Joanna C. Dionne1,2,3Patricia Campbell4Héloïse Cardinal5,6Tatiana Giannidis1Aviva Goldberg7
S. Joseph Kim8,9Greg Knoll10Michel Pâquet6Christina Parsons11Yuhong Yuan3
Rahul Mainra12*- 1Department of Medicine, McMaster University, Hamilton, ON, Canada
- 2Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada
- 3Division of Gastroenterology, McMaster University, Hamilton, ON, Canada
- 4Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada
- 5Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montreal, QC, Canada
- 6Division of Nephrology, Centre Hospitalier de l’Université de Montréal, Montreal, QC, Canada
- 7Department of Pediatrics and Child Health, University of Manitoba Max Rady College of Medicine, Winnipeg, MB, Canada
- 8Division of Nephrology, Department of Medicine, University of Toronto, Toronto, ON, Canada
- 9Ajmera Transplant Centre, University Health Network, Toronto, ON, Canada
- 10Division of Nephrology, Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ottawa, ON, Canada
- 11Canadian Blood Services, Ottawa, ON, Canada
- 12Division of Nephrology, Department of Medicine, University of Saskatchewan, Saskatoon, SK, Canada
Underutilization of deceased donor organs has worsened the gap in the number of kidneys available for transplantation. The purpose of this clinical practice guideline is to provide recommendations on the utilization of donor kidneys at risk of discard. Six conditional recommendations were made all with very low certainty of evidence: 1) We suggest utilizing extended criteria donor (ECD) kidneys for transplantation rather than remaining on the wait list and continuing with dialysis; 2) We suggest utilizing kidneys from ECD versus non-ECD in selected transplant candidates; 3) We suggest that organs from older kidney donors can be used in selected transplant candidates who may derive benefit from them; 4) We suggest that kidneys from deceased donors with acute kidney injury can be used for transplantation based on clinician assessment and donor factors; 5) We suggest that donor kidneys with acute kidney injury from either ECD or non-ECD be used for kidney transplantation; 6) We suggest using kidneys from donors after death determination by circulatory criteria for transplantation. This clinical practice guideline provides evidence for the use of deceased donor kidneys that are at risk of discard and may improve the shared decision-making between transplant physicians and wait-listed patients.
Introduction
Kidney transplantation remains the preferred treatment for patients with end stage kidney disease (ESKD), leading to improved life expectancy and quality of life when compared to remaining on dialysis [1, 2]. Unfortunately, there is a gap in the supply and demand for transplantable organs. Exacerbating this gap is the underutilization of deceased donor kidneys, reported to be as high as 20% of donated kidneys [3]. Meanwhile, patients die while awaiting this lifesaving gift. Despite the availability of compatible deceased donor kidneys, physicians may decline offers on behalf of their patients with the main concern being around kidney quality. These decisions lead to longer wait times, waitlist removal and sometimes death for patients awaiting transplantation [4].
In 2019, Canadian Blood Services convened a Steering Committee of transplant nephrologists, surgeons, and representatives from organ donation organizations (ODOs) to discuss the concern of potential organ (kidney) underutilization in Canada. One main priority identified by this group was to examine the current literature and perform a systematic review to guide evidence-based decision-making at the time of a deceased organ donor offer.
Kidneys at risk of underutilization are generally those with acute kidney injury (AKI), from older donor age, extended criteria donor (ECD) or with high Kidney Donor Risk Index (KDRI). Extended criteria donors are deceased donors aged 60 and above or 50–59 with at least 2 of the following characteristics: history of hypertension, stroke as cause of death or terminal serum creatinine above 132 μmol/L. In a seminal 2002 publication, transplantations of kidneys from ECD were associated with a risk (hazard ratio) of graft loss defined as death, return to dialysis or re-transplantation above 1.7 [5]. The KDRI is a score including donor variables which has been derived from a large retrospective cohort study including all first kidney transplant recipients in the US between 1995 and 2005 [6]. This score is associated with the risk of graft loss and can be expressed as the kidney donor profile index (KDPI), which is the percentile of a donor’s KDRI in the distribution of all donor KDRIs of a reference year. KDPI values are hence comprised between 0% and 100%, with higher values indicating a higher risk of graft loss.
Therefore, we present recommendations on common clinical questions that physicians face when making decisions to accept or decline kidneys that are at risk of discard.
Materials and Methods
The Steering Committee
A steering committee (SC) was formed to address optimizing the use of extended criteria deceased organ donors in kidney transplantation. The SC included experts in paediatric and adult transplant nephrology, surgery, ethics and guideline methodology.
Sponsorship
This guideline was supported and endorsed by Canadian Blood Services.
Question Development
Priority questions were developed in PICO (Population, Intervention, Comparison and Outcome) format to address evidence for use of extended criteria donor kidneys including, age, presence of acute kidney injury, and donation after death determination by circulatory criteria (DCC, also known as DCD or donation following circulatory death) compared to donation after death determination by neurologic criteria (DNC, also known as NDD or neurological death determination). Questions were developed with the steering committee via teleconferences. Outcomes were then identified and voted upon using an anonymous online voting website. Outcomes were rated as critical [7–9], important [4–6], or limited important [1–3] [7]. Each committee member voted on the outcomes using a modified Delphi approach. Critical outcomes included: mortality, graft survival, graft failure (patient death and graft failure requiring re-transplant or return to dialysis), and quality of life. Important outcomes included: rejection, readmission to hospital, DGF, estimated glomerular filtration rate (eGFR) at 1 year and 3 years, hospital length of stay, infection risk, and malignancy risk.
Search Strategy and Screening
A search strategy was developed by a medical librarian. We searched MEDLINE, EMBASE, and Cochrane from inception until April 2024. The search strategy also underwent peer review from a second medical librarian. Search terms included: kidney transplant, renal transplant, extended criteria, ECD, acute kidney failure, acute kidney injury, kidney donor, age, infection, neurologic determination of death and donation after cardiac death. The results from the search were uploaded into COVIDENCE [8]. Four reviewers (JCD, YY, CP, TG) screened results for clinical trials, observational studies, and systematic reviews for relevant citations. Title, abstract and full text screening were done in duplicate (JCD, YY, TG). Any disagreement about inclusion at the full text stage was resolved through consensus.
Data Extraction and Risk of Bias Assessment
Systematic reviews were conducted for each of the PICO questions. Using a standardised pilot data extraction form, the methodology team (JCD, YY, TG) performed data extraction and risk of bias assessment, which in turn were verified by a second reviewer. For clinical trials, the Cochrane Risk of Bias tool 2.0 [9] was used. For observational studies, the Newcastle-Ottawa Risk of Bias [10] assessment tool was employed.
Data Analysis
For PICO questions that had sufficient data for analysis, a meta-analysis was performed using RevMan version 5.4 [11]. For all outcomes, we calculated fixed and random effects estimates. For PICO questions with less than five studies, we utilised a fixed effects model. For most PICO questions, a random effects model was used. For dichotomous outcomes, we reported a relative risk (RR) or odds ratios (OR). For continuous variables, a mean difference (MD) was used. All effect size measures are reported with 95% confidence intervals (CI). For PICO questions where there was insufficient data to allow for meta-analysis, the evidence was synthesised narratively.
The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) process [12]. In accordance with GRADE, we rated the certainty of evidence for each outcome as high, moderate, low or very low [13]. We rated the certainty of evidence for each outcome as high if data were from randomized controlled trials (RCTs) and low if data were from observational studies. The data were rated down 1 or 2 levels if the results were at serious, or very serious risk of bias, if there were serious inconsistencies across studies, if the evidence was indirect, or if there were concerns regarding publication bias. Data were rated up in observational studies if there were large effect sizes or dose-response gradients.
