INTRODUCTION Live kidney donors (LKDs) of African ancestry have a higher risk for developing end-stage kidney disease (ESKD) than demographically matched healthy nondonors.1 Retrospective data from the general population reveal that having 2 apolipoprotein L1 gene (APOL1) kidney-risk variants (KRVs) (ie, G1G1, G2G2, or G1G2) contributes to this risk.2 Two APOL1 KRVs vary in frequency around the world with approximately 11%–32% in African Americans (AAs), sub-Saharan Africans, and Western Africans, 5%–22% in Afro-Brazilians, Afro-Caribbeans, or Black Hispanics/Latinx, and approximately 0% in European Americans.3 APOL1 genetic testing is available, and in the absence of prospective data, the role of APOL1 genotyping in LKD candidate selection remains uncertain. Recent survey data reported wide variation in genetic testing practices and clinical use of results during the donor selection process.4 There are several ethical issues concerning the use of genetic testing to determine donor eligibility, which are central to development of policy around APOL1 genetic testing, release of results, and counseling.5 The National Institutes of Health initiated the prospective multicenter U01 “APOL1 Long-term Kidney Transplantation Outcomes Network” (APOLLO) to help understand the impact of APOL1 KRVs on long-term kidney function of donors and recipient outcomes.6 As the transplant community awaits the results of definitive research, the American Society of Transplantation’s Living Donor Community of Practice commissioned a workgroup to develop interim recommendations for APOL1 genetic testing. The workgroup, comprising a transplant nephrologist, a transplant surgeon, a nephrologist with expertise in genetics, a former LKD of African ancestry, a general nephrologist, and a bioethicist, produced this report. APOL1 and Native Kidney Disease The discovery of the association of APOL1 KRVs and chronic kidney disease (CKD) revealed that unrelated forms of nondiabetic nephropathy comprise a spectrum of APOL1-related diseases, including hypertension-attributed nephropathy, focal segmental glomerulosclerosis, HIV-associated nephropathy, and severe lupus nephritis.7 However, most people with 2 APOL1 KRVs do not develop ESKD. Second hits or modifying factors such as viral infections are required to initiate kidney disease.8 APOL1 and Deceased Donor Kidney Transplantation Kidneys transplanted from deceased donors with 2 APOL1 KRVs are associated with premature allograft failure and a ~2-fold increased risk of allograft loss compared with kidneys from donors with 1 or 0 APOL1 KRVs.9 Similar to native kidney disease, a second insult may be required to develop allograft failure after transplanting kidneys from AA deceased donors carrying 2 APOL1 KRVs. APOL1 and Former Living Kidney Donors A cohort of 136 AA LKDs with postdonation follow-up information was stratified by APOL1 genotype.10 Donors with 2 APOL1 KRVs had lower predonation and postdonation estimated glomerular filtration rates (eGFRs) and faster annual declines in eGFR than donors with 0 or 1 KRV (1.19 versus 0.4 mL/min/1.73 m2 per y; P = 0.02). Of 19 donors carrying 2 APOL1 KRVs, 2 (11%) developed ESKD. However, the 11% frequency of ESKD in LKDs with 2 APOL1 KRVs in this study may not be an accurate estimate because of the small sample size and inability to genotype all eligible participants. APOL1 and Risk of Kidney Disease in Young, Healthy Potential Donors A cohort of 3438 individuals aged 18–30 y who were deemed medically suitable to donate was retrospectively assessed for development of CKD stage 3 or higher after 25 y.11 Among the 18-y olds, the 25-y projected CKD risk was higher in AAs than Whites and varied by sex. The risk of CKD increased further among those with 2 APOL1 KRVs. The risk of CKD was much greater for individuals with 2 APOL1 KRVs who presented with relative contraindications for donation, including impaired fasting blood sugar, body mass index >30 kg/m2, eGFR 90–99 mL/min/1.73 m2, smoking, and a family history of hypertension and diabetes. Based on the risk calculator in this article, an 18-y-old male individual with 2 APOL1 KRVs and no other risk factors was anticipated to have an equivalent risk of CKD as a 30-y-old AA female individual with a family history of diabetes and 0 APOL1 KRVs. The risk of CKD associated with APOL1 KRVs was similar to some of the other risk factors that routinely appear during donor evaluation and generally do not raise similar concerns among transplant professionals. Providers’, AA LKDs’, and Community Members’ Attitudes About APOL1 Testing In a recent survey