Understanding Delayed Graft Function to Improve Organ Utilization and Patient Outcomes: Report of a Scientific Workshop Sponsored by the National Kidney Foundation.

Delayed graft function (DGF) is a common complication after kidney transplant. Despite extensive literature on the topic, the extant definition of DGF has not been conducive to advancing the scientific understanding of the influences and mechanisms contributing to its onset, duration, resolution, or long-term prognostic implications. In 2022, the National Kidney Foundation sponsored a multidisciplinary scientific workshop to comprehensively review the current state of knowledge about the diagnosis, therapy, and management of DGF and conducted a survey of relevant stakeholders on topics of clinical and regulatory interest. In this Special Report, we propose and defend a novel taxonomy for the clinical and research definitions of DGF, address key regulatory and clinical practice issues surrounding DGF, review the current state of therapies to reduce and/or attenuate DGF, offer considerations for clinical practice related to the outpatient management of DGF, and outline a prospective research and policy agenda.

Kidney Transplant Outcomes From Deceased Donors Who Received Dialysis.

Importance: Recipient outcomes after kidney transplant from deceased donors who received dialysis prior to kidney donation are not well described. Objective: To compare outcomes of transplant recipients who received kidneys from deceased donors who underwent dialysis prior to kidney donation vs recipients of kidneys from deceased donors who did not undergo dialysis. Design, Setting, and Participants: A retrospective cohort study was conducted including data from 58 US organ procurement organizations on deceased kidney donors and kidney transplant recipients. From 2010 to 2018, 805 donors who underwent dialysis prior to kidney donation were identified. The donors who underwent dialysis prior to kidney donation were matched 1:1 with donors who did not undergo dialysis using a rank-based distance matrix algorithm; 1944 kidney transplant recipients were evaluated. Exposure: Kidney transplants from deceased donors who underwent dialysis prior to kidney donation compared with kidney transplants from deceased donors who did not undergo dialysis. Main Outcomes and Measures: The 4 study outcomes were delayed graft function (defined as receipt of dialysis by the kidney recipient ≤1 week after transplant), all-cause graft failure, death-censored graft failure, and death. Results: From 2010 to 2018, 1.4% of deceased kidney donors (805 of 58 155) underwent dialysis prior to kidney donation. Of these 805 individuals, 523 (65%) donated at least 1 kidney. A total of 969 kidneys (60%) were transplanted and 641 kidneys (40%) were discarded. Among the donors with kidneys transplanted, 514 (mean age, 33 years [SD, 10.8 years]; 98 had hypertension [19.1%] and 36 had diabetes [7%]) underwent dialysis prior to donation and were matched with 514 (mean age, 33 years [SD, 10.9 years]; 98 had hypertension [19.1%] and 36 had diabetes [7%]) who did not undergo dialysis. Kidney transplants from donors who received dialysis prior to donation (n = 954 kidney recipients) were associated with a higher risk of delayed graft function compared with kidney transplants from donors who did not receive dialysis (n = 990 kidney recipients) (59.2% vs 24.6%, respectively; adjusted odds ratio, 4.17 [95% CI, 3.28-5.29]). The incidence rates did not significantly differ at a median follow-up of 34.1 months for all-cause graft failure (43.1 kidney transplants per 1000 person-years from donors who received dialysis prior to donation vs 46.9 kidney transplants per 1000 person-years from donors who did not receive dialysis; adjusted hazard ratio [HR], 0.90 [95% CI, 0.70-1.15]), for death-censored graft failure (22.5 vs 20.6 per 1000 person-years, respectively; adjusted HR, 1.18 [95% CI, 0.83-1.69]), or for death (24.6 vs 30.8 per 1000 person-years; adjusted HR, 0.76 [95% CI, 0.55-1.04]). Conclusions and Relevance: Compared with receiving a kidney from a deceased donor who did not undergo dialysis, receiving a kidney from a deceased donor who underwent dialysis prior to kidney donation was associated with a significantly higher incidence of delayed graft function, but no significant difference in graft failure or death at follow-up.

Untargeted metabolomics of perfusate and their association with hypothermic machine perfusion and allograft failure.

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.

Deceased-Donor Acute Kidney Injury and Acute Rejection in Kidney Transplant Recipients: A Multicenter Cohort.

RATIONALE & OBJECTIVE: 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. STUDY DESIGN: Prospective cohort. SETTING & PARTICIPANTS: 862 deceased donors for 1,137 kidney recipients at 13 centers. EXPOSURES: 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. OUTCOMES: 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. ANALYTICAL APPROACH: Multivariable Fine-Gray models with death as a competing risk. RESULTS: 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. LIMITATIONS: BPAR was ascertained through for-cause biopsies, not surveillance biopsies. CONCLUSIONS: 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.

Current landscape of kidney allocation: Organ procurement organization perspectives.

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

Trends in the procurement and discard of kidneys from deceased donors with acute kidney injury.

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.

