American Board of Internal Medicine Nephrology Procedure Requirements for Initial Certification: Time for a Change and Pursuing Consensus in the Nephrology Community.

In 1988, the American Board of Internal Medicine (ABIM) defined essential procedural skills in nephrology, and candidates for ABIM certification were required to present evidence of possessing the skills necessary for placement of temporary dialysis vascular access, hemodialysis, peritoneal dialysis, and percutaneous renal biopsy. In 1996, continuous renal replacement therapy was added to the list of nephrology requirements. These procedure requirements have not been modified since 1996 while the practice of nephrology has changed dramatically. In March 2021, the ABIM Nephrology Board embarked on a policy journey to revise the procedure requirements for nephrology certification. With the guidance of nephrology diplomates, training program directors, professional and patient organizations, and other stakeholders, the ABIM Nephrology Board revised the procedure requirements to reflect current practice and national priorities. The approved changes include the Opportunity to Train standard for placement of temporary dialysis catheters, percutaneous kidney biopsies, and home hemodialysis which better reflects the current state of training in most training programs, and the new requirements for home dialysis therapies training will align with the national priority to address the underuse of home dialysis therapies. This perspective details the ABIM process for considering changes to the certification procedure requirements and how ABIM collaborated with the larger nephrology community in considering revisions and additions to these requirements.

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.

Barriers and facilitators to the transplant process among patients living with polycystic kidney disease: a qualitative Approach.

BACKGROUND: Kidney transplant is the gold standard for renal replacement therapy in patients with autosomal dominant polycystic kidney disease (ADPKD), which is the fourth leading cause of kidney failure. Despite the medical and economic benefits of preemptive kidney transplant over dialysis before transplant, only 9-21% of qualifying patients receive preemptive transplants. Given the low rates of preemptive transplant, the aim of this study was to determine perceived facilitators and barriers to preemptive transplant among ADPKD patients using a qualitative approach. METHODS: Data were collected between July 2021 and January 2022 from virtual individual semi-structured interviews of 16 adult participants with ADPKD. Qualitative analysis of the recorded interviews was conducted to generate themes. RESULTS: Our findings revealed two themes specific for facilitators to preemptive transplant (social support and patient agency) and three themes specific to barriers for preemptive transplant (inadequate social support, gaps in knowledge, and institutional and systemic policies). The results also include various subthemes and the application of these themes to the social ecological model. CONCLUSIONS: These findings suggest that increasing social support and patient agency, such as through patient navigator programs and encouraging effective communication between health care providers and patients, can facilitate the transplant process. Increasing dissemination of transplant knowledge from institutions and systems to patients through paired kidney exchange education and live donor outreach can also increase timely access to preemptive kidney transplants for patients with ADPKD. Our findings are limited by our single site study in the US, which may not apply to individuals experiencing different social, cultural, and health access conditions.

Kidney transplant candidacy evaluation and waitlisting practices in the United States and their association with access to transplantation.

There are limited data on the degree of variability in practices surrounding prioritization of referrals for transplant evaluation and criteria for transplant candidacy and their association with transplantation rates. We surveyed transplant programs across the United States between January 2020 and May 2020 to determine current pre-transplantation practices. We examined the relation between these reported practices and the outcomes of waitlisted patients at responding programs between January 2015 and March 2021 using Scientific Registry of Transplant Recipients data. We used adjusted Cox models with random effects to accommodate clustering by program. Primary outcomes included living or deceased donor transplantation. Of 172 surveyed programs, 90 participated. Substantial variations were noted in when the candidacy evaluation began (13% reported when eGFR was <30 mL/min/1.73 m2 and 17% reported no set policy) and the approach to pre-transplantation cardiac workup (multi-modality [58%], stress echocardiogram [20%]). Using adjusted models, a program policy of using other measures of body habitus to determine transplant candidacy rather than requiring patients to meet a body mass index (BMI) threshold of ≤35 kg/m2 (reference group) for candidacy was associated with a higher hazard of living donor transplantation (HR 1.83 [95% CI 1.10-3.03]). Pre-transplant practices vary substantially across the United States, and select practices were associated with transplantation rates.

Sex and gender disparity in kidney transplantation: Historical and future perspectives.

Sex and gender disparity exist in various stages of kidney transplantation. Females were found to be less likely to be referred for kidney transplant, complete pre-transplant evaluation, be placed on the waitlist, and receive a kidney transplant compared to their male counterparts. Interestingly, females comprise the majority of living kidney donors. This review explores the biological and psychosocial factors that contribute to sex and gender disparity in kidney transplantation and proposes ways to address the disparity.

