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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.

Kidney allocation trends from deceased donors with acute kidney injury (AKI) have not been characterized since initial Kidney Donor Profile Index reporting in 2012 and its use under the revised Kidney Allocation System (KAS) in 2014. We conducted a retrospective analysis of US registry data to characterize kidney procurement and discard trends in deceased donors with AKI, defined by ≥50% or ≥0.3 mg/dl (≥4.0 mg/dl or ≥200% for stage 3) increase in terminal serum creatinine from admission. From 2010 to 2020, 172 410 kidneys were procured from 93 341 deceased donors 16 years or older; 34 984 kidneys were discarded (17 559 from AKI donors). The proportion of stage 3 AKI donors doubled from 6% (412/6841) in 2010 to 12% (1365/11493) in 2020. Procurement of stage 3 AKI kidneys increased from 51% (423/824) to 80% (2183/2730). While discard of stage 3 AKI kidneys increased from 41% (175/423) in 2010 to 44% (960/2183) in 2020, this increase was not statistically significant in interrupted time-series analysis following KAS implementation (slope difference -0.41 [-3.22, 2.4], and level change 3.09 [-6.4, 12.6]). In conclusion, the absolute number of stage 3 AKI kidneys transplanted has increased. Ongoing high discard rates of these kidneys suggest opportunities for improved utilization.

BACKGROUND: Estimated glomerular filtration rate (eGFR) is adjusted for Black race in commonly used formulas. This has potential implications for access to simultaneous liver-kidney transplant (SLKT), as qualifying criteria rely on eGFR. METHODS: We performed a retrospective study of United Network for Organ Sharing (UNOS) national transplant registry data between 2/28/2002 and 3/31/2019 to evaluate the proportion of Black patients who would be reclassified as meeting SLKT criteria (as defined per current policies) if race adjustment were removed from two prominent eGFR equations (MDRD-4 and CKD-EPI). RESULTS: Of the 7,937 Black patients listed for transplant during the study period, we found that 3.6% would have been reclassified as qualifying for chronic kidney disease (CKD)-related SLKT with removal of race adjustment for MDRD-4, and 3.0% for CKD-EPI; this represented 23.7% and 18.7% increases in SLKT candidacy, respectively. Reclassification impacted women more than men (e.g. 4.5% vs. 3.0% by MDRD-4, p

Background and objectives Current race-based eGFR calculators assign a higher eGFR value to Black patients, which could affect the care of kidney transplant candidates and potential living donors. Design, setting, participants, & measurements We conducted a survey of staff at adult kidney transplant centers in the United States (December 17, 2020 to February 28, 2021) to assess opinions on use of race-based eGFR equations for waitlisting and living donor candidate evaluation, availability of serum cystatin C testing and measured GFR, and related practices. Results Respondents represented 57% (124 of 218) of adult kidney transplant programs, and the responding centers conducted 70% of recent kidney transplant volume. Most (93%) programs use serum creatinine-based eGFR for listing candidates. However, only 6% of respondents felt that current race-based eGFR calculators are appropriate, with desire for change grounded in concerns for promotion of health care disparities by current equations and inaccuracies in reporting of race. Most respondents (70%) believed that elimination of race would allow more preemptive waitlisting for Black patients, but a majority (79%) also raised concerns that such an approach could incur harms. More than one third of the responding programs lacked or were unsure of availability of testing for cystatin C or measured GFR. At this time, 40% of represented centers did not plan to remove race from eGFR calculators, 46% were planning to remove, and 15% had already done so. There was substantial variability in eGFR reporting and listing of multiracial patients with some Black ancestry. There was no difference in GFR acceptance thresholds for Black versus non-Black living donors. Conclusions This national survey highlights a broad consensus that extant approaches to GFR estimation are unsatisfactory, but it also identified a range of current opinions.

Although hypothermic machine perfusion (HMP) is associated with improved kidney graft viability and function, the underlying biological mechanisms are unknown. Untargeted metabolomic profiling may identify potential metabolites and pathways that can help assess allograft viability and contribute to organ preservation. Therefore, in this multicenter study, we measured all detectable metabolites in perfusate collected at the beginning and end of deceased-donor kidney perfusion and evaluated their associations with graft failure. In our cohort of 190 kidney transplants, 33 (17%) had death-censored graft failure over a median follow-up of 5.0 years (IQR 3.0-6.1 years). We identified 553 known metabolites in perfusate and characterized their experimental and biological consistency through duplicate samples and unsupervised clustering. After perfusion-time adjustment and false discovery correction, six metabolites in post-HMP perfusate were significantly associated with death-censored graft failure, including alpha-ketoglutarate, 3-carboxy-4-methyl-5-propyl-2-furanpropanoate, 1-carboxyethylphenylalanine, and three glycerol-phosphatidylcholines. All six metabolites were associated with an increased risk of graft failure (Hazard Ratio per median absolute deviation range 1.04-1.45). Four of six metabolites also demonstrated significant interaction with donation after cardiac death with notably greater risk in the donation after cardiac death group (Hazard Ratios up to 1.69). Discarded kidneys did not have significantly different levels of any death-censored graft failure-associated metabolites. On interrogation of pathway analysis, production of reactive oxygen species and increased metabolism of fatty acids were upregulated in kidneys that subsequently developed death-censored graft failure. Thus, further understanding the role of these metabolites may inform the HMP process and help improve the objective evaluation of allograft offers, thereby reducing the discard of potentially viable organs.