Evidence Summary and Recommendation Formulation
Evidence summaries for each of the PICO questions (Supplementary Material S1) were developed by the methodologists (JCD, YY) including information on the methodology of each study, population, interventions, pooled estimates for each outcome, and overall rating of the certainty of evidence. Evidence to decision (EtD) frameworks (Supplementary Material S2) were completed by the SC to draft recommendations considering certainty of the evidence, balance of desirable and undesirable effects, resources required, feasibility, acceptability, and equity. Recommendations were considered approved if at least 80% of the committee agreed with the statement.
Guidelines
Part 1: The Evidence for the Use of Extended Criteria Donor Kidneys
Recommendation 1: We Suggest Utilizing ECD Kidneys for Transplantation Rather than Remaining on the Wait List and Continuing with Dialysis (Conditional Recommendation, Very Low Certainty of Evidence)
Evidence Summary
Transplantation with kidneys from ECD are associated with a lower risk of mortality (pooled RR 0.88, 95% CI 0.84, 0.92) [14, 15] when compared with remaining on dialysis.
Justification
Although kidneys from ECD are associated with a moderately higher risk of graft loss than those from non-ECD, the decision to accept or decline such kidneys must be made by comparing the benefits and risks of transplantation versus remaining on dialysis waiting for a better offer. Our systematic review of the literature and meta-analysis show that transplantation with kidneys from ECD is associated with lower mortality than remaining on dialysis (pooled RR 0.88, 95% CI 0.84, 0.92) [14, 15]. In the largest study supporting this result, the survival benefit was seen in recipients aged more than 40, especially in areas with long wait times [14].
Due to heterogeneity in KDPI categories and outcomes in relevant studies, we could not perform a meta-analysis of the data expressing transplant outcomes according to donor KDPI. Nevertheless, we identified one large retrospective cohort study which provided results similar to those presented in our systematic review for ECD. This study showed that accepting a kidney from a donor with high KDPI was associated with a survival benefit compared with remaining on dialysis [16].
The quality of evidence is very low as a result of the high risk of bias given the retrospective nature of the studies and the inconsistencies in results between studies.
Implementation
Kidneys from ECD are already utilized in clinical practice. Implementation considerations include identifying ways to operationalize wider utilization, promote transplant physician and candidate education as to the survival benefit of transplantation with kidneys from ECD to improve shared decision-making when kidneys from ECD are offered.
Research Priorities
Impact of transplantation with kidneys from ECD on cost effectiveness of the procedure and quality of life of kidney transplant candidates and recipients are needed. A provider preferences survey including conjoint analysis with transplant recipients could help determine the elements driving decision-making for accepting or declining kidneys from ECD. Better data are needed to determine which patients are the best candidates to receive ECD kidneys and efforts should be made to implement more consistent practices across the country.
Recommendation 2: We Suggest Utilizing Kidneys from ECD Versus Non-ECD in Selected Transplant Candidates (Conditional Recommendation, Very Low Certainty of Evidence)
Evidence Summary
Transplantation with kidneys from ECD versus non-ECD is associated with a moderately increased risk of mortality [14, 17–28], graft loss, DGF, and a small decrease in death-censored graft survival. There were no differences in the incidence of acute rejection, and hospital readmissions in transplantations performed with kidneys from ECD versus non-ECD.
Justification
Our systematic review of the literature and meta-analysis indicate that the risk of mortality (pooled RR 1.5, 95% CI 1.25, 1.80) [17–19, 21–26, 28–36], graft loss (pooled RR 1.63, 95% CI 1.32, 2.02) [18, 27, 28, 35, 37–39] and DGF (pooled RR 1.23, 95% CI 1.04, 1.46 [17–19, 21–26, 31, 35, 37–70] were moderately increased when transplantation was performed with kidneys from ECD versus non-ECD, while death-censored graft survival was only mildly improved when non-ECD were transplanted as compared with ECD (pooled RR 0.95, 95% CI 0.90, 0.99) [14, 26, 36, 42, 64–66, 71]. The risk of acute rejection (pooled RR 1.10, 95% CI 0.89, 1.37) [17–19, 21–24, 26, 31, 32, 35, 37–41, 45, 46, 48, 50, 52, 53, 55–57, 61, 63, 65, 66, 72–77] and hospital readmission (pooled RR 1.17, 95% CI 0.71, 1.92) [32, 37, 38, 62, 66, 67, 76] were not different when transplantation with kidneys from ECD was compared with transplantation with kidneys from non-ECD.
We performed a literature search to identify transplant outcomes by donor quality when the latter was expressed as the KDPI. Due to heterogeneity in KDPI cut-offs that define risk donor categories across studies, we were unable to perform a meta-analysis on the data. Nevertheless, the results of studies comparing transplantations with kidneys from donors with high versus low KDPI were similar to those comparing outcomes of transplantation in patients receiving ECD versus non-ECD. Transplantation with kidneys from donors with high KDPI reported a higher risk of graft loss and DGF compared with kidneys from donors with lower KDPI values.
The quality of the evidence was very low due to limitations in study design (observational studies only), the risk of selection and confounding biases due to differences in recipient characteristics among those who get offered kidneys from ECD, and double counting across studies using similar databases.
Implementation
Kidneys from ECD are already utilized in clinical practice. Implementation considerations are similar to Recommendation 1, Part 1. Ultimately identifying patients that will benefit from accepting an ECD kidney transplant compared to remaining on dialysis is imperative in wider utilization.
Research Priorities
Studies that address the barriers and facilitators that promote wider utilization should be performed, as well as studies that evaluate the impacts of using more ECD on cost-effectiveness and quality of life of transplant candidates and recipients. Research is also required to better understand which potential transplant candidates will benefit the most from these kidneys vs. remaining on dialysis.
Recommendation 3: We Suggest that Organs from Older Kidney Donors Can be Used in Selected Transplant Candidates Who May Derive Benefit from them (Conditional Recommendation, Very Low Certainty of Evidence).
Evidence Summary
The data supporting the recommendations were derived from non-randomised (i.e., observational) studies. The studies span the spectrum in scope, ranging from single centre reports to large national registry analyses. In addition, follow-up varied across studies from 1, 3, 5, to 10 years. Most studies dichotomized “younger” vs. “older” deceased donors as < 65 years vs. >/ = 65 years. It was acknowledged by the panel that age cut-offs used in these analyses are somewhat arbitrary, but 65 years of age seemed to be a widely adopted threshold for categorising the deceased donor population.
The pooled data showed that kidneys from younger (vs. older) deceased donors were generally associated with a higher relative likelihood of patient survival (RR 0.95, 95% CI: 0.93, 0.98) [21, 56, 78–97] and graft survival (RR 0.88, 95% CI: 0.86, 0.91) [21, 56, 78–80, 82–85, 87–89, 92, 98–113]. Furthermore, recipients of kidneys from older donors were more likely to experience DGF (RR 1.29, 95% CI: 1.12, 1.48) [78, 80–84, 86, 87, 89–92, 97, 98, 111, 113–124] and acute rejection (RR 1.18, 95% CI: 1.02, 1.37) [78, 82, 83, 90, 92, 96, 98, 99, 107, 115, 119, 122, 123, 125] when compared to recipients of kidneys from younger donors. Despite these differences, it was noted by the panel members that these differences were relatively small and other outcomes such as death-censored graft survival were comparable across the two groups (RR 0.97, 95% CI: 0.94, 1.00) [21, 78, 82, 84, 86, 87, 90–92, 94, 97, 117, 122].
The overall certainty of the evidence was very low given that the estimates were derived from comparisons in donor age groups with varying degrees of control for confounding and selection biases. Variation in the application of age cut-offs and the decision to dichotomize a continuous variable such as donor age to facilitate presentation of the results may have led to measurement bias.