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

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

COVID-19 infection in former living kidney donors.

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.

Contemporary incidence and risk factors of post transplant Erythrocytosis in deceased donor kidney transplantation.

BACKGROUND: Post-Transplant erythrocytosis (PTE) has not been studied in large recent cohorts. In this study, we evaluated the incidence, risk factors, and outcome of PTE with current transplant practices using the present World Health Organization criteria to define erythrocytosis. We also tested the hypothesis that the risk of PTE is greater with higher-quality kidneys. METHODS: We utilized the Deceased Donor Study which is an ongoing, multicenter, observational study of deceased donors and their kidney recipients that were transplanted between 2010 and 2013 across 13 centers. Eryrthocytosis is defined by hemoglobin> 16.5 g/dL in men and> 16 g/dL in women. Kidney quality is measured by Kidney Donor Profile Index (KDPI). RESULTS: Of the 1123 recipients qualified to be in this study, PTE was observed at a median of 18 months in 75 (6.6%) recipients. Compared to recipients without PTE, those with PTE were younger [mean 48±11 vs 54±13 years, p < 0.001], more likely to have polycystic kidney disease [17% vs 6%, p < 0.001], have received kidneys from younger donors [36 ±13 vs 41±15 years], and be on RAAS inhibitors [35% vs 22%, p < 0.001]. Recipients with PTE were less likely to have received kidneys from donors with hypertension [16% vs 32%, p = 0.004], diabetes [1% vs 11%, p = 0.008], and cerebrovascular event (24% vs 36%, p = 0.036). Higher KDPI was associated with decreased PTE risk [HR 0.98 (95% CI: 0.97-0.99)]. Over 60 months of follow-up, only 17 (36%) recipients had sustained PTE. There was no association between PTE and graft failure or mortality, CONCLUSIONS: The incidence of PTE was low in our study and PTE resolved in majority of patients. Lower KDPI increases risk of PTE. The underutilization of RAAS inhibitors in PTE patients raises the possibility of under-recognition of this phenomenon and should be explored in future studies.

Deceased-donor acute kidney injury is not associated with kidney allograft 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.

APOL1 Genotype and Renal Function of Black Living Donors.

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 m2; 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 m2; 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 m2 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.

Reliability of deceased-donor procurement kidney biopsy images uploaded in United Network for Organ Sharing.

Prior studies demonstrate poor agreement among pathologists' interpretation of kidney biopsy slides. Reliability of representative images of these slides uploaded to the United Network of Organ Sharing (UNOS) web portal for clinician review has not been studied. We hypothesized high agreement among pathologists' image interpretation, since static images eliminate variation induced by viewing different areas of movable slides. To test our hypothesis, we compared the assessments of UNOS-uploaded images recorded in standardized forms by three pathologists. We selected 100 image sets, each having at least two images from kidneys of deceased donors. Weighted Cohen's kappa was used for inter-rater agreement. Mean (SD) donor age was 50 (13). Acute tubular injury had kappas of 0.12, 0.14, and 0.19; arteriolar hyalinosis 0.16, 0.27, and 0.38; interstitial inflammation 0.30, 0.33, and 0.49; interstitial fibrosis 0.28, 0.32, and 0.67; arterial intimal fibrosis 0.34, 0.42, and 0.59; tubular atrophy 0.35, 0.41, and 0.52; glomeruli thrombi 0.32, 0.53, and 0.85; and global glomerulosclerosis 0.68, 0.70, and 0.77. Pathologists' agreement demonstrated kappas of 0.12 to 0.77. The lower values raise concern about the reliability of using images. Although further research is needed to understand how uploaded images are used clinically, the field may consider higher-quality standards for biopsy photomicrographs.

YKL-40 Associates with Renal Recovery in Deceased Donor Kidney Transplantation.

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<0.001) and acute tubular necrosis on procurement biopsies (P=0.05). In fully adjusted analyses, elevated donor urinary YKL-40 concentration associated with reduced risk of DGF in both recipients of AKI donor kidneys (adjusted relative risk, 0.51 [95% confidence interval (95% CI), 0.32 to 0.80] for highest versus lowest YKL-40 tertile) and recipients of non-AKI donor kidneys (adjusted relative risk, 0.79 [95% CI, 0.65 to 0.97]). Furthermore, in the event of DGF, elevated donor urinary YKL-40 concentration associated with higher 6-month eGFR (6.75 [95% CI, 1.49 to 12.02] ml/min per 1.73 m2) and lower risk of graft failure (adjusted hazard ratio, 0.50 [95% CI, 0.27 to 0.94]). These findings suggest that YKL-40 is produced in response to tubular injury and is independently associated with recovery from AKI and DGF. If ultimately validated as a prognostic biomarker, urinary YKL-40 should be considered in determining the suitability of donor kidneys for transplant.

Performance of Serum Creatinine and Kidney Injury Biomarkers for Diagnosing Histologic Acute Tubular Injury.

