Expanding the access to kidney transplantation: Strategies for kidney transplant programs.

Kidney transplantation is the most successful kidney replacement therapy available, resulting in improved recipient survival and societal cost savings. Yet, nearly 70 years after the first successful kidney transplant, there are still numerous barriers and untapped opportunities that constrain the access to transplant. The literature describing these barriers is extensive, but the practices and processes to solve them are less clear. Solutions must be multidisciplinary and be the product of strong partnerships among patients, their networks, health care providers, and transplant programs. Transparency in the referral, evaluation, and listing process as well as organ selection are paramount to build such partnerships. Providing early culturally congruent and patient-centered education as well as maximizing the use of local resources to facilitate the transplant work up should be prioritized. Every opportunity to facilitate pre-emptive kidney transplantation and living donation must be taken. Promoting the use of telemedicine and kidney paired donation as standards of care can positively impact the work up completion and maximize the chances of a living donor kidney transplant.

Use of LCP-Tacrolimus (LCPT) in Kidney Transplantation: A Delphi Consensus Survey of Expert Clinicians.

BACKGROUND LCPT (Envarsus XR®) is a common once-daily, extended-release oral tacrolimus formulation used in kidney transplantation. However, there are minimal evidence-based recommendations regarding optimal dosing and treatment in the de novo and conversion settings. MATERIAL AND METHODS Using Delphi methodology, 12 kidney transplantation experts with LCPT experience reviewed available data to determine potential consensus topics. Key statements regarding LCPT use were generated and disseminated to the panel in an online Delphi survey. Statements were either accepted, revised, or rejected based on the level of consensus, perceived strength of evidence, and alignment with clinical practice. Consensus was defined a priori as ≥75% agreement. RESULTS Twenty-three statements were generated: 14 focused on de novo LCPT use and 9 on general administration or LCPT conversion use. After 2 rounds, consensus was achieved for 11/14 of the former and 7/9 of the latter statements. In a de novo setting, LCPT was recognized as a first-line option based on its safety and efficacy compared to immediate-release tacrolimus. In particular, African Americans and rapid metabolizer populations were identified as preferred for first-line LCPT therapy. In a conversion setting, full consensus was achieved for converting to LCPT to address neurological adverse effects related to immediate-release tacrolimus and for the time required (approximately 7 days) for steady-state LCPT trough levels to be reached. CONCLUSIONS When randomized clinical trials do not replicate current utilization patterns, the Delphi process can successfully generate consensus statements by expert clinicians to inform clinical decision-making for the use of LCPT in kidney transplant recipients.

Should Transplant Nephrology Pursue Recognition from the Accreditation Council for Graduate Medical Education (ACGME)?

Kidney transplant is not only the best treatment for patients with advanced kidney disease but it also reduces health care expenditure. The management of transplant patients is complex as they require special care by transplant nephrologists who have expertise in assessing transplant candidates, understand immunology and organ rejection, have familiarity with perioperative complications, and have the ability to manage the long-term effects of chronic immunosuppression. This skill set at the intersection of multiple disciplines necessitates additional training in Transplant Nephrology. Currently, there are more than 250,000 patients with a functioning kidney allograft and over 100,000 waitlisted patients awaiting kidney transplant, with a burgeoning number added to the kidney transplant wait list every year. In 2022, more than 40,000 patients were added to the kidney wait list and more than 25,000 received a kidney transplant. The Advancing American Kidney Health Initiative, passed in 2019, is aiming to double the number of kidney transplants by 2030 creating a need for additional transplant nephrologists to help care for them. Over the past decade, there has been a decline in the Nephrology-as well Transplant Nephrology-workforce due to a multitude of reasons. The American Society of Transplantation Kidney Pancreas Community of Practice created a workgroup to discuss the Transplant Nephrology workforce shortage. In this article, we discuss the scope of the problem and how the Accreditation Council for Graduate Medical Education recognition of Transplant Nephrology Fellowship could at least partly mitigate the Transplant Nephrology work force crisis.

Kidney Transplant Clinicians' Perceptions of Palliative Care for Patients With Failing Allografts in the US: A Mixed Methods Study.

