time of transplant was 44.7 ± 17.1 years, and the mean age at the time of WNV infection was 48 ± 17.2 years. All patients received lymphocyte depleting induction at transplant (alemtuzumab (n = 2), OKT3 (n = 1), or anti-thymocyte globulin (n = 8)). The mean time from transplant to WNV infection was 3.4 ± 5.4 years, and none was suspected of having a donor-derived infection. Three patients were treated for rejection in the 6 months before infection. The most common presenting symptom was altered mental status (n = 7), followed by a combination of fever and headache (n = 4). All patients had detectable serum WNV IgM antibodies at the time of diagnosis. All patients had a reduction in their immunosuppression and received supportive care; only two patients were treated with intravenous immunoglobulins. Nine patients recovered with no residual deficit; however, two suffered permanent neurologic damage. The mean estimated glomerular filtration rate drop at 1 year after the infection was 8.4 ± 13 mL/min/1.73 m2 . Three patients suffered acute rejection within 1 year after the infection episode, likely attributable to aggressive immunosuppressive reduction. The mean follow-up after the infection was 5.1 ± 4.3 years. At last follow-up, two patients lost their kidney allograft, and five patients died. None of the graft losses or deaths occurred within a year of the WNV or were directly attributable to WNV. CONCLUSION: The majority of patients with WNV infection after KTR recovered fully with supportive care and immunosuppressive adjustment without residual neurologic sequelae. Additionally, WNV infection was associated with relatively small reductions in eGFR at 1 year.

Outcomes in the highest panel reactive antibody recipients of deceased donor kidneys under the new kidney allocation system.

Since the institution of the new kidney allocation system in December 2014, kidney transplant candidates with the highest calculated panel reactive antibodies (cPRA) of 99-100 have been transplanted at much higher rates. However, concerns have been raised that outcomes in these patients might be impaired due to higher immunological risk and longer cold ischemia times resulting from long-distance sharing of kidneys. Here, we compare outcomes at the University of Wisconsin between study patients with cPRA 99-100 and all other recipients of deceased donor kidneys transplanted between 12/04/2014 and 12/31/2015. All patients had at least 6 months post-transplant follow-up. The mean follow-up was 13.9±3 months in cPRA ≥99% and 12.3±3.5 months in cPRA ≤98%. There was a total of 152 transplants, 25 study patients, and 127 controls. No statistically significant differences were found between the two groups in delayed graft function, rejection, kidney function, graft and patient survival, or infections. We conclude that transplanting the most highly sensitized patients with kidneys shared outside their local donation service areas is associated with excellent short-term outcomes that are comparable to controls.

Barriers to the use of a federal travel grant by living kidney donors.

Living organ donation involves significant out-of-pocket costs, which burden donor candidates and may be an obstacle to donation. There is a single US grant (the National Living Donor Assistance Center-NLDAC) to cover live donor travel costs. Although there may be center-specific variability in grant utilization, prospective donors-and their intended recipients-must also meet eligibility criteria. In fact, the NLDAC grant is used by <10% of US live donors annually. We studied 154 consecutive kidney donor clinic evaluations (November 1, 2014-August 30, 2015) to determine eligibility and usage patterns during the evaluation process. Of these, 63 (41%) were local, had travel benefits, or declined. Of the remaining 91 prospective donors who might have benefited from grant support, only 29 (32%) obtained the grant. The other 62 (68%) did not meet eligibility screening. The major reason prospective donors were ineligible was that the recipient's household income was outside the required means test (ie, >300% of the federal poverty level) (n=51; 82%). The remaining exclusions (n=11; 18%) included being a nondirected donor, not meeting residency requirements, and "other." Expanding NLDAC eligibility criteria-by broadening the recipient means test or by taking steps to eliminate it from the NLDAC charter-would reduce financial burdens associated with live donation.

Concern for Lost Income Following Donation Deters Some Patients From Talking to Potential Living Donors.

CONTEXT: Some living kidney donors report lost income during recovery from surgery. Little is known about whether concern for living donor's lost income affects the decision to undergo donation evaluation and the willingness of transplant candidates to discuss living kidney donation (LKD) with others. OBJECTIVE: To examine whether transplant patients were told by potential donors about lost income concerns and whether patients chose not to discuss LKD with others due to lost income concerns. DESIGN, SETTING, AND PATIENTS: Kidney transplant patients (185 wait-listed candidates, 171 deceased donor recipients, and 100 live donor recipients) at 2 centers completed a questionnaire to assess whether concern about donor's lost income was a consideration in discussion about LKD with others. RESULTS: One-third (32%) were told by a family member/friend that they were willing to donate but were concerned about potential lost income. The majority of those who expressed financial concern (64%) did not initiate donation evaluation. Many patients (42%) chose not to discuss living donation with a family member/friend due to concern about the impact of lost income on the donor. In the multivariable model, lower annual household income was the only statistically significant predictor of both having a potential donor expressing lost income concern and choosing not to talk to someone because of lost income concern. CONCLUSION: Findings from the current study underscore how concern about income loss for living donors may affect decision-making by both transplant candidates and potential donors.