Background and objectives BK polyomavirus (BKV) infection commonly complicates kidney transplantation, contributing to morbidity and allograft failure. The virus is often donor-derived and influenced by ischemia-reperfusion processes and disruption of structural allograft integrity. We hypothesized that deceased-donor AKI associates with BKV infection in recipients. Design, setting, participants, & measurements We studied 1025 kidney recipients from 801 deceased donors transplanted between 2010 and 2013, at 13 academic centers. We fitted Cox proportional-hazards models for BKV DNAemia (detectable in recipient blood by clinical PCR testing) within 1 year post-transplantation, adjusting for donor AKI and other donor- and recipient-related factors. We validated findings from this prospective cohort with analyses for graft failure attributed to BKV within the Organ Procurement and Transplantation Network (OPTN) database. Results The multicenter cohort mean kidney donor profile index was 49±27%, and 26% of donors had AKI. Mean recipient age was 54±13 years, and 25% developed BKV DNAemia. Donor AKI was associated with lower risk for BKV DNAemia (adjusted hazard ratio, 0.53; 95% confidence interval, 0.36 to 0.79). In the OPTN database, 22,537 (25%) patients received donor AKI kidneys, and 272 (0.3%) developed graft failure from BKV. The adjusted hazard ratio for the outcome with donor AKI was 0.7 (95% confidence interval, 0.52 to 0.95). Conclusions In a well-characterized, multicenter cohort, contrary to our hypothesis, deceased-donor AKI independently associated with lower risk for BKV DNAemia. Within the OPTN database, donor AKI was also associated with lower risk for graft failure attributed to BKV. Podcast This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_03_10_CJN18101120_final.mp3

The coronavirus disease 2019 (COVID-19) pandemic profoundly impacted transplant services, with a particularly strong impact on living donor kidney transplantation. The COVID-19 pandemic appears to have disproportionately impacted Black patients’ access to living donor kidney transplantation. As the pandemic evolves through surges and vaccine acceptance disparities persist, ongoing attention to transplant disparities is needed.

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.

Donor acute kidney injury (AKI) activates innate immunity, enhances HLA expression in the kidney allograft, and provokes recipient alloimmune responses. We hypothesized that injury and inflammation that manifested in deceased-donor urine biomarkers would be associated with higher rates of biopsy-proven acute rejection (BPAR) and allograft failure after transplantation.Prospective cohort.862 deceased donors for 1,137 kidney recipients at 13 centers.We measured concentrations of interleukin 18 (IL-18), kidney injury molecule 1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) in deceased donor urine. We also used the Acute Kidney Injury Network (AKIN) criteria to assess donor clinical AKI.The primary outcome was a composite of BPAR and graft failure (not from death). A secondary outcome was the composite of BPAR, graft failure, and/or de novo donor-specific antibody (DSA). Outcomes were ascertained in the first posttransplant year.Multivariable Fine-Gray models with death as a competing risk.Mean recipient age was 54 ± 13 (SD) years, and 82% received antithymocyte globulin. We found no significant associations between donor urinary IL-18, KIM-1, and NGAL and the primary outcome (subdistribution hazard ratio [HR] for highest vs lowest tertile of 0.76 [95% CI, 0.45-1.28], 1.20 [95% CI, 0.69-2.07], and 1.14 [95% CI, 0.71-1.84], respectively). In secondary analyses, we detected no significant associations between clinically defined AKI and the primary outcome or between donor biomarkers and the composite outcome of BPAR, graft failure, and/or de novo DSA.BPAR was ascertained through for-cause biopsies, not surveillance biopsies.In a large cohort of kidney recipients who almost all received induction with thymoglobulin, donor injury biomarkers were associated with neither graft failure and rejection nor a secondary outcome that included de novo DSA. These findings provide some reassurance that centers can successfully manage immunological complications using deceased-donor kidneys with AKI.

There are no standardized benchmarks to measure productivity and compensation of transplant nephrologists in the United States, and consequently, criteria set for general nephrologists are often used.A web-based survey was sent to 809 nephrologists who were members of the American Society of Transplantation to gather data on measures of productivity, compensation, and job satisfaction. Factors associated with higher total compensation and job satisfaction were examined.Of 365 respondents, 260 were actively practicing in the United States and provided data on compensation. Clinical productivity was assessed variably, and although 194 (76%) had their work relative value units (wRVUs) reported to them, only 107 (44%) had an established RVU target; 234 (90%) had fixed base compensation, and 172 (66%) received a bonus on the basis of clinical workload (68%), academic productivity (31%), service (32%), and/or teaching responsibility (31%). Only 127 respondents (49%) filled out time studies, and 92 (35%) received some compensation for nonbillable transplant activity. Mean total compensation (base salary and bonus) was $274,460±$91,509. The unadjusted mean total compensation was higher with older age and was higher for men; Hispanic and White respondents; adult care transplant nephrologists; residents of the western United States; US medical school graduates; nonuniversity hospital employees; and those with an administrative title, higher academic rank, and a higher number of years in practice. Two hundred and nine respondents (80%) thought their compensation was unfair, and 180 (70%) lacked a clear understanding of how they were compensated. One hundred forty-five respondents (55%) reported being satisfied or highly satisfied with their job. Job satisfaction was greater among those with higher amounts of compensation and US medical school graduates.We report significant heterogeneity in the assessment of productivity and compensation for transplant nephrologists and the association of compensation with job satisfaction.

BACKGROUND Kidneys transplanted from deceased donors with serum creatinine-defined acute kidney injury (AKI) have similar allograft survival as non-AKI kidneys but are discarded at a higher rate. Urine injury biomarkers are sensitive markers of structural kidney damage and may more accurately predict graft outcomes. METHODS In the 2010-2013 multicenter Deceased Donor Study of 2430 kidney transplant recipients from 1298 donors, we assessed the association of donor urine injury biomarkers microalbumin, neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, IL-18, and liver-type fatty acid binding protein with graft failure (GF) and death-censored GF (dcGF) using Cox proportional hazard models (median follow-up 4 y). We examined if serum creatinine-defined donor AKI modified this association to assess the relationship between subclinical donor AKI (elevated biomarkers without creatinine-defined AKI) and GF. Through chart review of a subcohort (1137 recipients), we determined associations between donor injury biomarkers and a 3-year composite outcome of GF, mortality, or estimated glomerular filtration rate ≤ 20mL/min/1.73m. RESULTS Risk of GF, dcGF, and 3-year composite outcome did not vary with donor injury biomarker concentrations after adjusting for donor, transplant, and recipient characteristics (adjusted hazard ratio ranged from 0.96 to 1.01 per log-2 increase in biomarker). Subclinical injury in transplanted kidneys without AKI was not associated with GF. CONCLUSIONS AKI measured using injury biomarkers was not associated with posttransplant graft outcomes (at median 4 y posttransplant). When assessing posttransplant graft viability, clinicians can prioritize other donor and recipient factors over donor kidney injury, measured by either serum creatinine or urine injury biomarkers.