of transplant nephrologists, transplant surgeons, and community nephrologists, most physicians believed that all potential AA LKDs should be informed about the option of APOL1 testing.12 Similarly, AA LKDs and members of the public recommended that APOL1 testing be routinely offered to donors in clinical care to foster informed decision making about donation.13,14 Half of the surveyed physicians would not proceed or strongly recommend against donation in potential LKDs carrying 2 APOL1 KRVs. However, both AA LKDs and members of the public opposed it as such a policy would violate donor autonomy.13,15 Instead, most community members preferred that the physician and potential LKD together make a shared decision about donation.14 Considering the Available Information, the AST LDCoP APOL1 Workgroup Proposes the Following Guidelines: 1. Who should be educated, by whom, and when? All potential LKD candidates who self-report African ancestry (including AA, Afro-Caribbeans, and Hispanic/Latinx Blacks, Africans) should be informed about the APOL1 gene and risk of ESKD. Although individuals from North Africa and those with mixed ancestry are less likely to carry 2 APOL1 KRVs, they should still be informed about APOL1 and the lower likelihood of carrying 2 APOL1 KRVs. Providers should ask potential donors about their ancestry and ethnic identity rather than rely on their own perceptions or medical records. Counseling can be provided by a transplant team member under the guidance of a transplant nephrologist early in the evaluation process. 2. Who should be tested? AA LKD candidates with known independent risk factors for the development of ESKD such as young age (<44 y), male gender, history of smoking, obesity (body mass index >30 kg/m2), hypertension, low to normal eGFR (90–99 mL/min/1.73 m2), and a family history of ESKD, hypertension, or diabetes in a first-degree relative may be considered for testing. Among donor candidates with 2 or more of these risk factors, the absence of 2 APOL1 KRVs has not been reported to mitigate their future risk of ESKD; such individuals should be counseled about their elevated risk of ESKD before genetic testing.16 For LKD candidates who want to pursue donation after adequate discussion and their risk of ESKD is deemed acceptable by the transplant center, genetic testing for APOL1 KRVs may be offered for further risk stratification. Genetic testing should only be offered after appropriate counseling. LKDs who wish to donate, regardless of their genetic test result, should be allowed to proceed if their risk of ESKD does not exceed the acceptable threshold set by their transplant program. 3. When should testing be offered? If genetic testing is deemed appropriate, it should only be offered to candidates who have passed preliminary medical and psychosocial evaluation, preferably not during the initial screening. This approach is less expensive and provides physicians with the chance to counsel potential LKDs when they have a clinical or laboratory abnormality that may preclude them from donation, regardless of genotype. APOL1 testing may be performed before HLA typing, crossmatching, or computed tomography scanning, because these tests are less likely to rule out donors. 4. What topics should be covered in counseling? Transplant programs should address the pros and cons of APOL1 genetic testing before ordering the test. They should acknowledge the lack of robust data on the postdonation risk of ESKD in potential LKDs carrying 2 APOL1 KRVs and discuss the small study reporting an 11% risk of ESKD 12 y after donation. Programs should also inform potential LKDs that not all individuals carrying 2 APOL1 KRVs develop kidney disease and “second-hits” are required for deterioration in kidney function. Currently, the nature of second hits beyond certain viral infections is unknown. Transplant programs should inform LKD candidates about the national APOLLO study so that candidates can stay apprized of the study results in their decision to donate. The results of the APOLLO study will improve our understanding of the risks involved in donating among individuals with 2 APOL1 KRVs. Other topics of discussion should include, but are not limited to, the lack of specific treatments to prevent APOL1-associated kidney disease, the risk to themselves and to the potential recipient of not donating, and the possibility of psychological distress upon learning that potential LKDs have 2 APOL1 KRVs. Finally, counseling should discuss the role of the Genetic Information Nondiscrimination Act in protecting donors from employer and insurance-based discrimination. Counseling should be offered by a genetic counselor, nephrologist, or transplant team member trained to deliver counseling about APOL1 before donation and to deliver counseling with results thereafter. 