Living Donor Kidney Transplantation: Overcoming Disparities in Live Kidney Donation in the US--Recommendations from a Consensus Conference.

Despite its superior outcomes relative to chronic dialysis and deceased donor kidney transplantation, live donor kidney transplantation (LDKT) is less likely to occur in minorities, older adults, and poor patients than in those who are white, younger, and have higher household income. In addition, there is considerable geographic variability in LDKT rates. Concomitantly, in recent years, the rate of living kidney donation (LKD) has stopped increasing and is declining, after decades of consistent growth. Particularly noteworthy is the decline in LKD among black, younger, male, and lower-income adults. The Live Donor Community of Practice within the American Society of Transplantation, with financial support from 10 other organizations, held a Consensus Conference on Best Practices in Live Kidney Donation in June 2014. The purpose of this meeting was to identify LKD best practices and knowledge gaps that might influence LDKT, with a focus on patient and donor education, evaluation efficiencies, disparities, and systemic barriers to LKD. In this article, we discuss trends in LDKT/LKD and emerging novel strategies for attenuating disparities, and we offer specific recommendations for future clinical practice, education, research, and policy from the Consensus Conference Workgroup focused on disparities.

Concerns of ABO incompatible and crossmatch-positive potential donors and recipients about participating in kidney exchanges.

Kidney paired exchanges (KPEs) have increased, yet are still underutilized. This study aimed to develop tools for assessing KPE concerns, identify predictors of KPE concerns, and describe common KPE concerns among potential living donors (LDs) and intended recipients. Incompatible former potential LDs (n = 135) and intended recipients (n = 83) retrospectively completed questionnaires to assess KPE concerns. Healthcare system distrust also was assessed. A minority (n = 48 or 36.5% of potential LDs; n = 25 or 30.1% of intended recipients) had pursued KPE participation. Of those who pursued KPE participation, 11 (22.9%) and 6 (24.0%) completed KPE donation or transplantation, respectively. The questionnaires for potential LDs and recipients showed good internal consistency and preliminary convergent validity. LDs and patients less willing to pursue KPE reported more KPE concerns. Common KPE concerns for both potential LDs and recipients were related to perceived Distrust/Inequity and Inconvenience/Cost. Multivariate predictors of more KPE concerns were as follows: male gender (t = 4.5, p < 0.001) and more healthcare system distrust (t = 2.5, p = 0.01) for potential LDs; black race (t = 2.1, p = 0.04) and more healthcare system distrust (t = 2.3, p = 0.03) for intended recipients. These findings underscore the importance of addressing concerns potential LDs and patients have about KPE if the true potential of KPE is to be realized.

The decline in living kidney donation in the United States: random variation or cause for concern?

The annual number of living kidney donors in the United States peaked at 6647 in 2004. The preceding decade saw a 120% increase in living kidney donation. However, since 2004, living kidney donation has declined in all but 1 year, resulting in a 13% decline in the annual number of living kidney donors from 2004 to 2011. The proportional decline in living kidney donation has been more pronounced among men, blacks, younger adults, siblings, and parents. In this article, we explore several possible explanations for the decline in living kidney donation, including an increase in medical unsuitability, an aging transplant patient population, financial disincentives, public policies, and shifting practice patterns, among others. We conclude that the decline in living donation is not merely reflective of random variation but one that warrants action by the transplant centers, the broader transplant community, and the state and national governments.

Reimbursement for living kidney donor follow-up care: how often does donor insurance pay?

BACKGROUND: Currently, many transplantation centers do not follow former living kidney donors on a long-term basis. Several potential barriers have been identified to provide this follow-up of former living kidney donors, including concerns that donor insurance will not reimburse transplantation centers or primary care physicians for this care. Here, we report the rates at which different insurance companies reimbursed our transplantation center for follow-up visits of living donors. METHODS: We collected data on all yearly follow-up visits of living donors billed from January 1, 2007, to December 31, 2010, representing 82 different donors. Concurrent visits of their recipients were available for 47 recipients and were used as a control group. RESULTS: We find that most bills for follow-up visits of living kidney donors were paid by insurance companies, at a rate similar to the reimbursement for recipient follow-up care. CONCLUSIONS: Our findings suggest that, for former donors with insurance, inadequate reimbursement should not be a barrier in providing follow-up care.

Liver transplant center risk tolerance.