Racial Disparities in Eligibility for Preemptive Waitlisting for Kidney Transplantation and Modification of eGFR Thresholds to Equalize Waitlist Time.

BACKGROUND: Patients may accrue wait time for kidney transplantation when their eGFR is ≤20 ml/min. However, Black patients have faster progression of their kidney disease compared with White patients, which may lead to disparities in accruable time on the kidney transplant waitlist before dialysis initiation. METHODS: We compared differences in accruable wait time and transplant preparation by CKD-EPI estimating equations in Chronic Renal Insufficiency Cohort participants, on the basis of estimates of kidney function by creatinine (eGFRcr), cystatin C (eGFRcys), or both (eGFRcr-cys). We used Weibull accelerated failure time models to determine the association between race (non-Hispanic Black or non-Hispanic White) and time to ESKD from an eGFR of ≤20 ml/min per 1.73 m2. We then estimated how much higher the eGFR threshold for waitlisting would be required to achieve equity in accruable preemptive wait time for the two groups. RESULTS: By eGFRcr, 444 CRIC participants were eligible for waitlist registration, but the potential time between eGFR ≤20 ml/min per 1.73 m2 and ESKD was 32% shorter for Blacks versus Whites. By eGFRcys, 435 participants were eligible, and Blacks had 35% shorter potential wait time compared with Whites. By the eGFRcr-cys equation, 461 participants were eligible, and Blacks had a 31% shorter potential wait time than Whites. We estimated that registering Blacks on the waitlist as early as an eGFR of 24-25 ml/min per 1.73 m2 might improve racial equity in accruable wait time before ESKD onset. CONCLUSIONS: Policies allowing for waitlist registration at higher GFR levels for Black patients compared with White patients could theoretically attenuate disparities in accruable wait time and improve racial equity in transplant access.

Association between Longer Travel Distance for Transplant Care and Access to Kidney Transplantation and Graft Survival in the United States.

BACKGROUND: Transplant candidates may gain an advantage by traveling to receive care at a transplant center that may have more favorable characteristics than their local center. Factors associated with longer travel distance for transplant care and whether the excess travel distance (ETD) is associated with access to transplantation or with graft failure are unknown. METHODS: This study of adults in the United States wait-listed for kidney transplantation in 1995-2015 used ETD, defined as distance a patient traveled beyond the nearest transplant center for initial waiting list registration. We used linear regression to examine patient and center characteristics associated with ETD and Fine-Gray models to examine the association between ETD (modeled as a spline) and time to deceased or living donor transplantation or graft failure. RESULTS: Of 373,365 patients, 11% had an ETD≥50 miles. Traveling excess distance was more likely among patients who were of non-Black race or those whose nearest transplant center had lower annual living donor transplant volume. At an ETD of 50 miles, we observed a lower likelihood of deceased donor transplantation (subhazard ratio [SHR], 0.85; 95% confidence interval [95% CI], 0.84 to 0.87) but higher likelihood of living donor transplantation (SHR, 1.14; 95% CI, 1.12 to 1.16) compared with those who received care at their nearest center. ETD was weakly associated with higher risk of graft failure. CONCLUSIONS: Patients who travel excess distances for transplant care have better access to living donor but not deceased donor transplantation and slightly higher risk of graft failure. Traveling excess distances is not clearly associated with better outcomes, especially if living donors are unavailable.

The failing kidney allograft: A review and recommendations for the care and management of a complex group of patients.

The return to dialysis after allograft failure is associated with increased morbidity and mortality. This transition is made more complex by the rising numbers of patients who seek repeat transplantation and therefore may have indications for remaining on low levels of immunosuppression, despite the potential increased morbidity. Management strategies vary across providers, driven by limited data on how to transition off immunosuppression as the allograft fails and a paucity of randomized controlled trials to support one approach over another. In this review, we summarize the current data available for management and care of the failing allograft. Additionally, we discuss a suggested plan for immunosuppression weaning based upon the availability of re-transplantation and residual allograft function. We propose a shared-care model in which there is improved coordination between transplant providers and general nephrologists so that immunosuppression management and preparation for renal replacement therapy and/or repeat transplantation can be conducted with the goal of improved outcomes and decreased morbidity in this vulnerable patient group.

Kidney recipients with allograft failure, transition of kidney care (KRAFT): A survey of contemporary practices of transplant providers.