Living kidney donation is widely practiced throughout the world. During the past 2 decades, various groups have provided guidance about the evaluation and care of living donors. However, during this time, our knowledge in the field has advanced substantially and many agreed on the need for a comprehensive, unifying document. KDIGO (Kidney Disease: Improving Global Outcomes) addressed this issue at an international level with the publication of its clinical practice guideline on the evaluation and care of living kidney donors. The KDIGO work group extensively reviewed the available literature and wrote a series of guideline recommendations using various degrees of evidence when available. As has become recent practice, NKF-KDOQI (National Kidney Foundation-Kidney Disease Outcomes Quality Initiative) convened a work group to provide a commentary on the KDIGO guideline, with a focus on how these recommendations apply in the context of the United States. In the United States, the United Network for Organ Sharing (UNOS) guides and regulates the practice of living kidney donation. While the KDIGO guideline for the care of living kidney donors and UNOS policy are similar in most aspects of the care of living kidney donors, several important areas are not consistent or do not align with common practice by US transplantation programs in areas in which UNOS has not set specific policy. For the time being, and recognizing the value of the KDIGO guidelines, US transplantation programs should continue to follow UNOS policy.

Introduction Much of the higher risk for end-stage kidney disease (ESKD) in African American individuals relates to ancestry-specific variation in the apolipoprotein L1 gene (APOL1). Relative to kidneys from European American deceased-donors, kidneys from African American deceased-donors have shorter allograft survival and African American living-kidney donors more often develop ESKD. The National Institutes of Health (NIH)–sponsored APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO) is prospectively assessing kidney allograft survival from donors with recent African ancestry based on donor and recipient APOL1 genotypes. Methods APOLLO will evaluate outcomes from 2614 deceased kidney donor-recipient pairs, as well as additional living-kidney donor-recipient pairs and unpaired deceased-donor kidneys. Results The United Network for Organ Sharing (UNOS), Association of Organ Procurement Organizations, American Society of Transplantation, American Society for Histocompatibility and Immunogenetics, and nearly all U.S. kidney transplant programs, organ procurement organizations (OPOs), and histocompatibility laboratories are participating in this observational study. APOLLO employs a central institutional review board (cIRB) and maintains voluntary partnerships with OPOs and histocompatibility laboratories. A Community Advisory Council composed of African American individuals with a personal or family history of kidney disease has advised the NIH Project Office and Steering Committee since inception. UNOS is providing data for outcome analyses. Conclusion This article describes unique aspects of the protocol, design, and performance of APOLLO. Results will guide use of APOL1 genotypic data to improve the assessment of quality in deceased-donor kidneys and could increase numbers of transplanted kidneys, reduce rates of discard, and improve the safety of living-kidney donation., Graphical abstract

Background Acute kidney injury (AKI) in deceased donors is not associated with graft failure (GF). We hypothesize that hemodynamic AKI (hAKI) comprises the majority of donor AKI and may explain this lack of association. Methods In this ancillary analysis of the Deceased Donor Study, 428 donors with available charts were selected to identify those with and without AKI. AKI cases were classified as hAKI, intrinsic (iAKI), or mixed (mAKI) based on majority adjudication by three nephrologists. We evaluated the associations between AKI phenotypes and delayed graft function (DGF), 1-year eGFR and GF. We also evaluated differences in urine biomarkers among AKI phenotypes. Results Of the 291 (68%) donors with AKI, 106 (36%) were adjudicated as hAKI, 84 (29%) as iAKI and 101 (35%) as mAKI. Of the 856 potential kidneys, 669 were transplanted with 32% developing DGF and 5% experiencing GF. Median 1-year eGFR was 53 (IQR: 41–70) ml/min/1.73m2. Compared to non-AKI, donors with iAKI had higher odds DGF [aOR (95%CI); 4.83 (2.29, 10.22)] and had lower 1-year eGFR [adjusted B coefficient (95% CI): -11 (-19, -3) mL/min/1.73 m2]. hAKI and mAKI were not associated with DGF or 1-year eGFR. Rates of GF were not different among AKI phenotypes and non-AKI. Urine biomarkers such as NGAL, LFABP, MCP-1, YKL-40, cystatin-C and albumin were higher in iAKI. Conclusion iAKI was associated with higher DGF and lower 1-year eGFR but not with GF. Clinically phenotyped donor AKI is biologically different based on biomarkers and may help inform decisions regarding organ utilization.