5. How should positive test results be approached? The workgroup supports shared decision making between the transplant team and potential LKDs about donating in the context of APOL1 KRVs. Shared decision making entails 2-way communication between donors expressing their preferences and values and providers disclosing information about the procedure, its risks, benefits, and alternatives, out of respect for donor autonomy. As with other single risk factors, the isolated finding of 2 APOL1 KRVs should not be enough to automatically exclude the donor candidate. The presence of ≥2 baseline risk factors for future ESKD (including 2 APOL1 KRVs and other risk factors listed above) should be considered in the informed consent discussion.11 However, the team that recognizes the donor-recipient relationship may influence the donor’s decision. Some potential LKDs may wish to donate despite being informed of their increased future risk for ESKD; other LKDs may want the physician to decide for them. In either case, the risk of ESKD in the donor should be lower than the established acceptable threshold for the transplant center. 6. Should recipients be informed of the living donor’s genotype? To protect the donor’s privacy, the transplant team should not reveal the donor candidate’s APOL1 genotype to the recipient. Donors should decide whether they wish to discuss their genetic test results with the recipient and with family members. If the LKD candidate requests and the potential recipient agrees, transplant programs can jointly discuss genotype results and their implications with the pair. 7. Should a donor with 2 APOL1 KRVs be discouraged to donate because of concerns about recipient outcomes? Currently, no data exist on the impact of the living donor APOL1 genotype on recipient outcomes. The currently available data suggest that transplantation from a LKD, even with 2 APOL1 KRVs, is better for the recipient’s health than remaining on dialysis or waiting to receive a transplant from a deceased donor. 8. Who should bear the cost of APOL1 genotyping? Testing costs range from $300 to $500 and should be covered as a part of the Organ Acquisition Cost by the transplant center. SUMMARY AND FUTURE DIRECTIONS Results of the NIH-funded APOLLO study will not be available to inform clinical practice for several years. Until then, APOL1 genetic testing may supplement the already comprehensive donor evaluation process, as needed, for risk stratification and may be ordered after appropriate counseling has been provided. The decision to donate, in the case of a high-risk genotype, should be handled through shared decision making. Such an approach resonates with LKDs and community members because it addresses matters of consent and donor autonomy. These recommendations are intended to guide transplant centers in developing their own policies around APOL1 genetic testing and donor acceptance criteria. While the transplant community must await new findings and continue to improve its understanding of donor ESKD risk, there should not be a rush to pronounce judgment on the significance of APOL1 KRVs in living donors until firm data are available. ACKNOWLEDGMENTs This article is a work product of the American Society of Transplantation’s Live Donor Community of Practice.
Abstract Recent Findings Black and Hispanic patients carry higher burden of kidney disease, yet have lower access to LDKT. Until recently, these differences were thought to be due to medical co-morbidities and variation in transplant center practices. However, recent studies have shown that systemic and structural inequities related to race may be one of the major drivers. Purpose of Review In this paper, we examine the definition of race and systemic racism, then describe patient-, transplant center–, and society-level barriers to LDKT. We identify how social determinants, cultural biases and mistrust in medical system, influence behaviors, and provider racial profiling affects all phases of transplant evaluation. Finally, we discuss initiatives to overcome some of these barriers, starting from federal government, national organizations, transplant centers, and community partners. Summary Examining structural biases in transplant practices is an important step to developing solutions to address disparities in health care access and outcomes for patients who need and receive transplants.