RATIONALE & OBJECTIVE: Kidney transplant patients with failing allografts have a physical and psychological symptom burden as well as high morbidity and mortality. Palliative care is underutilized in this vulnerable population. We described kidney transplant clinicians' perceptions of palliative care to delineate their perceived barriers to and facilitators of providing palliative care to this population. STUDY DESIGN: National explanatory sequential mixed methods study including an online survey and semistructured interviews. SETTING & PARTICIPANTS: Kidney transplant clinicians in the United States surveyed and interviewed from October 2021 to March 2022. ANALYTICAL APPROACH: Descriptive summary of survey responses, thematic analysis of qualitative interviews, and mixed methods integration of data. RESULTS: A total of 149 clinicians completed the survey, and 19 completed the subsequent interviews. Over 90% of respondents agreed that palliative care can be helpful for patients with a failing kidney allograft. However, 46% of respondents disagreed that all patients with failing allografts benefit from palliative care, and two-thirds thought that patients would not want serious illness conversations. More than 90% of clinicians expressed concern that transplant patients and caregivers would feel scared or anxious if offered palliative care. The interviews identified three main themes: (1) transplant clinicians' unique sense of personal and professional responsibility was a barrier to palliative care engagement, (2) clinicians' uncertainty regarding the timing of palliative care collaboration would lead to delayed referral, and (3) clinicians felt challenged by factors related to patients' cultural backgrounds and identities, such as language differences. Many comments reflected an unfamiliarity with the broad scope of palliative care beyond end-of-life care. LIMITATIONS: Potential selection bias. CONCLUSIONS: Our study suggests that multiple barriers related to patients, clinicians, health systems, and health policies may pose challenges to the delivery of palliative care for patients with failing kidney transplants. This study illustrates the urgent need for ongoing efforts to optimize palliative care delivery models dedicated to kidney transplant patients, their families, and the clinicians who serve them. PLAIN-LANGUAGE SUMMARY: Kidney transplant patients experience physical and psychological suffering in the context of their illnesses that may be amenable to palliative care. However, palliative care is often underutilized in this population. In this mixed-methods study, we surveyed 149 clinicians across the United States, and 19 of them completed semistructured interviews. Our study results demonstrate that several patient, clinician, system, and policy factors need to be addressed to improve palliative care delivery to this vulnerable population.

Medical and Surgical Management of the Failed Pancreas Transplant.

Despite the continued improvements in pancreas transplant outcomes in recent decades, a subset of recipients experience graft failure and can experience substantial morbidity and mortality. Here, we summarize what is known about the failed pancreas allograft and what factors are important for consideration of retransplantation. The current definition of pancreas allograft failure and its challenges for the transplant community are explored. The impacts of a failed pancreas allograft are presented, including patient survival and resultant morbidities. The signs, symptoms, and medical and surgical management of a failed pancreas allograft are described, whereas the options and consequences of immunosuppression withdrawal are reviewed. Medical and surgical factors necessary for successful retransplant candidacy are detailed with emphasis on how well-selected patients may achieve excellent retransplant outcomes. To achieve substantial medical mitigation and even pancreas retransplantation, patients with a failed pancreas allograft warrant special attention to their residual renal, cardiovascular, and pulmonary function. Future studies of the failed pancreas allograft will require improved reporting of graft failure from transplant centers and continued investigation from experienced centers.

Twelve-month kidney and liver outcomes of kidney transplantation from Hepatitis C Viremic deceased donors to aviremic recipients.

INTRODUCTION: Utilization of hepatitis C viremic (HCV+) deceased donor kidneys (DDKT) for aviremic recipients increases opportunities for transplantation with excellent short-term outcomes. Our primary aim was to understand longer-term outcomes, specifically assessing kidney and liver function in the first year posttransplant. METHODS: This was a retrospective single-center study of adult DDKT recipients of HCV+ kidneys (cases) matched 1:1 to recipients of HCV- kidneys (comparators). Between-group outcomes were analyzed using comparisons of means and proportions, survival analysis methods, and multivariable mixed effects models. RESULTS: Sixty-five cases and 65 comparators had statistically comparable demographic and clinical characteristics. There were no between-group differences in serum creatinine or estimated glomerular filtration rate at month 12 (p = .662) or in their trajectories over months 1-12 (p > .292). Within the first 60 days, rates of liver function values >3 times upper limit of normal among cases were comparable to comparators for aspartate aminotransferase (AST) (14% vs. 6%, p = .242) and higher for alanine transaminase (ALT) (23% vs. 6%, p = .011). AST declined during the first 8 weeks (p = .005) and stabilized for both groups (p = .406) during the following 10 months. ALT declined during the first 8 weeks (p < .001), continued to decline over months 3-12 (p = .016), and the trajectory was unrelated to antiviral therapy initiation among cases. CONCLUSIONS: Aviremic recipients of HCV+ kidneys had comparable kidney outcomes to matched recipients of HCV- kidneys. Despite more HCV+ recipients having an elevation in ALT within the first 60 days, ALT values normalized with no identified liver complications attributed to HCV.