BACKGROUND: De novo post-transplant diabetes mellitus (PTDM) is a common complication after kidney transplant (KT). Most recent studies are single center with various approaches to outcome ascertainment. METHODS: In a multicenter longitudinal cohort of 632 nondiabetic adult kidney recipients transplanted in 2010–2013, we ascertained outcomes through detailed chart review at 13 centers. We hypothesized that donor characteristics, such as sex, HCV infection, and kidney donor profile index (KDPI), and recipient characteristics, such as age, race, BMI, and increased HLA mismatches, would affect the development of PTDM among KT recipients. We defined PTDM as hemoglobin A1c ≥6.5%, pharmacological treatment for diabetes, or documentation of diabetes in electronic medical records. We assessed PTDM risk factors and evaluated for an independent time-updated association between PTDM and graft failure using regression. RESULTS: Mean recipient age was 52±14 years, 59% were male, 49% were Black. Cumulative PTDM incidence 5 years post-KT was 29% (186). Independent baseline PTDM risk factors included older recipient age (P

BACKGROUND Accumulating evidence implicates the complement cascade as pathogenically contributing to ischemia-reperfusion injury and delayed graft function (DGF) in human kidney transplant recipients. Building on observations that kidney injury can initiate in the donor before nephrectomy, we tested the hypothesis that anaphylatoxins C3a and C5a in donor urine before transplantation associate with risk of posttransplant injury. METHODS We evaluated the effects of C3a and C5a in donor urine on outcomes of 469 deceased donors and their corresponding 902 kidney recipients in a subset of a prospective cohort study. RESULTS We found a threefold increase of urinary C5a concentrations in donors with stage 2 and 3 acute kidney injury (AKI) compared donors without AKI (P < 0.001). Donor C5a was higher for the recipients with DGF (defined as dialysis in the first week posttransplant) compared with non-DGF (P = 0.002). In adjusted analyses, C5a remained independently associated with recipient DGF for donors without AKI (relative risk, 1.31; 95% confidence interval, 1.13-1.54). For donors with AKI, however, urinary C5a was not associated with DGF. We observed a trend toward better 12-month allograft function for kidneys from donors with C5a concentrations in the lowest tertile (P = 0.09). Urinary C3a was not associated with donor AKI, recipient DGF, or 12-month allograft function. CONCLUSIONS Urinary C5a correlates with the degree of donor AKI. In the absence of clinical donor AKI, donor urinary C5a concentrations associate with recipient DGF, providing a foundation for testing interventions aimed at preventing DGF within this high-risk patient subgroup.

The current American Society of Transplantation (AST) accredited transplant fellowship programs in the United States provide no structured formal training in leadership and administration which is essential for successfully running a transplant program. We conducted a survey of medical directors of active adult kidney and kidney-pancreas transplant programs in the United States about their demographics, training pathways, and roles and responsibilities. The survey was emailed to 183 medical directors, and 123 (67.2%) completed the survey. A majority of respondents were older than 50 years (61%), males (80%), and holding that position for more than 10 years (47%). Only 51% of current medical directors had taken that position after completing a one-year transplant fellowship, and 58% took on the role with no prior administrative or leadership experience. The medical directors reported spending a median 50%-75% of time in clinical responsibilities, 25%-50% of time in administration, and 0%-25% time in research. The survey also captured various administrative roles of medical directors vis-a-vis other transplant leaders. The study, designed to be the starting point of an improvement initiative of the AST, provided important insight into the demographics, training pathways, roles and responsibilities, job satisfaction, education needs, and training gaps of current medical directors.

The COVID‐19 pandemic brought living donor kidney transplant programs across the United States to a near halt in March 2020. As programs have begun to reopen, potential donor candidates often inquire about their risk of a COVID‐19 infection and its potential impact on kidney function after donation. To address their concerns, we surveyed 1740 former live kidney donors at four transplant centers located in New York and Michigan. Of these, 839 (48.2%) donors responded, their mean age was 46 ± 12.5 years, 543 (65%) were females, and 611 (73%) were white. Ninety‐two donors (11%) had symptoms suggestive of a COVID‐19 infection with fever (48%) and fatigue (43%) being the most common. Among those with symptoms, 42 donors underwent testing and 16 tested positive. Testing was more common among donors with private insurance, and a positive test result was more common among young black donors. Only one donor surveyed required hospitalization and none required dialysis. Fourteen donors have recovered completely and two partially. Our survey highlights that a COVID‐19 infection in former donors results in a mild disease with good recovery. These data will be useful for transplant programs to counsel living donors who are considering kidney donation during this pandemic.

Hypertension is a contributing cause of chronic kidney disease and cardiovascular morbidity and mortality. Careful assessment of blood pressure is warranted in all living kidney donor candidates via multiple office blood pressure readings and ideally also by ambulatory blood pressure monitoring. The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guideline lowered the blood pressure threshold used to define hypertension; however, the applicability of this guideline to donor acceptance remains unclear. Risk of end-stage kidney disease (ESKD) in donors is impacted by age, race, gender, blood pressure, renal function, and body mass index (BMI) at the time of donation and family history of ESKD. Therefore, thresholds for acceptable blood pressure readings vary based on each donor candidate’s specific risk profile. Young donors, especially African American males and obese individuals, merit a higher level of scrutiny due to their longer anticipated life span and/or their higher risk for kidney failure. Conversely, older non-black individuals with well-controlled hypertension using a single antihypertensive agent, who have preserved kidney function and no evidence of target organ damage, may be acceptable donor candidates. Blood pressure has been reported to increase after live kidney donation although this may be partly due to greater scrutiny and is expected with increasing age. All donors should be encouraged to participate in postdonation follow-up for blood pressure management and adopt healthy lifestyle habits.

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.