Justification
Although the comparison of recipient outcomes between kidney transplanted from younger vs. older donors favoured younger donors in various domains (including graft survival), it was highlighted by the panel members that the net benefit of using kidneys from older donors in appropriate recipient candidates may provide substantial benefit at a system level in light of their broad availability, the continued mismatch between supply and demand for organs, and the relatively small differences in recipient outcomes between kidney transplants from younger vs. older donors. It is notable that the certainty of the evidence is very low given the risk for bias in the outcome estimates from observational studies.
The included studies provided no information on the cost-effectiveness of different strategies for using younger vs. older donor kidneys nor did they explicitly address issues of equity. Given that kidneys from a wide spectrum of donor ages are already being used in clinical practice, the panel felt that developing strategies to optimise the use of older donor kidneys would be both acceptable and feasible.
Implementation
The panel highlighted that donor age is a continuum and thus implementation of policies around the use of these kidneys should consider the impact of extremes of age on recipient outcomes. Other implementation considerations include defining the best approach to operationalizing the use of kidneys from a wider age spectrum, including the integration of shared decision-making frameworks that account of patient and provider preferences.
Research Priorities
One main research priority is being able to identify which recipients will benefit from transplantation with older donor kidneys. Future studies should establish the quality of life of recipients receiving older vs. younger donor kidneys. Furthermore, it would be important to establish the cost-effectiveness of strategy that expands the use of kidneys from older donors. Research on ways to modify and improve the function as well as long-term outcomes of older donor kidneys should be a priority. These studies may include interventions on donors and/or recipients as well as the rational application of biomarkers in supporting the management of the organ and patient.
Part 2: The Evidence for the Use of Kidneys With Acute Kidney Injury
Recommendation 1: We Suggest that Kidneys from Deceased Donors with AKI Can be Used for Transplantation Based on Clinician Assessment and Donor Factors (Conditional Recommendation, Very Low Certainty of Evidence).
Evidence Summary
For the comparison of outcomes of renal transplantation using kidneys from deceased donors who had an acute kidney injury vs. deceased donors who did not (non-AKI), only observational studies were included in the analysis. Thereby, the risk of bias is high. Outcomes that were analysed included mortality and graft survival at different time points, and acute rejection up to a year. Graft survival at 1 year in 12 observational studies including over 16,000 patients was lower in donors with AKI: (RR 1.14, 95% CI: 1.02, 1.27) [22, 26, 35, 126–134]. No difference was found in graft loss at 3 years (RR 1.03, 95% CI: 0.84, 1.26) [56, 127, 128]. Mortality was similar at varying time points from 1 to 6 years (RR 0.80, 95% CI: 0.56, 1.14) [26, 35, 56, 127, 131–137]. No significant difference was found in the rate of DGF when the deceased donor had AKI (RR 1.53, 95% CI: 0.88, 2.68) [26, 35, 50, 53, 127–129, 131–154], and little to no difference was found in the rate of acute rejection up to 1 year after transplant as a function of deceased donor AKI status (RR 1.02, 95% CI: 0.94, 1.11) [26, 53, 127, 131–134, 138–142, 144, 149, 150, 152, 155].
Justification
No worrisome signal was seen in outcomes from kidneys whose donor had AKI. In particular, there was no difference in graft survival up to 10 years post-transplant, no difference in mortality up to 5 years and no difference in acute rejection at 1 year. Therefore, we suggest that kidneys from donors with AKI can be used for transplantation. However, this is based on very low certainty of evidence. Of note, severity of AKI (stage 1, 2 or 3) or the need for renal replacement therapy in deceased donors was not considered in these observational studies. Moreover, the studies could only ascertain the outcomes of AKI kidneys that were transplanted. The factors distinguishing AKI kidneys that were declined vs. used (and the outcomes of the former if they did get used for transplantation) are not clear. Having said this, using kidneys from deceased donors with AKI is both feasible and acceptable under the appropriate settings.
Implementation
The relative effect of using kidneys from deceased donors with AKI on graft loss is trivial. These kidneys are already being used by some transplant programs, but more widespread use should be encouraged. Implementation of the widespread use of donors with AKI will require improved education of accepting physicians on the positive outcomes of these specific kidneys. Furthermore, awareness of critical care and donor physicians that such kidneys may be donated is needed. Although not universal, some physicians do request a reassuring biopsy prior to accepting these organs. Resources to increase access of timely renal biopsy results may also be required, however this was not studied by our group.
Research Priorities
The very low certainty of evidence points to a research priority assessing the efficacy and the safety of using kidneys from deceased donors with AKI for kidney transplantation. Such future multicentre studies should use a standardised definition of AKI, stage of AKI, cause of AKI, and whether donor kidney replacement therapy was needed. Outcomes in different transplant candidate subgroups might identify specific transplant candidates who would benefit most from these kidneys.
Recommendation 2: We Suggest that Donor Kidneys with AKI from Either ECD or Non-ECD be Used for Kidney Transplantation (Weak Recommendation, Very Low Certainty of Evidence)
Evidence Summary
A total of six observational studies were found in the literature [22, 26, 50, 53, 126, 137]. The definition of AKI was not standardized and varied from between studies. Overall, there was no statistically significant differences in any of the outcomes of interest between donor kidneys with AKI labelled as ECD or non-ECD. There was a small difference in overall graft survival with a RR 1.1 (95% CI 1.0–1.2) favouring non-ECD kidneys with AKI [26, 53, 55]. However, there was no difference in mortality [22, 26, 134], DGF [22, 26, 50, 53, 134, 137], acute rejection [26, 50, 53, 135, 137] or eGFR [22, 26, 50, 53] at 1 year.
Justification
The available studies suggest that donors with AKI have similar outcomes regardless of ECD or non-ECD status. Given the lack of standardization of AKI definition and the uncertainty around the use of renal biopsy prior to transplantation, this is a weak recommendation. The outcome measures do not suggest any significant harm from transplanting kidneys from ECD with AKI. It is therefore feasible that this category of donor kidneys can be transplanted safely in selected recipients. None of the studies discussed cost utilization given the potential for DGF, although the data did not suggest a higher risk in ECD with AKI.
Implementation
It is possible that ECD with AKI make up a large proportion of underutilized organs. Appropriate use of these organs can lead to increased access to transplantation for selected patients with ESKD. Improving knowledge and education along with shared decision making between clinicians and patients is important to consider in the implementation of this strategy. Other implementation concerns are highlighted in Recommendation 1, Part 2.
Research Priorities
The evidence guiding this recommendation is of very low certainty and there is opportunity to inform the transplant community with well-designed studies using a standardized definition of AKI. Biopsy practices vary and additional research could focus on biopsy results and transplant outcomes. Other research questions are mentioned in Recommendation 1, Part 2.
Part 3: The Evidence for the Use of Kidneys From Donors After Circulatory and Neurologic Determination of Death
Recommendation 1: We suggest Using Kidneys from Donors After Death Determination by Circulatory Criteria for Transplantation (Conditional Recommendation, Very Low Certainty of Evidence)
Evidence Summary
The literature comparing recipient outcomes of kidneys transplanted from donors after DNC vs. DCC are based on observational studies from single-centre, multicentre, and national data sources. There are no randomised controlled trials that have established the comparative effectiveness of these two approaches. DCC kidney transplants have seen a resurgence over the last 20 years due to advances in surgical recovery techniques, organ preservation, and the continued gap between the supply and demand for transplantable organs.