Prospective observational study to validate a next-generation sequencing blood RNA signature to predict early kidney transplant rejection.

The objective of this study was to validate the performance of Tutivia, a peripheral blood gene expression signature, in predicting early acute rejection (AR) post-kidney transplant. Recipients of living or deceased donor kidney transplants were enrolled in a nonrandomized, prospective, global, and observational study (NCT04727788). The main outcome was validation of the area under the curve (AUC) of Tutivia vs serum creatinine at biopsy alone, or Tutivia + serum creatinine at biopsy. Of the 151 kidney transplant recipients, the mean cohort age was 53 years old, and 64% were male. There were 71% (107/151) surveillance/protocol biopsies and 29% (44/151) for-cause biopsies, with a 31% (47/151) overall rejection rate. Tutivia (AUC 0.69 [95% CI: 0.59-0.77]) and AUC of Tutivia + creatinine at biopsy (0.68 [95% CI: 0.59-0.77]) were greater than the AUC of creatinine at biopsy alone (0.51.4 [95% CI: 0.43-0.60]). Applying a model cut-off of 50 (scale 0-100) generated a high- and low-risk category for AR with a negative predictive value of 0.79 (95% CI: 0.71-0.86), a positive predictive value of 0.60 (95% CI: 0.45-0.74), and an odds ratio of 5.74 (95% CI: 2.63-12.54). Tutivia represents a validated noninvasive approach for clinicians to accurately predict early AR, beyond the current standard of care.

Chronic Kidney Disease After Liver Transplantation.

Chronic kidney disease among liver transplant recipients is common and associated with an increased mortality risk. Several risk factors and causes for the development of chronic kidney disease have been identified. They can be divided into perioperative factors, such as unresolved acute kidney injury; donor-related factors, such as the use of extended criteria liver allografts; and recipient-related factors, such as the use of calcineurin inhibitors and the presence of metabolic syndrome, diabetes, and obesity. There is a bimodal progression, more prominent during the initial post-transplant months, followed by a gradual but progressive decline over the subsequent years. Management strategies to prevent and treat chronic kidney disease in the general population can be reasonably applied to the liver transplant population and include addressing comorbidities such as hypertension and diabetes. Strategies to minimize or withdraw calcineurin inhibitors from the immunosuppressive regimen can slow progression of kidney dysfunction. Patients with advanced chronic kidney disease should be considered for kidney transplantation due to its survival advantage. Allocation policy in the United States confers safety-net allocation priority for liver transplant recipients who develop advanced chronic kidney disease within the first year of liver transplantation.

Disparities in telemedicine utilization among kidney transplant patients during the COVID-19 pandemic: Barriers and opportunities.

INTRODUCTION: The COVID-19 pandemic allowed for the rapid implementation of telemedicine for kidney transplant patients; however, widespread adoption may worsen existing health care inequities among vulnerable populations. This study aimed to characterize telemedicine utilization by kidney transplant patients during the early pandemic with particular attention to healthcare equity. METHODS: A retrospective analysis of kidney transplant patients interacting with telemedicine was performed. Patient demographic data and distance to the transplant center were obtained. The National Center for Health Statistics (NCHS) Urban-Rural Classification Scheme for Counties and Brokamp Neighborhood Deprivation Index (NDI) score were used to characterize patients' counties of residence. Multivariable logistic regression evaluated associations between patient and community characteristics and the likelihood of an encounter being telemedicine. RESULTS: This study included 1033 patients who participated in 3727 encounters from March 11 through October 2020. Characteristics associated with decreased likelihood of telemedicine use were increased age (OR = .993; 95% CI = .986-.999, P = .022), non-White vs. White race (OR = .826, 95% CI = .697-.979; P = .028), male vs. female sex (OR = .746, 95% CI = .632-.880; P < .001), and a higher Brokamp Neighborhood Deprivation Index score (OR = .159; 95% CI = .029-.873; P = .034). The effect of distance to the transplant center on the likelihood of a telemedicine encounter differed by NCHS Urban-Rural designation (interaction P = .018), with its likelihood increasing by 2%-3% with each 10-mile increment among persons residing in medium-, small-, and non-metropolitan counties compared to those residing in the most rural counties. CONCLUSIONS: Telemedicine visits were less often completed by patients of older age, non-white race, male sex, and those residing in counties having higher NDI scores. While telemedicine has the potential to improve healthcare access and decrease costs, proactive efforts need to be taken to mitigate disparities in vulnerable populations.