Background Deceased-donor kidneys experience extensive injury, activating adaptive and maladaptive pathways therefore impacting graft function. We evaluated urinary donor uromodulin (UMOD) and osteopontin (OPN) in recipient graft outcomes. Methods Primary outcomes: all-cause graft failure (GF) and death-censored GF (dcGF). Secondary outcomes: delayed graft function (DGF) and 6-month estimated glomerular filtration rate (eGFR). We randomly divided our cohort of deceased donors and recipients into training and test datasets. We internally validated associations between donor urine UMOD and OPN at time of procurement, with our primary outcomes. The direction of association between biomarkers and GF contrasted. Subsequently, we evaluated UMOD:OPN ratio with all outcomes. To understand these mechanisms, we examined the effect of UMOD on expression of major histocompatibility complex II in mouse macrophages. Results Doubling of UMOD increased dcGF risk (adjusted hazard ratio [aHR], 1.1; 95% confidence interval [CI], 1.02-1.2), whereas OPN decreased dcGF risk (aHR, 0.94; 95% CI, 0.88-1). UMOD:OPN ratio ≤3 strengthened the association, with reduced dcGF risk (aHR, 0.57; 0.41-0.80) with similar associations for GF, and in the test dataset. A ratio ≤3 was also associated with lower DGF (aOR, 0.73; 95% CI, 0.60-0.89) and higher 6-month eGFR (adjusted β coefficient, 3.19; 95% CI, 1.28-5.11). UMOD increased major histocompatibility complex II expression elucidating a possible mechanism behind UMOD's association with GF. Conclusions UMOD:OPN ratio ≤3 was protective, with lower risk of DGF, higher 6-month eGFR, and improved graft survival. This ratio may supplement existing strategies for evaluating kidney quality and allocation decisions regarding deceased-donor kidney transplantation.

The scope of the impact of the coronavirus disease 2019 (COVID-19) pandemic on living donor kidney transplantation (LDKT) practices is not well defined.We surveyed US transplant programs to assess practices, strategies, and barriers to living LDKT during the COVID-19 pandemic. After institutional review board approval, the survey was distributed from 9 May 2020 to 30 May 2020 by e-mail and postings to professional society list-servs. Responses were stratified based on state COVID-19 cumulative incidence levels.Staff at 118 unique centers responded, representing 61% of US living donor recovery programs and 75% of LKDT volume in the prepandemic year. Overall, 66% reported that LDKT surgery was on hold (81% in "high" vs. 49% in "low" COVID-19 cumulative incidence states). A total of 36% reported that evaluation of new donor candidates had paused, 27% reported that evaluations were very much decreased (0% to 25% typical), and 23% reported that evaluations were moderately decreased (25% to 50% typical). Barriers to LDKT surgery included program concerns for donor (85%) and recipient (75%) safety, patient concerns (56%), elective case restrictions (47%), and hospital administrative restrictions (48%). Programs with higher local COVID-19 cumulative incidence reported more barriers related to staff and resource diversion. Most centers continuing donor evaluations used remote strategies (video, 82%; telephone, 43%). As LDKT resumes, all programs will screen for COVID-19, although timeframe and modalities will vary. Recommendations for presurgical self-quarantine are also variable.The COVID-19 pandemic has had broad impacts on LDKT practice. Ongoing research and consensus building are needed to reduce barriers, to guide optimal practices, and to support safe restoration of LDKT across centers.

Background Single-center trials and retrospective case series have reported promising outcomes using kidneys from donors with hepatitis C virus (HCV) infection. However, multicenter trials are needed to determine if those findings are generalizable. Methods We conducted a prospective trial at seven centers to transplant 30 kidneys from deceased donors with HCV viremia into HCV-uninfected recipients, followed by 8 weeks of once-daily coformulated glecaprevir and pibrentasvir, targeted to start 3 days posttransplant. Key outcomes included sustained virologic response (undetectable HCV RNA 12 weeks after completing treatment with glecaprevir and pibrentasvir), adverse events, and allograft function. Results We screened 76 patients and enrolled 63 patients, of whom 30 underwent kidney transplantation from an HCV-viremic deceased donor (median kidney donor profile index, 53%) in May 2019 through October 2019. The median time between consent and transplantation of a kidney from an HCV-viremic donor was 6.3 weeks. All 30 recipients achieved a sustained virologic response. One recipient died of complications of sepsis 4 months after achieving a sustained virologic response. No severe adverse events in any patient were deemed likely related to HCV infection or treatment with glecaprevir and pibrentasvir. Three recipients developed acute cellular rejection, which was borderline in one case. Three recipients developed polyomavirus (BK) viremia near or >10,000 copies/ml that resolved after reduction of immunosuppression. All recipients had good allograft function, with a median creatinine of 1.2 mg/dl and median eGFR of 57 ml/min per 1.73 m2 at 6 months. Conclusions Our multicenter trial demonstrated safety and efficacy of transplantation of 30 HCV-viremic kidneys into HCV-negative recipients, followed by early initiation of an 8-week regimen of glecaprevir and pibrentasvir.

Black living kidney donors are at higher risk of developing kidney disease than white donors. We examined the effect of the APOL1 high-risk genotype on postdonation renal function in black living kidney donors and evaluated whether this genotype alters the association between donation and donor outcome. We grouped 136 black living kidney donors as APOL1 high-risk (two risk alleles; n =19; 14%) or low-risk (one or zero risk alleles; n =117; 86%) genotype. Predonation characteristics were similar between groups, except for lower mean±SD baseline eGFR (CKD-EPI equation) in donors with the APOL1 high-risk genotype (98±17 versus 108±20 ml/min per 1.73 m 2 ; P =0.04). At a median of 12 years after donation, donors with the APOL1 high-risk genotype had lower eGFR (57±18 versus 67±15 ml/min per 1.73 m 2 ; P =0.02) and faster decline in eGFR after adjusting for predonation eGFR (1.19; 95% confidence interval, 0 to 2.3 versus 0.4; 95% confidence interval, 0.1 to 0.7 ml/min per 1.73 m 2 per year, P =0.02). Two donors developed ESRD; both carried the APOL1 high-risk genotype. In a subgroup of 115 donors matched to 115 nondonors by APOL1 genotype, we did not find a difference between groups in the rate of eGFR decline ( P =0.39) or any statistical interaction by APOL1 status ( P =0.92). In conclusion, APOL1 high-risk genotype in black living kidney donors associated with greater decline in postdonation kidney function. Trajectory of renal function was similar between donors and nondonors. The association between APOL1 high-risk genotype and poor renal outcomes in kidney donors requires validation in a larger study.