Abstract: The increasing prevalence of acute renal failure (ARF) patients with hemodynamic intolerance of intermittent hemodialysis (HD), generally because of septic vasoparesis or severe cardiac dysfunction, has led to the development of several strategies to improve the delivery of renal replacement therapy (RRT) in ARF patients. Intradialytic hypotension (IDH) is caused by the interaction of dialysis‐dependent and dialysis‐independent factors. Dialysis‐dependent factors include the prescriptions for fluid removal, solute removal, and dialysate components such as sodium, buffer, and calcium. Dialysis‐ independent factors include hemodynamic compromise caused by hypovolemic, cardiogenic, vasodilatory, and mixed mechanisms. We propose an approach to the prevention and management of IDH in critically ill ARF patients, which minimizes hypovolemic, cardiogenic, and vasodilatory insults by optimizing fluid removal, cardiac function, and vascular contractility.
The management of a kidney transplant program has evolved significantly in the last decades to become a highly specialized, multidisciplinary standard of care for end-stage kidney disease. Transplant center job descriptions have similarly morphed with increasing responsibilities to address a more complex patient mix, increasing medical and surgical therapeutic options, and increasing regulatory burden in the face of an ever-increasing organ shortage. Within this evolution, the role of the Kidney Transplant Medical Director (KTMD) has expanded beyond the basic requirements described in the United Network for Organ Sharing bylaws. Without a clear job description, transplant nephrology trainees may be inadequately trained and practicing transplant nephrologists may face opaque expectations for the roles and responsibilities of Medical Director. To address this gap and clarify the key areas in which the KTMD interfaces with the kidney transplant program, American Society of Transplantation (AST) formed a Task Force of 14 AST KTMDs to review and define the role of the KTMD in key aspects of administrative, regulatory, budgetary, and educational oversight of a kidney transplant program.
Kidney dysfunction has been associated with increased patient morbidity and mortality among multiorgan transplant recipients, including liver transplant recipients.A number of factors contribute to acute and chronic kidney injury in patients with end-stage liver disease (ESLD) including hemodynamic disturbances, drug toxicity, and progression of underlying kidney disease. .Baseline kidney function reflecting renal reserve is an important predictor of patient
Introduction Nephrologists are responsible for the care of patients with a diverse array of systemic diseases, comorbidities, and kidney issues across a variety of service locations (clinic, inpatient, dialysis unit). As the field of nephrology becomes increasingly complex, there has been a need for advanced training and subspecialization, similar to the transformation cardiology experienced with heart failure, electrophysiology, and interventional cardiology. As a result, the American Society of Nephrology (ASN) formed the ASN Task Force on Academic Nephrologist Compensation and Productivity to begin to understand the needed transformation, especially as it relates to assessing clinical productivity and compensation. Members of the task force included nephrology division chiefs, transplant program directors, and transplant nephrologists, representing academic and community transplant programs across the United States. The group met virtually throughout 2021 to discuss specific job functions, roles, responsibilities, and compensation models, and the discussion and conclusions follow. The flow of transplant funds from the hospital to the physician and transplant nephrology models of care are further discussed in a companion Perspective (1). Transplant Nephrologist Roles and Responsibilities Kidney transplant is the preferred treatment for most patients with ESKD. Transplant nephrologists are involved in the management of patients before and after transplant, with responsibilities that include evaluation and waitlisting of appropriate patients referred for transplantation, ensuring that patients remain qualified while on the waiting list, and living donor evaluation, as well as short- and long-term management of immunosuppressive therapy and allograft dysfunction. In many cases, the transplant nephrologist acts as the patient's primary care physician. For optimal patient care, transplant nephrologists must be in constant communication with other providers, including but not limited to referring nephrologists, medical consultants, transplant surgeons, pathologists, histocompatibility laboratory personnel, dialysis teams, and transplant coordinators. With improving outcomes and an increasing number of kidney transplants performed, the responsibility of routine postoperative and hospital care has gradually