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.
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.
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.
Longitudinal cohort study.
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≥80mL/min who would be suitable kidney donors.
Race and APOL1 genotype.
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.
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.
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±15mL/min/1.73m2, respectively; P<0.001). At 25 years, White participants continued to have lower eGFRcr-cys than the low-risk group (70±18 vs 72±19mL/min/1.73m2; P<0.001) but not compared with the high-risk APOL1 genotype (67±23mL/min/1.73m2). 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.
Low ascertainment because of death and long follow-up.
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.
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.
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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.
Retrospective analysis of OPTN data from 2010 to 2020 shows increases in both the recovery and discard rates of kidneys from deceased donors with stage 3 acute kidney injury and a concurrent increase in the absolute number of transplants utilizing these kidneys.
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.
A national survey of multidisciplinary providers regarding the use of telemedicine services for living kidney donor evaluation and care delineates center practices, provider attitudes, and perceived barriers including regulatory limitations of state licensing requirements.
Delayed graft function (DGF) is a common complication of deceased donor kidney transplantation that occurs because of a complex interplay between donor organ quality and the biologic milieu of the ...recipient. The purpose of the study is to better understand the recipient risk factors leading to DGF.
We performed a retrospective cohort study using United Network for Organ sharing data and identified pairs of primary, adult kidney-only transplants that were procured from the same adult donor with discordant occurrence of DGF (i.e., one kidney of the pair had DGF).
A total of 5382 recipient pairs were analyzed. Recipients with DGF were more likely to be male (67% vs. 59%, P<0.01), African American (36% vs. 27%, P<0.01), obese (30% vs. 19%, P<0.01), diabetic (28% vs. 22%, P<0.01), on maintenance dialysis (92% vs. 83%, P<0.01), and to have longer wait-time (571 vs. 471 days, P<0.01), longer cold ischemia time (22 vs. 20 hr, P<0.01), and donor and recipient size mismatch (32% vs. 24%, P<0.01). Multivariable analyses confirmed these associations and identified panel reactive antibody more than 10% and low center volume as additional risk factors for DGF (odds ratio for panel reactive antibody >10%: 1.17, confidence interval 1.05-1.29, P<0.01; and odds ratio for <83 transplants/year: 1.29, confidence interval 1.17-1.44, P<0.01).
After fully matching for donor factors, many recipient characteristics were noted to be associated with DGF. Better management of modifiable recipient and transplant risk factors such as obesity, wait time, and cold time may help to reduce the occurrence of DGF.
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 m
) 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.
Ischemia-reperfusion injury (IRI) leading to delayed graft function (DGF), defined by the United Network for Organ Sharing as dialysis in the first week (UNOS-DGF), associates with poor kidney ...transplant outcomes. Controversies remain, however, about dialysis initiation thresholds and the utility for other criteria to denote less severe IRI, or slow graft function (SGF).
Multicenter, prospective study of deceased-donor kidney recipients to compare UNOS-DGF to a definition that combines impaired creatinine reduction in the first 48 hours or greater than 1 dialysis session for predicting 12-month estimated glomerular filtration rate (eGFR). We also assessed 10 creatinine and urine output-based SGF definitions relative to 12-month eGFR.
In 560 recipients, 215 (38%) had UNOS-DGF, 330 (59%) met the combined definition, 14 (3%) died, and 23 (4%) had death-censored graft failure by 12 months. Both DGF definitions were associated with lower adjusted 12-month eGFR (95% confidence interval)-by 7.3 (3.6-10.9) and 7.4 (3.8-11.0) mL/min per 1.73 m, respectively. Adjusted relative risks for 12-month eGFR less than 30 mL/min per 1.73 m were 1.9 (1.2-3.1) and 2.1 (1.1-3.7), with unadjusted areas under the curve of 0.618 and 0.627, respectively. For SGF definitions, postoperative day (POD) 7 creatinine had the strongest association with 12-month eGFR, and POD5 creatinine and creatinine reduction between POD1 and POD2 demonstrated modest separations in 12-month eGFR.
Although UNOS-DGF does not adequately predict 12-month function on its own, our findings do not support changing the definition. Postoperative day 7 creatinine is correlated with 12-month eGFR, but large translational studies are needed to understand the biological link between IRI severity at transplant and longer-term outcomes.
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