Introduction Existing methods to predict recipient allograft function during deceased-donor kidney procurement are imprecise. Understanding the potential renal reparative role for monocyte chemoattractant protein-1 (MCP-1), a cytokine involved in macrophage recruitment after injury, might help to predict allograft outcomes. Methods We conducted a substudy of the multicenter prospective Deceased Donor Study cohort that evaluated deceased kidney donors from 5 organ procurement organizations from May 2010 to December 2013. We measured urine MCP-1 (uMCP-1) concentrations from donor samples collected at nephrectomy to determine associations with donor acute kidney injury (AKI), recipient delayed graft function (DGF), 6-month estimated glomerular filtration rate (eGFR), and graft failure. We also assessed perfusate MCP-1 concentrations from pumped kidneys for associations with DGF and 6-month eGFR. Results AKI occurred in 111 donors (9%). The median (interquartile range) uMCP-1 concentration was higher in donors with AKI compared with donors without AKI (1.35 [0.41–3.93] ng/ml vs. 0.32 [0.11–0.80] ng/ml, P < 0.001). DGF occurred in 756 recipients (31%), but uMCP-1 was not independently associated with DGF. Higher donor uMCP-1 concentrations were independently associated with a higher 6-month eGFR in those without DGF (0.77 [0.10–1.45] ml/min per 1.73 m2 per doubling of uMCP1). However, there were no independent associations between uMCP-1 and graft failure over a median follow-up of ∼2 years. Lastly, perfusate MCP-1 concentrations significantly increased during pump perfusion but were not associated with DGF or 6-month eGFR. Discussion Donor uMCP-1 concentrations were modestly associated with higher recipient 6-month eGFR in those without DGF. However, the results suggest that donor uMCP-1 has minimal clinical utility given no associations with graft failure.

Deceased-donor acute kidney injury (AKI) is associated with organ discard and delayed graft function, but data on longer-term allograft survival are limited. We performed a multicenter study to determine associations between donor AKI (from none to severe based on AKI Network stages) and all-cause graft failure, adjusting for donor, transplant, and recipient factors. We examined whether any of the following factors modified the relationship between donor AKI and graft survival: kidney donor profile index, cold ischemia time, donation after cardiac death, expanded-criteria donation, kidney machine perfusion, donor-recipient gender combinations, or delayed graft function. We also evaluated the association between donor AKI and a 3-year composite outcome of all-cause graft failure or estimated glomerular filtration rate ≤ 20 mL/min/1.73 m2 in a subcohort of 30% of recipients. Among 2,430 kidneys transplanted from 1,298 deceased donors, 585 (24%) were from donors with AKI. Over a median follow-up of 4.0 years, there were no significant differences in graft survival by donor AKI stage. We found no evidence that pre-specified variables modified the effect of donor AKI on graft survival. In the subcohort, donor AKI was not associated with the 3-year composite outcome. Donor AKI was not associated with graft failure in this well-phenotyped cohort. Given the organ shortage, the transplant community should consider measures to increase utilization of kidneys from deceased donors with AKI.

Survival for patients with multiple myeloma has significantly improved in the last decade in large part due to the development of proteasome inhibitors and immunomodulatory drugs. These next generation agents with novel mechanisms of action as well as targeted therapies are being used both in the preclinical and clinical settings for patients with myeloma. These agents include monoclonal antibodies, deacetylase inhibitors, kinase inhibitors, agents affecting various signaling pathways, immune check point inhibitors, and other targeted therapies. In some cases, off target effects of these therapies can lead to unanticipated effects on the kidney that can range from electrolyte disorders to AKI. In this review, we discuss the nephrotoxicities of novel agents currently in practice as well as in development for the treatment of myeloma.

Disorders of plasma and B cells leading to paraproteinemias are associated with a variety of renal diseases. Understanding the mechanisms of injury and associated nephropathies provides a framework that aids clinicians in prompt diagnosis and appropriate adjunctive treatment of these disorders. Glomerular diseases that may be associated with paraproteinemias include amyloid deposition, monoclonal Ig deposition disease, proliferative GN with monoclonal Ig deposits, C3 glomerulopathy caused by alterations in the complement pathway, immunotactoid glomerulopathy, fibrillary GN, and cryoglobulinemia. Tubular lesions include the classic Fanconi syndrome, light–chain proximal tubulopathy, interstitial fibrosis, and cast nephropathy. These paraproteinemic renal diseases are distinct in their pathogenesis as well as their urinary and kidney biopsy findings. Renal pathology is usually initiated by deposition and direct involvement of the intact monoclonal Ig or Ig fragments with resident cells of the nephron. Our review summarizes current insights into the underlying molecular pathogenesis of these interesting kidney lesions.

Deceased donor kidneys with AKI are often discarded for fear of poor transplant outcomes. Donor biomarkers that predict post-transplant renal recovery could improve organ selection and reduce discard. We tested whether higher levels of donor urinary YKL-40, a repair phase protein, associate with improved recipient outcomes in a prospective cohort study involving deceased kidney donors from five organ procurement organizations. We measured urinary YKL-40 concentration in 1301 donors (111 had AKI, defined as doubling of serum creatinine) and ascertained outcomes in the corresponding 2435 recipients, 756 of whom experienced delayed graft function (DGF). Donors with AKI had higher urinary YKL-40 concentration (P