Kidney allograft failure and return to dialysis carry a high risk of morbidity. A practice survey was developed by the AST Kidney Pancreas Community of Practice workgroup and distributed electronically to the AST members. There were 104 respondents who represented 92 kidney transplant centers. Most survey respondents were transplant nephrologists at academic centers. The most common approach to immunosuppression management was to withdraw the antimetabolite first (73%), while only 12% responded they would withdraw calcineurin inhibitor (CNI) first. More than 60% reported that the availability of a living donor is the most important factor in their decision to taper immunosuppression, followed by risk of infection, risk of sensitization, frailty, and side effects of medications. More than half of respondents reported that embolization was either not available or offered to less than 10% as an option for surgical intervention. Majority reported that ≤50% of failed allograft patients were re-listed before dialysis, and less than a quarter of transplant nephrologists performed frequent visits with their patients with failed kidney allograft after they return to dialysis. This survey demonstrates heterogeneity in the care of patients with a failing allograft and the need for more evidence to guide improvements in clinical practice related to transition of care.

Report from the American Society of Transplantation on frailty in solid organ transplantation.

A consensus conference on frailty in kidney, liver, heart, and lung transplantation sponsored by the American Society of Transplantation (AST) and endorsed by the American Society of Nephrology (ASN), the American Society of Transplant Surgeons (ASTS), and the Canadian Society of Transplantation (CST) took place on February 11, 2018 in Phoenix, Arizona. Input from the transplant community through scheduled conference calls enabled wide discussion of current concepts in frailty, exploration of best practices for frailty risk assessment of transplant candidates and for management after transplant, and development of ideas for future research. A current understanding of frailty was compiled by each of the solid organ groups and is presented in this paper. Frailty is a common entity in patients with end-stage organ disease who are awaiting organ transplantation, and affects mortality on the waitlist and in the posttransplant period. The optimal methods by which frailty should be measured in each organ group are yet to be determined, but studies are underway. Interventions to reverse frailty vary among organ groups and appear promising. This conference achieved its intent to highlight the importance of frailty in organ transplantation and to plant the seeds for further discussion and research in this field.

Management of Kidney Transplant Recipients by General Nephrologists: Core Curriculum 2019.

Kidney transplantation is associated with improvement in quality of life and mortality as compared to remaining on dialysis. It is therefore the optimal treatment for kidney failure for most patients. While transplantation nephrologists typically care for the patient in the first 6 months posttransplantation, general nephrologists and internists often care for kidney transplant recipients after this period. Medical management of the kidney transplant recipient can be challenging, and primary care physicians and nephrologists may be unfamiliar with the medical nuances of caring for these patients. This includes drug interactions, which are common and can result in drug toxicities, rejection, and graft injury. Infections and malignancies related to long-term immunosuppression may pose diagnostic and treatment challenges. In this article, we review the mechanisms of immunosuppression, types of rejection, complications of recurrent disease, common infectious diseases, and the nonrenal complications commonly encountered in the kidney transplant recipient.

Disaster preparation in kidney transplant recipients: a questionnaire-based cohort study from a large United States transplant center
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BACKGROUND: Few quantitative assessments have assessed disaster preparation in kidney transplant patients. This is a survey-based assessment of disaster preparedness of 200 patients at the University of California San Francisco, USA. MATERIALS AND METHODS: Patients answered questionnaires assessing their level of preparedness as well as barriers to preparation. Preparedness was scored based on response to 7 questions. Univariate analyses compared participant characteristics extracted from the medical chart against three tertiles of preparedness: low (scores 0 - 2), medium (scores 3 - 4), and high (scores 5 - 7). California counties were coded and mapped by average preparedness scores. RESULTS: Only 30% of patients were highly prepared for disasters. Participants were prepared with available medication for 2 weeks (78.5%) and least prepared in having a medical ID bracelet (13%). Significant minorities of patients (40% of patients or more) were unprepared with lists of medications, important phone numbers and disaster kits. Preparedness was not associated with demographic and clinical characteristics. Monterey County was the most prepared of the 31 California counties sampled (score of 4.25 out of 7). CONCLUSION: All patients should be educated regarding disaster preparation. County and medical services should collaborate to address specialized populations in general preparedness planning.
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Barriers and Facilitators to Exercise in Older Adults Awaiting Kidney Transplantation and Their Care Partners.