The evidence synthesis showed that recipients of DCC kidneys experienced a higher risk of all-cause mortality (RR 1.33, 95% CI: 1.15, 1.54) [156–164] and graft loss (RR 1.08, 95% CI: 1.00, 1.17) [158–161, 163–165] when compared to recipients of DNC kidneys. The relative likelihood of death-censored graft loss was comparable between the two groups (RR 1.04, 95% CI: 0.92, 1.17) [159, 162]. Recipients of DCC kidney transplants had an 89% increase in the risk of DGF when compared to those who received a DNC kidney transplant (RR 1.89, 95% CI: 1.80, 1.99) [19, 156, 158, 160, 162, 163, 166–169]. Although the point estimate for acute rejection suggested a 62% increased risk among DCC (vs. DNC) kidney recipients, the level of precision did not allow for definitive conclusions (RR 1.62, 95% CI: 0.77, 3.42) [19, 157, 160, 163, 167, 169, 170].
Similar to other analyses that compare recipient outcomes across specific donor characteristics, the overall certainty of the evidence was very low due to the estimates being derived from comparisons that vary in terms of bias control for confounding and selection. The inclusion of studies derived from the same data sources (e.g., national registry) may lead to double counting of subjects and events, leading to measurement bias.
Justification
There was a moderately desirable effect of DNC over DCC kidney transplants, particularly in the domains of mortality and delayed graft function. DCC kidney transplants clearly had a notably higher relative likelihood of DGF, which is consistent with the mechanism of donation (i.e., longer warm ischemia time in DCC than DNC). Of note, differences in graft loss and acute rejection were null or trivial. This supports the recommendation to explore ways to increase the use DCC kidneys, when available, in patient groups that may benefit from them.
Implementation
DCC kidney transplants are being used in many organ donation and transplantation systems across the world but there may be opportunities to expand their deployment in certain countries, regions, and jurisdictions. One must also consider the resources/costs associated with properly undertaking life-support discontinuation, donor monitoring, and rapid preservation/recovery of organs after cessation of circulation in the donor. DCC kidney recipients are almost two-fold more likely to experience DGF, which has implications of inpatient dialysis services and length of stay.
Research Priorities
Reliable methods to predict death following discontinuation of life-support will support the rational allocation of resources to optimise the availability of DCC organs for transplantation. Moreover, research on ways to safely extend the time from withdrawal of life-sustaining therapies until death and techniques to improve organ viability (with reductions in DGF rates) should be prioritised.
Discussion
Organ utilization is a primary concern for a wide spectrum of healthcare users, providers, and payers. Kidney transplantation provides patients with an improved quality of life and overall life expectancy compared to remaining on dialysis and is the preferred treatment for ESKD. Not only is there clinical benefit for patients, but transplantation leads to considerable cost savings [171, 172]. Kidney underutilization exacerbates the organ shortage problem facing patients with ESKD, increasing wait times, and reducing access to transplantation. Furthermore, the public may lose trust in the organ donation and transplant systems if utilization of this precious gift is not optimized.
Clinicians are faced with the difficult decision of accepting or declining a kidney that is non-standard criteria. This clinical practice guideline summarizes the available evidence on the outcomes of non-standard criteria donor kidneys, labelled as either ECD, older age, DCC or those with AKI. We present the recommendations of six PICOs that may assist in clinical decision making. There was ample evidence in the literature, however given the limitations of the data, only conditional recommendations could be provided for all PICOs. The nature of retrospective, registry data with the potential for double-counting leads to the potential for bias, which limits the strength of these recommendations.
It is important to appreciate that the results of all these studies includes kidneys that were ultimately transplanted. There are likely many kidneys that are not transplanted which outcomes are unknown. One could assume that if all kidneys were transplanted, outcomes may be worse with non-standard criteria donor kidneys. However, we are not advocating that all kidneys are transplanted but appropriate clinical decision making to identify those that will provide patients with improved outcomes. We feel confident that our data are inclusive of all relevant literature up to April of 2024. We undertook rigorous methodological assessments following well established GRADE criteria to determine the strength of the data. Lastly, our steering committee did not have a patient partner that was guiding our PICO question development and determination of outcomes that are important to patients. However, we do believe that these are important questions that carry importance to our patients.
Overall, the majority of studies show small or trivial differences in outcomes of importance when transplanting a kidney from an older donor, ECD, DCC or those donors suffering AKI. Although some studies revealed the potential for poorer outcomes, we believe the limitations of the data call to question these results. Ultimately this decision must balance the risk of potential negative outcomes to the benefit of improved life expectancy and quality of life with a transplant compared to remaining on dialysis.
A recent study published after our search was complete present a systematic review of the literature on the outcomes of kidney transplantation from donors with AKI. Overall, their results were in concordance with ours when investigating specifically donors with AKI and graft outcomes. They do present a few studies that highlighted the impact of AKIN stages on graft outcomes. Only stage 3 AKI portended a poorer prognosis with higher rates of DGF, but this did not lead to worse long term graft outcomes. They also highlighted the differences in the aetiology of AKI and its impact on graft outcomes comparing hemodynamic, intrinsic and mixed causes. Only intrinsic AKI resulted in higher rates of DGF and a lower 1-year eGFR [173].
This guideline is only one component in our attempts to improved kidney utilization. The importance of patient knowledge and education cannot be understated. Patients awaiting transplantation must have easy to understand education provided in a time of low stress, in other words not at the time of an organ offer. Prior work from our group has confirmed this and suggested that most elderly patients are willing to accept a kidney transplant with reduced long-term outcomes to provide them freedom from dialysis for 3–5 years [174]. Identifying the right recipient for the right kidney can lead to improved patient outcomes and improved organ utilization. Ultimately as we transplant more kidneys that are at risk of underutilization, we must accept as a community the potential for reduced long-term outcomes. Individual programs that are focused on performance indicators such as long-term graft survival may have to shift their priority to other markers of success. Furthermore, the utilization of non-standard kidneys into an ever-increasing complex patient population may also lead to higher healthcare needs and the financial costs associated with it. To address this adequately, high quality prospective research is required.
There are other clinical factors which have an impact on organ underutilization. There is robust evidence that hypothermic machine perfusion (HMP) reduces the risk of DGF in deceased donor kidney transplantation [175]. Graft survival was also improved with the use of HMP in some but not all studies. An interesting pharmacoeconomic analysis proposed that the use of HMP for ECD kidneys led to an improvement in utilization with a higher number of transplants. Overall costs were higher but in their proposed scenario of HMP for ECD kidneys and static cold storage for SCD kidneys, there were cost savings realized on the fifth year [176]. Other reports also document the potential for a lower discard rate with the use of HMP [177, 178]. Despite the limited evidence that histological findings on recovered deceased donor kidneys is associated with graft outcomes, procurement biopsy for ECD kidneys is a common practice [179]. There is a strong association between biopsy findings and organ discard rate with the degree of glomerulosclerosis (>20%) and macroscopic arteriosclerosis being important histological findings affecting decision making [180, 181]. If procurement biopsies are a common practice for ECD kidneys to assist with decision making, utilizing standardized clinical pathological scores may improve utilization. Zhang and colleagues developed a kidney donor quality score (KDQS) based on deep learning assessment of procurement biopsies [182]. The KDQS in addition to clinical covariates predicted one- and five-year graft loss with an area under the curve of 0.70 and 0.64, respectively, and thus has the potential to reduce kidney discards. Lastly, dual kidney transplantation may improve utilization of ECD kidneys that would otherwise be discarded. Donor kidneys that are at risk of discard based on histological or clinical criteria can be successfully transplanted using an algorithm decision tree [183]. High risk donors based on clinical and histological criteria underwent dual kidney transplantation resulting in similar graft survival as single kidney transplantation from similar donors but lower biopsy lesions.