Recent changes in Center for Medicare & Medicaid Services (CMS) condition for participation, using benchmark volume/outcomes requirements for certification, have been implemented. Consequently, the ability of a transplant center to assess its risk tolerance is important in successful management. An analysis of SRTR data was performed to determine donor/recipient risk factors for graft loss or patient death in the first year. Each transplant performed was then assigned a prospective relative risk (RR) of failure. Using a Monte-Carlo simulation, transplants were selected at random that met the centers' acceptable risk tolerance. Transplant center volume was fixed and its risk tolerance was adjusted to determine the impact on outcomes. The model was run 1000 times on centers with varying volume. The modeling demonstrates that centers with smaller annual volumes must use a more risk taking strategy than larger volume centers to avoid being flagged for CMS volume requirements. The modeling also demonstrates optimal risk taking strategies for centers based upon volume to minimize the probability of being flagged for not meeting volume or outcomes benchmarks. Small volume centers must perform higher risk transplants to meet current CMS requirements and are at risk for adverse action secondary to chance alone.

The "House Calls" trial: a randomized controlled trial to reduce racial disparities in live donor kidney transplantation: rationale and design.

Despite a substantially lower rate of live donor kidney transplantation among Black Americans compared to White Americans, there are few systematic efforts to reduce this racial disparity. This paper describes the rationale and design of a randomized controlled trial evaluating the comparative effectiveness of three different educational interventions for increasing live donor kidney transplantation in Black Americans. This trial is a single-site, urn-randomized controlled trial with a planned enrollment of 180 Black Americans awaiting kidney transplantation. Patients are randomized to receive transplant education in one of three education conditions: through group education at their homes (e.g., House Calls), or through group (Group-Based) or individual education (Individual Counseling) in the transplant center. The primary outcome of the trial is the occurrence of a live donor kidney transplant, with secondary outcomes including living donor inquiries and evaluations as well as changes in patient live donor kidney transplantation readiness, willingness, knowledge, and concerns. Sex, age, dialysis status, and quality of life are evaluated as moderating factors. Findings from this clinical trial have the potential to inform strategies for reducing racial disparities in live donor kidney transplantation. Similar trials have been developed recently to broaden the evaluation of House Calls as an innovative disparity-reducing intervention in kidney transplantation.

Spouse caregivers of kidney transplant patients: quality of life and psychosocial outcomes.

CONTEXT: Most kidney transplant programs require patients to identify a primary caregiver who can assist them throughout the transplant process. Little is known about the quality of life, caregiving strain, and psychosocial functioning of these caregivers. OBJECTIVES: To characterize the psychosocial functioning of spouse/partner caregivers. DESIGN, SETTINGS, AND PARTICIPANTS: Cross-sectional survey administered to spouse/partner caregivers of patients before (n=33) and after (n=46) kidney transplantation at a transplant center in New England. MAIN OUTCOME MEASURES: Quality of life, life satisfaction, caregiving strain and benefit, mood, and social intimacy. RESULTS: Relative to normative samples and published data involving other transplant caregivers, caregivers of kidney transplant patients had favorable quality of life, life satisfaction, psychological, and social intimacy outcomes. Life satisfaction scores were significantly lower for caregivers before than after kidney transplantation, but otherwise the 2 cohorts did not differ significantly from each other. Most caregivers both before and after kidney transplantation reported clinically high levels of caregiving strain, as well as several caregiving benefits. CONCLUSION: Our data are consistent with results of other studies in showing that spouses experience considerable caregiving strain both before and after transplantation. However, caregivers of kidney transplant patients overall have good quality of life, life satisfaction, mood, and social intimacy. More prospective research is necessary to characterize better how these outcomes change over time throughout the transplant process.

Measuring the expectations of kidney donors: initial psychometric properties of the Living Donation Expectancies Questionnaire.

We report on the initial development and validation of the Living Donation Expectancies Questionnaire (LDEQ), designed to measure the expectations of living kidney donor candidates. Potential living donors (n=443) at two transplant centers were administered the LDEQ and other questionnaires, and their medical records were reviewed. Factor analysis provides support for six LDEQ scales: Interpersonal Benefit, Personal Growth, Spiritual Growth, Quid Pro Quo, Health Consequences, and Miscellaneous Consequences. All but one scale showed good internal consistency. Expected benefits of donation were associated with higher optimism and lower mental health; expected consequences of donation were associated with lower optimism and lower physical and mental health. More potential donors with relative or absolute contraindications had high Interpersonal Benefit (P<0.0001), Personal Growth (P<0.01), Quid Pro Quo (P<0.0001), and Health Consequences (P<0.0001) expectations. The LDEQ has promise in evaluating donor candidates' expectations.