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.

Associations between Deceased-Donor Urine Injury Biomarkers and Kidney Transplant Outcomes.

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.

APOL1 Kidney Risk Variants and Long-Term Kidney Function in Healthy Middle-Aged Black Individuals: The Atherosclerosis Risk in Communities (ARIC) Study.

Rationale & Objective: The effect of apolipoprotein L1(APOL1) genotype on future risk of kidney disease among middle-aged individuals with good kidney function is not well established. Study Design: Longitudinal cohort study. Setting & Participants: In total, 5,886 healthy individuals (45-64 years old) enrolled in the Atherosclerosis Risk in Communities study with creatinine-based estimated glomerular filtration rate ≥ 80 mL/min who would be suitable kidney donors. Exposures: Race and APOL1 genotype. Outcomes: Creatinine- and cystatin C-based estimated glomerular filtration rate (eGFRcr-cys) using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) 2021 equation, urinary albumin-creatinine ratio (UACR), proportion with chronic kidney disease (CKD) 3a or worse, end-stage kidney disease (ESKD), and death. Analytical Approach: Participants grouped based on race and APOL1 genotype. Compared eGFRcr-cys and UACR across groups. Multinomial logistic regression models were used compare odds of CKD. Kaplan-Meier survival curves were created to compare rates of ESKD and death at last follow-up. Results: There were 5,075 Whites (86%), 701 Blacks carrying the low-risk APOL1 genotype (12%), and 110 Blacks carrying the high-risk APOL1 genotype (2%). The mean age at baseline was 53 ± 6 years. At 10 years, White participants had lower eGFRcr-cys than low-risk and high-risk groups (89 ± 16 vs 91 ± 16 and 92 ± 15 mL/min/1.73 m2, respectively; P < 0.001). At 25 years, White participants continued to have lower eGFRcr-cys than the low-risk group (70 ± 18 vs 72 ± 19 mL/min/1.73 m2; P < 0.001) but not compared with the high-risk APOL1 genotype (67±23 mL/min/1.73 m2). There was no difference in UACR among groups at 10 and 25 years (P = 0.87 and 0.91, respectively). The odds of developing CKD stage 3a or worse were not different between low-risk and high-risk APOL1 group in both unadjusted and adjusted models (P = 0.26 and P = 0.39, respectively). At last follow-up, <5% developed ESKD, and 45% of individuals either died or reached ESKD with no difference in outcomes between the groups. Limitations: Low ascertainment because of death and long follow-up. Conclusions: Among middle-aged individuals, APOL1 genotype does not appear to be a major driver of future risk of kidney disease.

Black patients with kidney disease carrying 2 variants of the apolipoprotein L1 (APOL1) gene, referred to as the high-risk genotype, experience an accelerated decline in kidney function than those with 0 or 1 risk variant. It is unknown whether the high-risk genotype negatively affects kidney function of healthy middle-aged individuals. We evaluated the effect of APOL1 genotype on kidney function of the Atherosclerosis Risk in Communities study participants (mean age 53 years) who had normal kidney function and blood pressure at baseline. At 25 years of follow-up, the APOL1 high-risk genotype did not appear to be a major driver of future risk of kidney disease. Our study findings are relevant for counseling older living donor candidates as well as family members of patients with APOL1-associated kidney disease.

Psychosocial Evaluation of Living Kidney Donors: A Survey of Current Practices in the United States.

BACKGROUND: Best practices in psychosocial evaluation and care of living donor candidates and donors are not well established. METHODS: We surveyed 195 living kidney donor (LKD) transplant centers in United States from October 2021 to April 2022 querying (1) composition of psychosocial teams, (2) evaluation processes including clinical tools and domains assessed, (3) selection criteria, and (4) psychosocial follow-up post-donation. RESULTS: We received 161 responses from 104 programs, representing 53% of active LKD programs and 67% of LKD transplant volume in 2019. Most respondents (63%) were social workers/independent living donor advocates. Over 90% of respondents indicated donor candidates with known mental health or substance use disorders were initially evaluated by the psychosocial team. Validated psychometric or transplant-specific tools were rarely utilized but domains assessed were consistent. Active suicidality, self-harm, and psychosis were considered absolute contraindications in >90% of programs. Active depression was absolute contraindication in 50% of programs; active anxiety disorder was excluded 27%. Conditions not contraindicated to donation include those in remission: anxiety (56%), depression (53%), and posttraumatic stress disorder (41%). There was acceptance of donor candidates using alcohol, tobacco, or cannabis recreationally, but not if pattern met criteria for active use disorder. Seventy-one percent of programs conducted post-donation psychosocial assessment and use local resources to support donors. CONCLUSIONS: There was variation in acceptance of donor candidates with mental health or substance use disorders. Although most programs conducted psychosocial screening post-donation, support is not standardized and unclear if adequate. Future studies are needed for consensus building among transplant centers to form guidelines for donor evaluation, acceptance, and support.