We highlight several research priorities and unmet needs in this topic. Further research is required to determine cost effectiveness of this strategy, patient quality of life, and more accurate ways of identifying characteristics of recipients and donor kidneys to improve overall outcomes. This clinical guideline has the potential to increase kidney utilization reducing the gap of organ shortage for patients with ESKD.
Data Availability Statement
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.
Ethics Statement
Ethical approval was not required for the study involving humans in accordance with the local legislation and institutional requirements. Written informed consent to participate in this study was not required from the participants or the participants’ legal guardians/next of kin in accordance with the national legislation and the institutional requirements.
Author Contributions
JD: Participated in research design, data analysis, performance of the research, writing of the paper. PC: Participated in research design, performance of the research, writing of the paper. HC: Participated in research design, performance of the research, writing of the paper. TG: Participated in research design, data analysis, performance of the research. AG: Participated in research design, performance of the research, writing of the paper. SK: Participated in research design, performance of the research, writing of the paper. GK: Participated in research design, performance of the research, writing of the paper. MP: Participated in research design, performance of the research, writing of the paper. CP: Participated in research design, performance of the research. YY: Participated in research design, data analysis, performance of the research. RM: Participated in research design, performance of the research, writing of the paper. All authors contributed to the article and approved the submitted version.
Funding
The author(s) declare that financial support was received for the research and/or publication of this article. The authors declare that this study received funding from Canadian Blood Services. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.
Conflict of Interest
PC is retired and no longer works at University of Alberta. CP no longer works with Canadian Blood Services. This work was presented as an abstract at the Canadian Society of Transplant Annual Scientific Meeting, October 2024.
The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Generative AI Statement
The author(s) declare that no Generative AI was used in the creation of this manuscript.
Supplementary Material
The Supplementary Material for this article can be found online at: https://www.frontierspartnerships.org/articles/10.3389/ti.2025.14596/full#supplementary-material
Abbreviations
AKI, acute kidney injury; AKIN, acute kidney injury network; CI, confidence interval; DCC, death determination by circulatory criteria; DCD, donation following circulatory death; DGF, delayed graft function; DNC, death determination by neurological criteria; ECD, extended criteria donor; eGFR, estimated glomerular filtration rate; ESKD, end stage kidney disease; EtD, evidence to decision; GRADE, Grading of Recommendations, Assessment, Development and Evaluation; HMP, hypothermic machine perfusion; KDPI, kidney donor profile index; KDQS, kidney donor quality score; KDRI, kidney donor risk index; NDD, neurological death determination; ODO, organ donation organizations; OR, odds ratio; MD, mean difference; PICO, Population, Intervention, Comparison and Outcome; RCTs, randomized controlled trials; RR, relative risk; SC, steering committee.
References
1. Wolfe, RA, Ashby, VB, Milford, EL, Ojo, AO, Ettenger, RE, Agodoa, LY, et al. Comparison of Mortality in All Patients on Dialysis, Patients on Dialysis Awaiting Transplantation, and Recipients of a First Cadaveric Transplant. N Engl J Med (1999) 341(23):1725–30. doi:10.1056/NEJM199912023412303
2. Laupacis, A, Keown, P, Pus, N, Krueger, H, Ferguson, B, Wong, C, et al. A Study of the Quality of Life and Cost-Utility of Renal Transplantation. Kidney Int (1996) 50(1):235–42. doi:10.1038/ki.1996.307
3. Hart, A, Smith, JM, Skeans, MA, Gustafson, SK, Wilk, AR, Castro, S, et al. OPTN/SRTR 2018 Annual Data Report: Kidney. Am J Transpl (2020) 20(Suppl. s1):20–130. doi:10.1111/ajt.15672
4. Husain, SA, King, KL, Pastan, S, Patzer, RE, Cohen, DJ, Radhakrishnan, J, et al. Association between Declined Offers of Deceased Donor Kidney Allograft and Outcomes in Kidney Transplant Candidates. JAMA Netw Open (2019) 2(8):e1910312. doi:10.1001/jamanetworkopen.2019.10312
5. Port, FK, Bragg-Gresham, JL, Metzger, RA, Dykstra, DM, Gillespie, BW, Young, EW, et al. Donor Characteristics Associated with Reduced Graft Survival: An Approach to Expanding the Pool of Kidney Donors. Transplantation (2002) 74(9):1281–6. doi:10.1097/00007890-200211150-00014
6. Rao, PS, Schaubel, DE, Guidinger, MK, Andreoni, KA, Wolfe, RA, Merion, RM, et al. A Comprehensive Risk Quantification Score for Deceased Donor Kidneys: The Kidney Donor Risk Index. Transplantation (2009) 88(2):231–6. doi:10.1097/TP.0b013e3181ac620b
7. Schünemann, HBJ. GRADE Handbook for Grading Quality of Evidence and Strength of Recommendations (2013).
8. Veritas Health Innovation. Covidence Systematic Review Software. Melbourne, Australia (2019). (Covidence systematic review software).
9. Sterne, JAC, Savović, J, Page, MJ, Elbers, RG, Blencowe, NS, Boutron, I, et al. RoB 2: A Revised Tool for Assessing Risk of Bias in Randomised Trials. BMJ (2019) 366:l4898. doi:10.1136/bmj.l4898
10. Peterson, J. The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-Analyses (2011).
11. The Cochrane Collaboration. Review Manager. Version 5.4. Copenhagen: The Nordic Cochrane Centre (2014).
12. Guyatt, GH, Oxman, AD, Vist, GE, Kunz, R, Falck-Ytter, Y, Alonso-Coello, P, et al. GRADE: An Emerging Consensus on Rating Quality of Evidence and Strength of Recommendations. BMJ (2008) 336(7650):924–6. doi:10.1136/bmj.39489.470347.AD
13. Guyatt, GH, Oxman, AD, Vist, G, Kunz, R, Brozek, J, Alonso-Coello, P, et al. GRADE Guidelines: 4. Rating the Quality of Evidence--Study Limitations (Risk of Bias). J Clin Epidemiol (2011) 64(4):407–15. doi:10.1016/j.jclinepi.2010.07.017
14. Merion, RM, Ashby, VB, Wolfe, RA, Distant, DA, Hulbert-Shearon, TE, Metzger, RA, et al. Deceased-Donor Characteristics and the Survival Benefit of Kidney Transplantation. JAMA (2005) 294(21):2726–33. doi:10.1001/jama.294.21.2726
15. Martin Navarro, J, Ortega, M, Gutierrez, MJ, Garcia Martin, F, Alcazar, JM, Morales, JM, et al. Survival of Patients Older Than 60 Years with Kidneys Transplanted from Spanish Expanded Criteria Donors versus Patients Continued on Hemodialysis. Transplant Proc (2009) 41(6):2376–8. doi:10.1016/j.transproceed.2009.06.176
16. Massie, AB, Luo, X, Chow, EKH, Alejo, JL, Desai, NM, and Segev, DL. Survival Benefit of Primary Deceased Donor Transplantation with High-KDPI Kidneys. Am J Transpl (2014) 14(10):2310–6. doi:10.1111/ajt.12830
17. Aubert, O, Vernerey, D, Empana, JP, Kamar, N, Rostaing, L, Viglietti, D, et al. Long Term Outcomes of Transplantation Using Kidneys from Expanded Criteria Donors: Prospective, Population Based Cohort Study. BMJ (Online) (2015) 351:h3557. doi:10.1136/bmj.h3557
18. Barba, J, Zudaire, JJ, Robles, JE, Rosell, D, Berian, JM, and Pascual, I. Complications of Kidney Transplantation with Grafts from Expanded Criteria Donors. World J Urol (2013) 31(4):893–900. doi:10.1007/s00345-012-0831-3
19. Bell, R, Farid, S, Upasani, V, Ahmad, N, Pandanaboyana, S, and Baker, R. The Evolution of Donation after Circulatory Death Renal Transplantation: A Decade of Experience. Nephrol Dial Transplant (2019) 34(10):1788–98. doi:10.1093/ndt/gfy160
20. Domagala, P, Kwiatkowski, A, Wszola, M, Cybula, K, Chmura, A, Trzebicki, J, et al. Complications of Transplantation of Kidneys from Expanded-Criteria Donors. Transplant Proc (2009) 41(8):2970–1. doi:10.1016/j.transproceed.2009.07.085
21. Ferreira, E, Costa, J, Romaozinho, C, Santos, L, Macario, F, Alves, R, et al. Long-Term Outcomes of Kidney Transplantation from Expanded-Criteria Deceased Donors: A Single-Center Experience. Transplant Proc (2017) 49(4):770–6. doi:10.1016/j.transproceed.2017.01.051
22. Jung, D, Park, S, Kim, SH, Eom, M, Kim, JS, Yang, JW, et al. Decision Making by Young Transplant Surgeons Regarding Expanded-Criteria Donors with Acute Kidney Injury or Allocation Failure. Transplant Proc (2016) 48(3):695–700. doi:10.1016/j.transproceed.2015.11.025
23. Keitel, E, Michelon, T, dos Santos, AF, Bittar, AE, Goldani, JC, D’Almeida Bianco, P, et al. Renal Transplants Using Expanded Cadaver Donor Criteria. Ann Transplant : Q Polish Transplant Soc (2004) 9(2):23–4.