Background. Efforts to maximize transplantation by matching organ quality to recipient longevity require reliable tools. The US kidney allocation system uses the Kidney Donor Risk Index (KDRI) for this purpose, and many centers additionally rely on donor biopsies. The Leuven score combines donor age with procurement histology (glomerulosclerosis and interstitial fibrosis/tubular atrophy) to predict allograft survival. Methods. We compared KDRI with Leuven scores for associations with kidney discard, delayed graft function, and allograft function and survival. We used Cox, modified Poisson, and linear regression to calculate risks based on KDRI and (separately) Leuven scores, adjusting for important transplant and recipient variables. Results. From 890 donors, 1729 kidneys were procured and biopsied. Five hundred eighty-five (34%) kidneys were discarded. Median donor age was 53 years (interquartile range [IQR], 44-61 years). Median KDRI and Leuven scores were 1.56 (IQR, 1.28-1.90) and 59 (IQR, 49-69). Relative risk for discard was 1.21 (95% confidence interval [CI], 1.17-1.24) per 0.2-unit increase in KDRI and 1.38 (1.31-1.46) per 10-unit increase in Leuven score. Adjusted relative risks for delayed graft function were 0.98 (95% CI, 0.94-1.02) and 0.94 (95% CI, 0.90-0.99), adjusted hazard ratios for graft failure were 1.10 (95% CI, 1.04-1.16) and 1.11 (95% CI, 1.02-1.21), and adjusted linear regression coefficients for 3-year estimated glomerular filtration rate were −3.88 (−4.63 to −3.13) and -5.18 (−6.19 to −4.18). Conclusions. In kidneys clinically selected for procurement biopsy, the Leuven score was more strongly associated with discard but performed similarly to KDRI for predicting transplant outcomes, suggesting the need to reevaluate current procurement biopsy practices. Given modest associations for both tools; however, neither KDRI nor the Leuven score should be used in isolation for individual organ acceptance decisions.

Assessment of deceased-donor organ quality is integral to transplant allocation practices, but tools to more precisely measure donor kidney injury and better predict outcomes are needed. In this study, we assessed associations between injury biomarkers in deceased-donor urine and the following outcomes: donor AKI (stage 2 or greater), recipient delayed graft function (defined as dialysis in first week post-transplant), and recipient 6-month eGFR. We measured urinary concentrations of microalbumin, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), IL-18, and liver-type fatty acid binding protein (L-FABP) from 1304 deceased donors at organ procurement, among whom 112 (9%) had AKI. Each biomarker strongly associated with AKI in adjusted analyses. Among 2441 kidney transplant recipients, 31% experienced delayed graft function, and mean±SD 6-month eGFR was 55.7±23.5 ml/min per 1.73 m(2) In analyses adjusted for donor and recipient characteristics, higher donor urinary NGAL concentrations associated with recipient delayed graft function (highest versus lowest NGAL tertile relative risk, 1.21; 95% confidence interval, 1.02 to 1.43). Linear regression analyses of 6-month recipient renal function demonstrated that higher urinary NGAL and L-FABP concentrations associated with slightly lower 6-month eGFR only among recipients without delayed graft function. In summary, donor urine injury biomarkers strongly associate with donor AKI but provide limited value in predicting delayed graft function or early allograft function after transplant.

Sickle cell nephropathy (SCN) is associated with iron/heme deposition in proximal renal tubules and related acute tubular injury (ATI). Here we report the utility of iron staining in differentiating causes of renal allograft dysfunction in patients with a history of sickle cell disease. Case 1: the patient developed acute allograft dysfunction two years after renal transplant. Her renal biopsy showed ATI, supported by patchy loss of brush border and positive staining of kidney injury molecule-1 in proximal tubular epithelial cells, where diffuse increase in iron staining (2+) was present. This indicated that ATI likely resulted from iron/heme toxicity to proximal tubules. Electron microscope confirmed aggregated sickle RBCs in glomeruli, indicating a recurrent SCN. Case 2: four years after renal transplant, the patient developed acute allograft dysfunction and became positive for serum donor-specific antibody. His renal biopsy revealed thrombotic microangiopathy (TMA) and diffuse positive C4d stain in peritubular capillaries. Iron staining was negative in the renal tubules, implying that TMA was likely associated with acute antibody-mediated rejection (AAMR, type 2) rather than recurrent SCN. These case reports imply that iron staining is an inexpensive but effective method in distinguishing SCN-associated renal injury in allograft kidney from other etiologies.

Renal transplant recipients are prone to develop drug toxicities because of polypharmacy and drug-drug interactions. Colchicine is often used for the treatment of gout in these patients as nonsteroidal medications are contraindicated. In addition, patients are often on corticosteroids and frequent, periodic, dose escalation for gouty flare may lead to side effects. Colchicine-induced myopathy has been very well described in the literature. Several cases of colchicine toxicity have been reported in cyclosporine-treated patients due to a drug-drug interaction. We report a 62-year-old African American renal transplant recipient who had been doing well on tacrolimus-based immunosuppression and was started on colchicine (0.6 mg twice daily) for gouty flare. A few days later, he was found to have a 4-fold increase in aspartate aminotransferase and an elevated creatine phosphokinase. Although this interaction is very well known with cyclosporine, it has not yet been reported in patients on tacrolimus.

Kidneys with “high” Kidney Donor Profile Index (KDPI) are often biopsied and pumped, yet frequently discarded. In this multicenter study, we describe the characteristics and outcomes of kidneys with KDPI of 80 or greater that were procured from 338 deceased donors. We excluded donors with anatomical kidney abnormalities. Donors were categorized by the number of kidneys discarded: (1) none (n = 154, 46%), (2) 1 discarded and 1 transplanted (n = 48, 14%), (3) both discarded (n = 136, 40%). Donors in group 3 were older, more often white, and had higher terminal creatinine and KDPI than group 1 (all P < 0.05). Biopsy was performed in 92% of all kidneys, and 47% were pumped. Discard was associated with biopsy findings and first hour renal resistance. Kidney injury biomarker levels (neutrophil gelatinase-associated lipocalin, IL-18, and kidney injury molecule-1 measured from donor urine at procurement and from perfusate soon after pump perfusion) were not different between groups. There was no significant difference in 1-year estimated glomerular filtration rate or graft failure between groups 1 and 2 (41.5 ± 18 vs 41.4 ± 22 mL/min per 1.73 m2; P = 0.97 and 9% vs 10%; P = 0.76). Kidneys with KDPI of 80 or greater comprise the most resource consuming fraction of our donor kidney pool and have the highest rates of discard. Our data suggest that some discarded kidneys with KDPI of 80 or greater are viable; however, current tools and urine and perfusate biomarkers to identify these viable kidneys are not satisfactory. We need better methods to assess viability of kidneys with high KDPI.