shifted from the surgeon to the transplant nephrologist, and the volume of patients is cumulative as more survive longer, often presenting management challenges that general nephrologists or other primary care providers are unable to address. This has also led to an exponential increase in the number of clinic visits and staff needed to properly follow patients. Transplantation is regulated by the US Department of Health and Human Services through the Organ Procurement and Transplantation Network. Each transplant program is required to name a primary transplant physician (who usually serves as the medical director) who must maintain current working knowledge of kidney transplantation and perform administrative, regulatory, and budgetary oversight of the program (2). The medical director also connects medical and surgical care to ensure coordination of care and program success, yet there is no standard for protected time for these activities. Outreach is required to maintain the waiting list and involves travel time and interaction with multiple providers and health systems. The medical director and other transplant nephrologists are also heavily involved with the evaluation of new candidates and care coordination to maintain the waiting list. The Renal Physician Association surveys show that, regardless of program size, a wide range of effort (10%–50%) is required to deliver these services, none of which generate relative value units (RVUs). Compensation The Omnibus Budget Reconciliation Act set into motion the implementation in the early 1990s of the Resource-Based Relative Value System (RBRVS) as an effort to reduce health care costs (3). The RBRVS informs the Medicare Fee Schedule by way of the RVU assigned to a particular procedure or service. Relative value is determined by the resources expended on a specific service and quantified by an RVU assigned to that service. Three components make up the total RVU of a given service: physician work effort, practice cost, and relative risk associated with that service. After adjustment for geographic factors, the total RVU for a procedure or service is determined by the sum of the physician work, the practice expense, and malpractice RVU components multiplied by the conversion factor (the dollar amount used to calculate Medicare reimbursement). RVUs have become the dominant currency to assess clinical productivity for compensation (2,4–6). Benchmarks established by health care performance improvement companies, such as Vizient and the Medical Group Management Association, are often utilized by institutions to measure the value of clinical work and to assess clinician productivity. However, as no benchmarks are specific to the encounter of the patient in transplant nephrology, each program has devised its own "productivity" metric for it. The result is a wide range of disparate expectations and targets across the country. Furthermore, many duties of the transplant nephrologist are not captured in a single patient encounter and therefore are not reflected in the RVU: for example, managing patients, reviewing records, talking to referring physicians, attending selection committee meetings, supervising transplant coordinators, traveling to outreach clinics, and teaching. These nonpatient encounter activities occupy a substantial portion of the transplant nephrologists' time and effort and are crucial to successful outcomes, but they are often unrecognized and uncompensated (7). In contrast to payments for individual clinic or inpatient encounters or provision of dialysis services, revenue for many of the non–RVU-generating activities for donors and recipients is included in the global payment to transplant centers as specified in the Centers for Medicare & Medicaid Services Conditions of Participation (Figure 1). Operative care and perioperative care are also compensated for from this global payment on the basis of the transplantation procedure as a capitated payment. A substantial component of this perioperative care is provided by transplant nephrologists. A portion of the additional cost to a hospital of having a transplant program is recoverable as organ acquisition via the Medicare Cost Report. The overall contribution of a transplant physician to the health care system via pretransplant evaluation, testing, radiology, cardiology, histocompatibility testing, waiting list workup, transplant event, infusion suites, pharmacy expenses, and post-transplant care, along with pharmacy revenues, must be analyzed as a whole to understand its financial effect (8,9). Thus, a significant portion of services provided by the transplant nephrologist to both recipients and donors is not billable, yet it is reimbursed to the transplant center or the hospital. However, this funding rarely finds its way back to support transplant nephrology.Figure 1.: Transplant global payment structure: compensated and uncompensated components of care. CMS, Centers for