24. Khan, SM, Moritz, MJ, Saeed, MI, Kumar, A, Jaglan, S, Heifets, M, et al. Successful Transplantation of Kidneys from Deceased Donors with Acute Renal Failure: Three-Year Results. Transplantation (2006) 82(12):1640–5. doi:10.1097/01.tp.0000250908.62948.8f
25. Kim, BS, Joo, SH, Ahn, HJ, Choi, JH, Park, HC, and Lee, SH. Outcomes of Expanded-Criteria Deceased Donor Kidney Transplantation in a Single Center. Transplant Proc (2014) 46(4):1067–70. doi:10.1016/j.transproceed.2013.12.014
26. Klein, R, Galante, NZ, de Sandes-Freitas, TV, de Franco, MF, Tedesco-Silva, H, and Medina-Pestana, JO. Transplantation with Kidneys Retrieved from Deceased Donors with Acute Renal Failure. Transplantation (2013) 95(4):611–6. doi:10.1097/TP.0b013e318279153c
27. Lee, KW, Park, JB, Cha, SR, Lee, SH, Chung, YJ, Yoo, H, et al. Dual Kidney Transplantation Offers a Safe and Effective Way to Use Kidneys from Deceased Donors Older Than 70 Years. BMC Nephrol (2020) 21(1):3. doi:10.1186/s12882-019-1664-8
28. Singh, RP, Farney, AC, Rogers, J, Zuckerman, J, Reeves-Daniel, A, Hartmann, E, et al. Kidney Transplantation from Donation after Cardiac Death Donors: Lack of Impact of Delayed Graft Function on Post-Transplant Outcomes. Clin Transplant (2011) 25(2):255–64. doi:10.1111/j.1399-0012.2010.01241.x
29. Al-Shraideh, Y, Stratta, R, Farney, A, Orlando, G, Palanisamy, A, Reeves-Daniel, A, et al. Primary Non Function after Deceased Donor Kidney Transplantation: Risks and Consequences. Abstract# D2484 Transplant (2014) 98:631. doi:10.1097/00007890-201407151-02136
30. Domagala, P, Kwiatkowski, A, Wszola, M, Panufnik, L, Chmura, A, Perkowska-Ptasinska, A, et al. Assessment of Kidneys Procured from Expanded Criteria Donors before Transplantation. Transplant Proc (2009) 41(8):2966–9. doi:10.1016/j.transproceed.2009.08.004
31. Lee, CM, Carter, JT, Randall, HB, Hiose, R, Stock, PG, Melzer, JS, et al. The Effect of Age and Prolonged Cold Ischemia Times on the National Allocation of Cadaveric Renal Allografts. J Surg Res (2000) 91(1):83–8. doi:10.1006/jsre.2000.5921
32. Moore, PS, Farney, AC, Rogers, J, Gautreaux, MD, Hairston, G, Stratta, RJ, et al. Experience with Deceased Donor Kidney Transplantation in 114 Patients Over Age 60. Surgery (2007) 142(4):514–23.e5232. doi:10.1016/j.surg.2007.08.005
33. Ojo, AO, Hanson, JA, Meier-Kriesche, HU, Okechukwu, CN, Wolfe, RA, Leichtman, AB, et al. Survival in Recipients of Marginal Cadaveric Donor Kidneys Compared with Other Recipients and Wait-Listed Transplant Candidates. J Am Soc Nephrol (2001) 12(3):589–97. doi:10.1681/ASN.V123589
34. Alexander, JW, Whiting, JF, Golconda, M, First, MR, Smith, R, and O’Brien, S. Economic Costs of Expanded Criteria Donors in Renal Transplantation. Transplantation (1998) 65(2):204–7. doi:10.1097/00007890-199801270-00010
35. Wiwattanathum, P, Ingsathit, A, Kantachuvesiri, S, Arpornsujaritkun, N, Tirapanich, W, and Sumethkul, V. Stabilization of Estimated Glomerular Filtration Rate in Kidney Transplantation from Deceased Donors with Acute Kidney Injuries. World J Transplant (2016) 6(4):712–8. doi:10.5500/wjt.v6.i4.712
36. Rigotti, P, Capovilla, G, Di Bella, C, Silvestre, C, Donato, P, Baldan, N, et al. A Single-Center Experience with 200 Dual Kidney Transplantations. Clin Transpl (2014) 28(12):1433–40. doi:10.1111/ctr.12475
37. Bonsignore, P, Pagano, D, Piazza, S, Ricotta, C, di Francesco, F, Cintorino, D, et al. Crucial Role of Extended Criteria Donors in Deceased Donor Single Kidney Transplantation to Face Chronic Shortage in the Heart of the Mediterranean Basin: A Single-Center Experience. Transplant Proc (2019) 51(9):2868–72. doi:10.1016/j.transproceed.2019.02.075
38. Farney, AC, Singh, RP, Rogers, J, Gautreaux, MD, Stratta, RJ, Hines, MH, et al. Experience in Renal and Extrarenal Transplantation with Donation after Cardiac Death Donors with Selective Use of Extracorporeal Support. J Am Coll Surgeons (2008) 206(5):1028–37. doi:10.1016/j.jamcollsurg.2007.12.029
39. Nakamura, Y, Kihara, Y, Yokoyama, T, Konno, O, and Iwamoto, H. Similar Outcomes of Kidney Transplantations Using Organs from Donors after Cardiac Death and Donors after Brain Death. Transplant Proc (2018) 50(8):2404–11. doi:10.1016/j.transproceed.2018.03.088
40. Serwanska-Swietek, M, Wszola, M, Domagala, P, Berman, A, Bieniasz, M, Kieszek, R, et al. Analysis of Distribution of Expanded- and Standard-Criteria Donors and Complications Among Polish Recipients by Kidney Donor Risk Index Value. Transplant Proc (2018) 50(6):1686–90. doi:10.1016/j.transproceed.2018.02.132
41. Zadori, G, Kovacs, DA, Fedor, R, Kanyari, Z, Zsom, L, Asztalos, L, et al. Results of Expanded-Criteria Donor Kidneys: A Single-Center Experience in Hungary. Transplant Proc (2015) 47(7):2189–91. doi:10.1016/j.transproceed.2015.07.023
42. Al-Shraideh, Y, Farooq, U, Farney, AC, Palanisamy, A, Rogers, J, Orlando, G, et al. Influence of Recipient Age on Deceased Donor Kidney Transplant Outcomes in the Expanded Criteria Donor Era. Clin Transpl (2014) 28(12):1372–82. doi:10.1111/ctr.12463
43. Balaz, P, Rokosny, S, Wohlfahrtova, M, Viklicky, O, Wohlfahrt, P, Bartonova, A, et al. Identification of Expanded-Criteria Donor Kidney Grafts at Lower Risk of Delayed Graft Function. Transplantation (2013) 96(7):633–8. doi:10.1097/TP.0b013e31829d9225