Background The diagnosis of acute kidney injury (AKI), which is currently defined as an increase in serum creatinine (Scr) concentration, provides little information on the condition's actual cause. To improve phenotyping of AKI, many urinary biomarkers of tubular injury are being investigated. Because AKI cases are not frequently biopsied, the diagnostic accuracy of concentrations of Scr and urinary biomarkers for histologic acute tubular injury is unknown. Study Design Cross-sectional analysis from multicenter prospective cohort. Settings & Participants Hospitalized deceased kidney donors on whom kidney biopsies were performed at the time of organ procurement for histologic evaluation. Predictors (1) AKI diagnosed by change in Scr concentration during donor hospitalization and (2) concentrations of urinary biomarkers (neutrophil gelatinase-associated lipocalin [NGAL], liver-type fatty acid-binding protein [L-FABP], interleukin 18 [IL-18], and kidney injury molecule 1 [KIM-1]) measured at organ procurement. Outcome Histologic acute tubular injury. Results Of 581 donors, 98 (17%) had mild acute tubular injury and 57 (10%) had severe acute tubular injury. Overall, Scr-based AKI had poor diagnostic performance for identifying histologic acute tubular injury and 49% of donors with severe acute tubular injury did not have AKI. The area under the receiver operating characteristic curve (AUROC) of change in Scr concentration for diagnosing severe acute tubular injury was 0.58 (95% CI, 0.49-0.67) and for any acute tubular injury was 0.52 (95% CI, 0.45-0.58). Compared with Scr concentration, NGAL concentration demonstrated higher AUROC for diagnosing both severe acute tubular injury (0.67; 95% CI, 0.60-0.74; P=0.03) and any acute tubular injury (0.60; 95% CI, 0.55-0.66; P=0.005). In donors who did not have Scr-based AKI, NGAL concentrations were higher with increasing severities of acute tubular injury (subclinical AKI). However, compared with Scr concentration, AUROCs for acute tubular injury diagnosis were not significantly higher for urinary L-FABP, IL-18, or KIM-1. Limitations The spectrum of AKI cause in deceased donors may be different from that of a general hospitalized population. Conclusions Concentrations of Scr and kidney injury biomarkers (L-FABP, IL-18, and KIM-1) lack accuracy for diagnosing acute tubular injury in hospitalized deceased donors. Although urinary NGAL concentration had slightly higher discrimination for acute tubular injury than did Scr concentration, its overall AUROC was still modest.

Accurate and reliable assessment tools are needed in transplantation. The objective of this prospective, multicenter study was to determine the associations of the alpha and pi iso-enzymes of glutathione S-transferase (GST), measured from perfusate solution at the start and end (base and post) of kidney allograft machine perfusion, with subsequent delayed graft function (DGF). We also compared GST iso-enzyme perfusate levels from discarded versus transplanted kidneys. A total of 428 kidneys were linked to outcomes as recorded by the United Network of Organ Sharing. DGF, defined as any dialysis in the first week of transplant, occurred in 141 recipients (32%). Alpha and pi-GST levels significantly increased during machine perfusion. The adjusted relative risks (95% confidence interval) of DGF with each log-unit increase in base and post pi-GST were 1.14 (1.0-1.28) and 1.33 (1.02-1.72), respectively. Alpha-GST was not independently associated with DGF. There were no significant differences in GST values between discarded and transplanted kidneys, though renal resistance was significantly higher in discarded kidneys. We found pi-GST at the end of machine perfusion to be independently associated with DGF. Further studies should elucidate the utility of GST for identifying injured kidneys with regard to organ allocation, discard and recipient management decisions.

Background and objectives The influence of deceased-donor AKI on post-transplant outcomes is poorly understood. The few published studies about deceased-donor preimplant biopsy have reported conflicting results regarding associations between AKI and recipient outcomes. Design, setting, participants, & measurements This multicenter study aimed to evaluate associations between deceased-donor biopsy reports of acute tubular necrosis (ATN) and delayed graft function (DGF), and secondarily for death-censored graft failure, first adjusting for the kidney donor risk index and then stratifying by donation after cardiac death (DCD) status. Results Between March 2010 and April 2012, 651 kidneys (369 donors, 4 organ procurement organizations) were biopsied and subsequently transplanted, with ATN reported in 110 (17%). There were 262 recipients (40%) who experienced DGF and 38 (6%) who experienced graft failure. DGF occurred in 45% of kidneys with reported ATN compared with 39% without ATN ( P =0.31) resulting in a relative risk (RR) of 1.13 (95% confidence interval [95% CI], 0.9 to 1.43) and a kidney donor risk index–adjusted RR of 1.11 (95% CI, 0.88 to 1.41). There was no significant difference in graft failure for kidneys with versus without ATN (8% versus 5%). In stratified analyses, the adjusted RR for DGF with ATN was 0.97 (95% CI, 0.7 to 1.34) for non-DCD kidneys and 1.59 (95% CI, 1.23 to 2.06) for DCD kidneys ( P =0.02 for the interaction between ATN and DCD on the development of DGF). Conclusions Despite a modest association with DGF for DCD kidneys, this study reveals no significant associations overall between preimplant biopsy-reported ATN and the outcomes of DGF or graft failure. The potential benefit of more rigorous ATN reporting is unclear, but these findings provide little evidence to suggest that current ATN reports are useful for predicting graft outcomes or deciding to accept or reject allograft offers.