Medicare & Medicaid Services; HLA, human leukocyte antigen testing; UNOS, United Network for Organ Sharing.Transplant Nephrology Compensation Survey In July 2019, the American Society of Transplantation (AST) commissioned a task force of 14 kidney transplant medical directors representing programs of varying size, locations, and practice affiliations to administer a compensation and job satisfaction survey, which was distributed to 809 nephrology members of AST in 2020. Of the 260 respondents included in final analyses, 175 (67%) were affiliated with a university hospital, 56 (22%) were affiliated with a nonuniversity hospital, 25 (10%) were in community practice, and four (1%) were affiliated with the Veterans Administration. Academic rank was evenly distributed; 218 (84%) spent 50% or more of their time performing transplant-related clinical activities, and 117 (45%) had at least one major administrative title, such as transplant center director or kidney/kidney-pancreas medical director. The base compensation was fixed for the majority (90%), and for the remaining, it varied on the basis of wRVU, cash collections, and other parameters. One third of respondents did not receive any incentives above their base salary. All spent time performing nonbillable services; only a third were aware of receiving some compensation for this work, and 154 (56%) were unsure. RVUs were tracked and reported in 194 (76%), but only 107 (44%) were aware of an RVU target; of these, 102 were working at a university hospital. Job satisfaction was associated with total compensation. Although limited by its small sample size, the survey highlights variation in assessing the clinical productivity of a transplant nephrologist and reimbursing for vital nonbillable services. In conclusion, determination of appropriate compensation for transplant nephrologists is complicated. Beyond wRVU metrics, there is a need to compensate for the important nonbillable activities performed by transplant nephrology in ensuring successful access and outcomes of patients undergoing kidney transplants and contributions to the overall success of a transplant center in fulfilling its mission. The changing dynamic of kidney transplantation requires health systems to recognize and support all components of the team approach now essential to a successful program, with transplant nephrologists playing an essential role. Disclosures D.C. Brennan reports consultancy agreements with CareDx, Medeor, Sanofi, and Veloxis; research funding from Allovir, Amplyx, CareDx, and Natera; honoraria from CareDx, Sanofi, and Veloxis; and serving in an advisory or leadership role for the editorial board of Transplantation and UpToDate. R.S. Gaston reports employment with CTI Clinical Trial and Consulting, Inc. and ownership interest in AbbVie Pharmaceuticals, Eli Lilly and Co., Merck and Co., Organon and Co., and Pfizer, Inc. S.B. Gurley reports spouse's employment with United Therapeutics. M.A. Josephson reports consultancy agreements with Exosome Diagnostics, IMMUCOR, Labcorp, Otsuka, UBC Pharmaceutical Support Services for the mycophenolate pregnancy registry, and Vera Therapeutics; ownership interest in Seagen; research funding from Bucksbaum Institute and Gift of Hope; honoraria from ASN for Highlights and the ASN Board Review Course; and serving in an advisory or leadership role for ASN. S.M. Moe reports consultancy agreements with Amgen, Ardelyx, and Sanifit; stock in Eli Lilly; research grants from Chugai, Keryx, and the National Institutes of Health (NIH); honoraria from Amgen, Ardelyx, and Sanifit; and serving on the editorial boards of American Journal ofNephrology and American Journal of Nutrition. M.A. Mujtaba reports honoraria from CareDx and Mallinckrodt, serving in an advisory or leadership role for Mallinckrodt, serving on the editorial board of Clinical Transplant, and speakers bureau for CareDx. R.J. Schmidt reports research funding from Arbor Research, NIH/the National Institute of Diabetes and Digestive and Kidney Diseases, and Retrophin; reports serving as the past president and a member of the board of directors of the Renal Physicians Association; and is a member of the American Association of Kidney Patients Medical Advisory Board, a member of the Kidney Transplant Collaborative Board of Directors, and a member of the Quality Insights Board of Directors. M.S. Segal reports employment with Malcom Randall Veterans Affairs Medical Center and research funding for a clinical trial with Alexion and a clinical trial with RegenMed. J.K. Tucker reports other interests or relationships as an UpToDate peer reviewer. A.C. Wiseman reports employment with Centura Transplant; consultancy agreements with CareDx, Hansa, Immucor, Meteor, Natera, Nephrosant, and Veloxis; and speakers bureau for CareDx, Sanofi Genzyme, and Veloxis. The remaining author has nothing to disclose. Funding None.
Abstract 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.