44. Cardinal, H, Lamarche, F, Grondin, S, Marsolais, P, Lagace, AM, Duca, A, et al. Organ Donor Management and Delayed Graft Function in Kidney Transplant Recipients: A Multicenter Retrospective Cohort Study. Am J Transplant (2019) 19(1):277–84. doi:10.1111/ajt.15127
45. Farney, AC, Al-Geizawi, S, Rogers, J, Stratta, RJ, and Hines, MH. Lessons Learned from a Single Center’s Experience with 134 Donation after Cardiac Death Donor Kidney Transplants. J Am Coll Surgeons (2011) 212(4):440–51. doi:10.1016/j.jamcollsurg.2010.12.033
46. Ferrer, F, Mota, A, Alves, R, Bastos, C, Macario, F, Figueiredo, A, et al. Renal Transplantation with Expanded Criteria Donors: The Experience of One Portuguese Center. Transplant Proc (2009) 41(3):791–3. doi:10.1016/j.transproceed.2009.02.044
47. Frutos, MA, Mansilla, JJ, Ruiz, P, Seller, G, Sola, E, and Martin-Gomez, A. Expanded Criteria Donors for Kidney Transplantation: Quality Control and Results. Transplant Proc (2006) 38(8):2371–3. doi:10.1016/j.transproceed.2006.08.035
48. Goplani, KR, Kute, VB, Vanikar, AV, Shah, PR, Gumber, MR, Patel, HV, et al. Expanded Criteria Donor Kidneys for Younger Recipients: Acceptable Outcomes. Transplant Proc (2010) 42(10):3931–4. doi:10.1016/j.transproceed.2010.09.040
49. Han, M, Jeon, HJ, Ryu, HJ, Jeong, JC, Koo, TY, Kwon, HY, et al. Kidney Donor Risk Index Is a Good Prognostic Tool for Graft Outcomes in Deceased Donor Kidney Transplantation with Short, Cold Ischemic Time. Clin Transplant (2014) 28(3):337–44. doi:10.1111/ctr.12318
50. Heilman, RL, Huskey, J, Chakkera, HA, Khamash, H, Smith, ML, Kurian, SM, et al. Transplanting Kidneys from Deceased Donors with Severe Acute Kidney Injury. Am J Transplant (2015) 15(8):2143–51. doi:10.1111/ajt.13260
51. Helantera, I, Ibrahim, HN, Lempinen, M, and Finne, P. Donor Age, Cold Ischemia Time, and Delayed Graft Function. Clin J Am Soc Nephrol : CJASN (2020) 15(6):813–21. doi:10.2215/CJN.13711119
52. Hwang, JK, Park, SC, Kim, JI, Kwon, KH, Moon, IS, Choi, BS, et al. Long-Term Outcomes of Kidney Transplantation from Expanded Criteria Deceased Donors at a Single Center: Comparison with Standard Criteria Deceased Donors. Transplant Proc (2014) 46(2):431–6. doi:10.1016/j.transproceed.2013.11.061
53. Jacobi, J, Rebhan, D, Heller, K, Velden, J, Hilgers, KF, Wullich, B, et al. Donor Acute Kidney Injury and Short-Term Graft Outcome in Renal Transplantation. Clin Transplant (2014) 28(10):1131–41. doi:10.1111/ctr.12425
54. Kim, SM, Ahn, S, Min, SI, Park, D, Park, T, Min, SK, et al. Cold Ischemic Time Is Critical in Outcomes of Expanded Criteria Donor Renal Transplantation. Clin Transplant (2013) 27(1):132–9. doi:10.1111/ctr.12034
55. Ko, KJ, Kim, YH, Kwon, KH, Kim, MH, Park, SC, Yun, SS, et al. Kidney Transplantation Using Expanded-Criteria Deceased Donors: A Comparison with Ideal Deceased Donors and Non-Expanded-Criteria Deceased Donors. Transplant Proc (2018) 50(10):3222–7. doi:10.1016/j.transproceed.2018.05.028
56. Kumar, MS, Panigrahi, D, Dezii, CM, Abouna, GM, Chvala, R, Brezin, J, et al. Long-Term Function and Survival of Elderly Donor Kidneys Transplanted into Young Adults. Transplantation (1998) 65(2):282–5. doi:10.1097/00007890-199801270-00027
57. Lionaki, S, Kapsia, H, Makropoulos, I, Metsini, A, Skalioti, C, Zavos, G, et al. Kidney Transplantation Outcomes from Expanded Criteria Donors, Standard Criteria Donors or Living Donors Older Than 60 Years. Ren Fail (2014) 36(4):526–33. doi:10.3109/0886022X.2013.876348
58. Locke, JE, Segev, DL, Warren, DS, Simpkins, CE, Montgomery, RA, and Dominici, F. Outcomes of Kidneys from Donors after Cardiac Death: Implications for Allocation and Preservation. Am J Transplant (2007) 7(7):1797–807. doi:10.1111/j.1600-6143.2007.01852.x
59. Mohan, S, Tanriover, B, Ali, N, Crew, RJ, Dube, GK, Radhakrishnan, J, et al. Availability, Utilization and Outcomes of Deceased Diabetic Donor Kidneys; Analysis Based on the UNOS Registry. Am J Transplant (2012) 12(8):2098–105. doi:10.1111/j.1600-6143.2012.04167.x
60. Moore, PS, Farney, AC, Rohr, MS, Gautreaux, MD, Rogers, J, Anderson, TK, et al. Dual Kidney Transplantation: A Case-Control Comparison with Single Kidney Transplantation from Standard and Expanded Criteria Donors. Transplantation (2007) 83(12):1551–6. doi:10.1097/01.tp.0000266579.11595.95
61. Papachristou, E, Provatopoulou, S, Savvidaki, E, Kaplanis, N, Kalliakmani, P, Papasotiriou, M, et al. Outcome of Transplantation in Renal Allograft Recipients from Cadaveric Donors with Standard and Expanded Criteria: A Single-Center Experience. Transplant Proc (2014) 46(9):3172–4. doi:10.1016/j.transproceed.2014.10.030
62. Saidi, RF, Elias, N, Kawai, T, Hertl, M, Farrell, ML, Delmonico, FL, et al. Outcome of Kidney Transplantation Using Expanded Criteria Donors and Donation after Cardiac Death Kidneys: Realities and Costs. Am J Transplant (2007) 7(12):2769–74. doi:10.1111/j.1600-6143.2007.01993.x
63. Serur, D, Kapur, S, Saal, S, Leeser, D, Gerber, LM, Wang, J, et al. Excellent Outcomes with Expanded Criteria Donor Kidneys: The Role of the Recipient’s Age. Clin transplants (2013) 85–91.