Rationale & Objective: Despite guidelines calling to improve physical activity in older adults, and evidence suggesting that prekidney transplant physical function is highly associated with posttransplant outcomes, only a small percentage of older patients treated with dialysis are engaged in structured exercise. We sought to elucidate barriers and facilitators of exercise among older adults treated with dialysis awaiting transplant and their care partners. Study Design: Individual, in-depth, cognitive interviews were conducted separately for patients and care partners through secure web-conferencing. Setting & Participants: Twenty-three patients (≥50 years of age, treated with dialysis from the University of San Francisco kidney transplantation clinic, with a short physical performance battery of ≤10) and their care partners. Analytical Approach: All audio interviews were transcribed verbatim. Three investigators independently coded data and performed qualitative thematic content. The interview guide was updated iteratively based on the Capability Opportunity Motivation Behavior model. Results: Patients' median age was 60 years (57 ± 63.5) and care partners' median ages was 57 years (49.5 ± 65.5). Thirty-nine percent of patients and 78% of care partners were female, 39% of patients and 30% of care partners self-identified as African American, and 47% of dyads were spouse or partner relationships. Major themes for barriers to pretransplant exercise included lack of understanding of an appropriate regimen, physical impairments, dialysis schedules, and safety concerns. Major facilitators included having individualized or structured exercise programs, increasing social support for patients and care partners, and motivation to regain independence or functionality or to promote successful transplantation. Limitations: Participants geographically limited to Northern California. Conclusions: Although patients and care partners report numerous barriers to pretransplant exercise and activity, they also reported many facilitators. An individualized, structured, home-based exercise program could circumvent many of the reported barriers and allow older patients to improve pretransplant physical function.

Although exercise can improve the fitness of older adults treated with dialysis for kidney transplantation and reduce posttransplant complications, many such individuals do not exercise. We sought to elicit perspectives on barriers and facilitators to prekidney transplant exercises from older adults treated with dialysis and their care partners. We found that although patients and care partners had unique perspectives, they shared many barriers (such as physical and/or cognitive impairment, difficulty scheduling around dialysis, lack of guidance on exercise, and reduced exercise motivation related to dialysis) and several facilitators (such as desire to regain functionality and participate in life and motivation for successful transplantation). A shared interest among patients and care partners in joint participation in structured and home-based exercise may represent a tool to overcome barriers to pretransplant exercise.

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.

Inadequacy of cardiovascular risk factor management in chronic kidney transplantation - evidence from the FAVORIT study.

BACKGROUND: Kidney transplant recipients (KTRs) have increased risk of cardiovascular disease (CVD). Our objective is to describe the prevalence of CVD risk factors applying standard criteria and use of CVD risk factor-lowering medications in contemporary KTRs. METHODS: The Folic Acid for Vascular Outcome Reduction in Transplantation study enrolled and collected medication data on 4107 KTRs with elevated homocysteine and stable graft function an average of five yr post-transplant. RESULTS: CVD risk factors were common (hypertension or use of blood pressure (BP) lowering medication in 92%, borderline or elevated low-density lipoprotein (LDL) or use of lipid-lowering agent in 66%, history of diabetes mellitus in 41%, and obesity in 38%); prevalent CVD was reported in 20% of study participants. National Kidney Foundation BP guidelines (BP <130/80 mmHg) were not met by 69% of participants. Uncontrolled hypertension (BP of 140/90 mmHg or higher) was present in 44% of those taking antihypertension medication; 18% of participants had borderline or elevated LDL, of which 60% were untreated, and 31% of the participants with prevalent CVD were not using an antiplatelet agent. CONCLUSION: There is opportunity to improve treatment and control of traditional CVD risk factors in kidney transplant recipients.

Management of Hospitalized Kidney Transplant Recipients for Hospitalists and Internists.

The number of kidney transplant recipients has grown incrementally over the years. These patients have a high comorbidity index and require special attention to immunosuppression management. In addition, this population has an increased risk for cardiovascular events, electrolyte abnormalities, allograft dysfunction, and infectious complications. It is vital for hospitalists and internists to understand the risks and nuances in the care of this increasingly prevalent, but also high-risk, population.

Comparison of 2021 CKD-EPI Equations for Estimating Racial Differences in Preemptive Waitlisting for Kidney Transplantation.