Characterizing the risk of human leukocyte antigen-incompatible living donor kidney transplantation in older recipients.

Older compatible living donor kidney transplant (CLDKT) recipients have higher mortality and death-censored graft failure (DCGF) compared to younger recipients. These risks may be amplified in older incompatible living donor kidney transplant (ILDKT) recipients who undergo desensitization and intense immunosuppression. In a 25-center cohort of ILDKT recipients transplanted between September 24, 1997, and December 15, 2016, we compared mortality, DCGF, delayed graft function (DGF), acute rejection (AR), and length of stay (LOS) between 234 older (age ≥60 years) and 1172 younger (age 18-59 years) recipients. To investigate whether the impact of age was different for ILDKT recipients compared to 17 542 CLDKT recipients, we used an interaction term to determine whether the relationship between posttransplant outcomes and transplant type (ILDKT vs CLDKT) was modified by age. Overall, older recipients had higher mortality (hazard ratio: 1.632.072.65, P < .001), lower DCGF (hazard ratio: 0.360.530.77, P = .001), and AR (odds ratio: 0.390.540.74, P < .001), and similar DGF (odds ratio: 0.461.032.33, P = .9) and LOS (incidence rate ratio: 0.880.981.10, P = 0.8) compared to younger recipients. The impact of age on mortality (interaction P = .052), DCGF (interaction P = .7), AR interaction P = .2), DGF (interaction P = .9), and LOS (interaction P = .5) were similar in ILDKT and CLDKT recipients. Age alone should not preclude eligibility for ILDKT.

The Perspectives of General Nephrologists Toward Transitions of Care and Management of Failing Kidney Transplants.

The management of failing kidney allograft and transition of care to general nephrologists (GN) remain a complex process. The Kidney Pancreas Community of Practice (KPCOP) Failing Allograft Workgroup designed and distributed a survey to GN between May and September 2021. Participants were invited via mail and email invitations. There were 103 respondents with primarily adult nephrology practices, of whom 41% had an academic affiliation. More than 60% reported listing for a second kidney as the most important concern in caring for patients with a failing allograft, followed by immunosuppression management (46%) and risk of mortality (38%), while resistant anemia was considered less of a concern. For the initial approach to immunosuppression reduction, 60% stop antimetabolites first, and 26% defer to the transplant nephrologist. Communicating with transplant centers about immunosuppression cessation was reported to occur always by 60%, and sometimes by 29%, while 12% reported making the decision independently. Nephrologists with academic appointments communicate with transplant providers more than private nephrologists (74% vs. 49%, p = 0.015). There are heterogeneous approaches to the care of patients with a failing allograft. Efforts to strengthen transitions of care and to develop practical practice guidelines are needed to improve the outcomes of this vulnerable population.

Kidney Failure Patients' Perceptions and Definitions of Health: A Qualitative Study.

Rationale & Objective: Patients with kidney failure who have used multiple treatment modalities are a unique source of information for how different options may best fit their values. We aimed to understand how people interpret their health and kidney failure treatment experience to inform providers who facilitate shared decision-making conversations. Study Design: This qualitative, interpretive phenomenological study explores how patients with kidney failure interpret health throughout their treatment trajectory. Setting & Participants: We recruited a purposive sample of patients who had used 3 or more kidney failure treatment options, including transplant and dialysis from transplant clinics and online support groups, for semi-structured interviews. Eligible participants were over 18 and spoke English for a total of 7 current transplant, 10 current home dialysis, and 1 current in-center patient. Analytical Approach: A 6-step iterative process of data analysis occurred concurrently with data collection. Results: Half of the 18 participants were Black; 67% were women. Three interrelated themes emerged from interviews: ability to engage in meaningful activities; working for balance; and living in context. Participants evaluated health according to their ability to engage in meaningful activities while balancing their emotional and physical needs with their life goals. When their social and treatment environments supported their autonomy, participants also considered themselves healthy. Limitations: The inclusion of only English-speaking patients limits the transferability of findings. A longitudinal design, repeated interviews, observation, and dyadic interviews would increase the health care providers' understanding and interpretation of health. Conclusions: The themes demonstrated patients evaluated health based on ability to engage in meaningful activities while maintaining balance. The treatment context, particularly how health care providers responded to patients' physiological experience, autonomy, and power, influenced interpretation of patient treatment experiences. Integrating patient interpretations of health with quantitative measures of treatment effectiveness can help health care providers better partner with patients to provide effective care for kidney failure.