BACKGROUND AND OBJECTIVES: Wait time for kidney transplantation can accrue when GFR is ≤20 ml/min. We examined whether using the race-free 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations to guide preemptive waitlisting could attenuate racial differences in accruable preemptive wait time. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Our retrospective cohort study included Black or White Chronic Renal Insufficiency Cohort (CRIC) participants who were theoretically eligible for waitlist registration. We used Weibull accelerated failure time models to determine the association between race (Black or White) and time to kidney failure from the qualifying visit when the eGFR by creatinine or creatinine-cystatin C 2021 CKD-EPI equations fell to ≤20 ml/min per 1.73 m2. We then tested for differences in the time ratios from models using the 2021 creatinine- or creatinine-cystatin C-based CKD-EPI equation through a bootstrapping approach. RESULTS: By the creatinine equation, 472 CRIC participants were theoretically eligible for waitlist registration, and potential preemptive wait time was similar for Black versus White participants (time ratio, 1.05; 95% confidence interval, 0.81 to 1.35). The median wait time by the creatinine equation that could be accrued for Black participants was 23 versus 22 months in White participants. By the creatinine-cystatin C equation, 441 CRIC participants were eligible, and potential wait time was 20% shorter (95% confidence interval, 0.62 to 1.02) for Black than White participants. The median wait time that could be accrued for Black participants was 21 versus 26 months for White participants when using the creatinine-cystatin C equation. Using bootstrapping, the ratio of the time ratio of the models using the creatinine versus creatinine-cystatin C equation was statistically significantly different (ratio of the time ratios = 1.31 with 95% confidence interval, 1.06 to 1.62). CONCLUSIONS: Use of the 2021 creatinine-based CKD-EPI equation to determine preemptive waitlist eligibility reduced racial differences in preemptive wait time accrual more than use of the creatinine-cystatin C 2021 CKD-EPI equation within a theoretical context.

Solid-Phase C1q/C3d Fixing Readouts Correlate with High Median Fluorescence Intensity (MFI) De Novo Donor-Specific HLA Antibodies and C4d⁺ Antibody-Mediated Rejection in Kidney Transplant Recipients.

BACKGROUND Solid-phase assays to investigate the complement-activating capacity of HLA antibodies have been utilized to optimize organ allocation and improve transplant outcomes. The clinical utility of C1q/C3d-binding characteristics of de novo donor-specific anti-HLA antibodies (dnDSA) associated with C4d-positive antibody-mediated rejection (C4d⁺ AMR) in kidney transplants (KTx) has not been defined. MATERIAL AND METHODS Sera from 120 KTx recipients that had dnDSA concurrent with protocol/cause biopsy (median 3.8 years after transplantation) were screened for C1q and C3d-binding dnDSA. The difference in the incidence of C4d⁺ AMR between recipients with and without C1q/C3d-binding dnDSA was assessed. RESULTS Over 86% of dnDSAs were class II antibodies. The immunodominant dnDSAs characterized by the highest median fluorescence intensity (MFI) in most recipients were HLA-DQ antibodies (67%). Most recipients (62%, n=74) had either C1q⁺ (56%), C3d⁺ (48%), or both C1q⁺C3d⁺ (41.2%) dnDSA, while the remaining 38% were negative for both C1q and C3d. Of those with C1q⁺/C3d⁺ dnDSA, 87% had high-MFI IgG (MFI=14144±5363 and 13932±5278, respectively), while 65% of C1q⁻C3d⁻ dnDSA had low-MFI IgG (MFI=5970±3347). The incidence of C4d+ AMR was significantly higher in recipients with C1q⁺ (66%), C3d+ (74%), and C1q⁺C3d⁺ (72%) dnDSA than in those with C1q⁻C3d⁻ dnDSA (30%) recipients. Recipients with C3d⁺/C1q⁺ dnDSA had higher C4d⁺ scores on biopsy. CONCLUSIONS C1q⁺/C3d⁺ dnDSA were associated with C4d⁺ AMR and high-IgG MFI. Our data call into question the predictive utility of C1q/C3d-binding assays in identifying KTx recipients at risk of allograft failure. In conclusion, IgG MFI is sufficient for clinical management, and the C1q/C3d-assays with added cost do not provide any additional information.

Association of Physical Function and Survival in Older-Adult Renal Transplant Recipients.

There is an increase in older-adult renal transplant recipients in United States. The objective of this study was to assess the association between physical function (PF) and patient survival in renal transplant recipients who are aged 65 years or older. Using United Network for Organ Sharing (UNOS) data from 2007 to 2016, renal transplant recipients aged 65 years or older were included. Multivariable Cox regression was used to assess associations between survival and functional status adjusted for age, sex, race, donor quality, diabetes, and dialysis vintage. The study identified 26,721 patients. Patient survival was significantly higher in recipients who needed no assistance and lowest in patients in need of total assistance (P < .0001). In deceased donor (DD) transplants, the relative risk for mortality was 2.06 (1.74-2.43) for total assistance and 1.17 (1.08-1.28) for moderate assistance compared to no assistance (P < .0001). In living donor (LD) transplants, the relative risk of mortality was 1.38 (0.78-2.42) for patients needing total assistance and 1.37 (1.14-1.65) for patients needing moderate assistance compared to patients who did not need assistance (0.003). PF is an independent predictor of post-transplant mortality. Assessment of older potential renal transplant recipients should include assessment and standardization of functional status to counsel about post-transplant survival.