Current landscape of kidney allocation: Organ procurement organization perspectives.

Organ procurement organizations (OPOs) play a central role in the recovery, preservation, and distribution of deceased donor kidneys for transplantation in the United States. We conducted a national survey to gather information on OPO practices and perceived barriers to efficient organ placement in the face of the new circle-based allocation and asked for suggestions to overcome them. Of the 57 OPOs, 44 responded (77%). The majority of OPOs (61%) reported barriers to obtaining a kidney biopsy, including lack of an available pathologist. Most OPOs (55%) indicated barriers to pumping owing to a lack of available staff and transportation. Respondents agreed or strongly agreed that the new allocation system has worsened transportation challenges (85%), increased provisional acceptances of kidneys (66%), increased communication challenges with transplant centers (68%), and worsened the efficiency of organ allocation (83%). OPO-suggested solutions include making transplant centers more accountable for inefficient selection practices, developing reliable transportation options, and removing the requirement for national sharing. These findings underscore the need to examine closely the trade-offs of the new allocation system with respect to costs, organ ischemia, and discard. These findings may help inform practice and policy for overcoming transportation barriers and improving the efficiency of organ placement.

Neurocognitive Function Changes Following Kidney Transplant: A Prospective Study.

Rationale & Objective: Patients with advanced kidney disease are at risk for cognitive impairment, which may persist after kidney transplantation. We sought to understand changes in neurocognitive function domains utilizing comprehensive cognitive assessments. Study Design: Prospective cohort study. Setting & Population: Single-center study of patients undergoing kidney transplantation. Exposure: Kidney transplantation. Outcomes: Changes in neurocognitive function as measured by the Repeatable Battery for Assessment of Neuropsychological Status (RBANS) and the Trail Making Test Parts A and B (TRAIL A and B) before transplantation (baseline) and compared to 3 months and 12 months posttransplant. Analytical Approach: Wilcoxon signed-rank and linear mixed effect models were utilized to assess changes in neurocognitive scores at 3 months and 12 months compared to baseline. Results: Thirty-two patients were included with a mean age of 45 years, 47% female, 85% White, and 62% with at least some college education. Hypertension and diabetes were etiologies of kidney disease in 31% and 25% of patients, respectively. Baseline RBANS and TRAIL A and B scores averaged 84.7 ± 14, 40.4 ± 9.9, and 41 ± 11.5, respectively. Although there were posttransplant improvements in immediate and delayed memory at 3 months, these were not sustained at 12 months. There were no significant differences from baseline at 3 months and 12 months in RBANS index scores for language, visuospatial/constructional abilities, and attention. Compared to baseline, TRAIL A scores were not significantly different at 3 months but were significantly improved at 12 months, whereas TRAIL B scores improved significantly at both 3 months and 12 months. Limitations: Single-center design and small sample size. Conclusions: Utilizing comprehensive cognitive assessments, we found improvements in attention and executive function in the first posttransplant year as measured by TRAIL A and B. However, there was no significant change in global cognition as measured by RBANS. These findings identify cognitive domains for potential intervention in the posttransplant population.

Telemedicine services for living kidney donation: A US survey of multidisciplinary providers.

Individuals considering living kidney donation face geographic, financial, and logistical challenges. Telemedicine can facilitate healthcare access/care coordination. Yet difficulties exist in telemedicine implementation and sustainability. We sought to examine centers' practices and providers' attitudes toward telemedicine to improve services for donors. We surveyed multidisciplinary providers from 194 active adult US living donor kidney transplant centers; 293 providers from 128 unique centers responded to the survey (center representation rate = 66.0%), reflecting 83.9% of practice by donor volume and 91.5% of US states/territories. Most centers (70.3%) plan to continue using telemedicine beyond the pandemic for donor evaluation/follow-up. Video was mostly used by nephrologists, surgeons, and psychiatrists/psychologists. Telephone and video were mostly used by social workers, while video or telephone was equally used by coordinators. Half of respondent nephrologists and surgeons were willing to accept a remote completion of physical exam; 68.3% of respondent psychiatrists/psychologists and social workers were willing to accept a remote completion of mental status exam. Providers strongly agreed that telemedicine was convenient for donors and would improve the likelihood of completing donor evaluation. However, providers (65.5%) perceived out-of-state licensing as a key policy/regulatory barrier. These findings help inform practice and underscore the instigation of policies to remove barriers using telemedicine to increase living kidney donation.