64. Smail, N, Baran, D, Mucsi, I, Cantarovich, M, Tchervenkov, J, Paraskevas, S, et al. Impact of Early Graft Function on 10-Year Graft Survival in Recipients of Kidneys from Standard- or Expanded-Criteria Donors. Transplantation (2013) 96(2):176–81. doi:10.1097/TP.0b013e318297443b
65. Song, SH, Lim, SH, Lee, J, Lee, JG, Huh, KH, Kim, SI, et al. Impact of Korea Network for Organ Sharing Expanded Donor Criteria on Delayed Graft Fuction in Kidney Transplantation: A Single-Center Experience. Transplant Proc (2018) 50(8):2363–7. doi:10.1016/j.transproceed.2018.04.046
66. Stratta, RJ, Farney, AC, Orlando, G, Farooq, U, Al-Shraideh, Y, Gautreaux, MD, et al. Dual Kidney Transplants from Adult Marginal Donors Successfully Expand the Limited Deceased Donor Organ Pool. Clin Transplant (2016) 30(4):380–92. doi:10.1111/ctr.12697
67. Sundberg, AK, Armstrong, G, Hairston, G, Hartmann, E, Farney, AC, Roskopf, J, et al. Increased Kidney Transplantation Utilizing Expanded Criteria Deceased Organ Donors with Results Comparable to Standard Criteria Donor Transplant. Ann Surg (2004) 239(5):688–97. doi:10.1097/01.sla.0000124296.46712.67
68. Swami, YK, Singh, DV, Gupta, SK, Pradhan, AA, Rana, YPS, Harkar, S, et al. Deceased Donor Renal Transplantation at Army Hospital Research and Referral: Our Experience. Indian J Urol (2013) 29(2):105–9. doi:10.4103/0970-1591.114029
69. Tomita, Y, Iwadoh, K, Nakajima, I, Fuchinoue, S, and Tojimbara, T. Long-Term Outcomes in Kidney Transplantation from Expanded-Criteria Donors after Circulatory Death. Transplant Proc (2017) 49(1):45–8. doi:10.1016/j.transproceed.2016.10.009
70. Yap, YT, Ho, QY, Kee, T, Ng, CY, and Chionh, CY. Impact of Pre-Transplant Biopsy on 5-Year Outcomes of Expanded Criteria Donor Kidney Transplantation. Nephrology (Carlton, Vic) (2021) 26(1):70–7. doi:10.1111/nep.13788
71. Antonieta Azancot, M, Moreso, F, Cantarell, C, Perello, M, Torres, IB, Sellares, J, et al. The Reproducibility and Predictive Value on Outcome of Renal Biopsies from Expanded Criteria Donors. Kidney Int (2014) 85(5):1161–8. doi:10.1038/ki.2013.461
72. Nardo, B, Bertelli, R, Cavallari, G, Capocasale, E, Cappelli, G, Mazzoni, MP, et al. Analysis of 80 Dual-Kidney Transplantations: A Multicenter Experience. Transplant Proc (2011) 43(5):1559–65. doi:10.1016/j.transproceed.2010.11.030
73. Dedinska, I, Palkoci, B, Vojtko, M, Osinova, D, and Lajiakova, M. Experiences with Expanded Criteria Donors: 10-Year Analysis of the Martin, Slovakia Transplant Center. Exp Clin Transplant (2019) 17(1):6–10. doi:10.6002/ect.2017.0188
74. Gambino, G, Gioviale, MC, Maione, C, Di Bona, A, Buffa, D, Virzi, C, et al. Use of Marginal Donors in Kidney Transplantation: Our Experience. Transplant Proc (2006) 38(4):999–1000. doi:10.1016/j.transproceed.2006.02.148
75. Hamed, MO, Watson, CJ, Bradley, JA, Pettigrew, G, Saeb-Parsy, K, Chen, Y, et al. Early Graft Loss after Kidney Transplantation: Risk Factors and Consequences. Am J Transplant (2015) 15(6):1632–43.
76. Mezrich, JD, Pirsch, JD, Fernandez, LA, Foley, DP, Bellingham, JM, Odorico, JS, et al. Differential Outcomes of Expanded-Criteria Donor Renal Allografts According to Recipient Age. Clin J Am Soc Nephrol (2012) 7(7):1163–71. doi:10.2215/CJN.00150112
77. Palkoci, B, Vojtko, M, Fialova, J, Osinova, D, and Lajciakova, M. Results of Kidney Transplantation from Expanded Criteria Donors: A Single-Center Experience. Int J Organ Transplant Med (2018) 9(1):1–9.
78. Saudan, P, Berney, T, Goumaz, C, Morel, P, and Martin, PY. Renal Transplantation with Donors Aged Over 50: A Long-Term, Single Centre Experience. Swiss Med weekly (2001) 131(9–10):117–21. doi:10.4414/smw.2001.06145
79. Olaverri, JG, Christian, JM, Elorrieta, P, Esnaola, K, Rodriguez, P, Marron, I, et al. Utilization of Advanced-Age Donors in Renal Transplantation. Transplant Proc (2011) 43(9):3340–3. doi:10.1016/j.transproceed.2011.09.089
80. Basar, H, Scantlebury, VP, McCauley, J, Irish, W, Fung, JJ, Soran, A, et al. Renal Transplantation in Recipients over the Age of 60: The Impact of Donor Age. Transplantation (1999) 67(8):1191–3. doi:10.1097/00007890-199904270-00019
81. Carmellini, M, Vistoli, F, Boggi, U, Bellini, R, and Mosca, F. Delayed Graft Function Incidence as Predictive Variable of Survival of Kidney Grafts Retrieved from Elderly Donors. Transplant Proc (2000) 32(1):128–30. doi:10.1016/s0041-1345(99)00909-4
82. Collins, MG, Chang, SH, Russ, GR, and McDonald, SP. Outcomes of Transplantation Using Kidneys from Donors Meeting Expanded Criteria in Australia and New Zealand, 1991 to 2005. Transplantation (2009) 87(8):1201–9. doi:10.1097/TP.0b013e31819ec3a6
83. Di Cocco, P, Orlando, G, D’Angelo, M, Rizza, V, De Luca, L, Famulari, A, et al. Kidney Transplantation from Older Donors. Transplant Proc (2011) 43(4):1033–5. doi:10.1016/j.transproceed.2011.01.149
84. Favi, E, Puliatti, C, Iesari, S, Monaco, A, Ferraresso, M, and Cacciola, R. Impact of Donor Age on Clinical Outcomes of Primary Single Kidney Transplantation from Maastricht Category-III Donors after Circulatory Death. Transplant direct (2018) 4(10):e396. doi:10.1097/TXD.0000000000000835
85. Galeano, C, Marcen, R, Jimenez, S, Fernandez Rodriguez, A, Sosa, H, Villafruela, JJ, et al. Utilization of Elderly Kidney Donors (>70 Years) Does Not Affect Graft Survival in the Medium Term. Transplant Proc (2010) 42(10):3935–7. doi:10.1016/j.transproceed.2010.08.069
86. Han, SY, Kong, JM, Kwon, OJ, Kim, MG, Jung, CW, Kim, SH, et al. Outcomes of Kidney Transplantation from Elderly Deceased Donors of a Korean Registry. PloS one (2020) 15(6 June):e0232177. doi:10.1371/journal.pone.0232177
87. Peters-Sengers, H, Arashi, D, Van Der Heide, JJH, Ten Berge, IJM, Bemelman, FJ, Idu, MM, et al. Stretching the Limits of Renal Transplantation in Elderly Recipients of Grafts from Elderly Deceased Donors. J Am Soc Nephrol (2017) 28(2):621–31.
88. Rao, KV, Kasiske, BL, Odlund, MD, Ney, AL, and Andersen, RC. Influence of Cadaver Donor Age on Posttransplant Renal Function and Graft Outcome. Transplantation (1990) 49(1):91–5. doi:10.1097/00007890-199001000-00020
89. Sekta, S, Ziaja, J, Klimunt, J, Krol, R, Cierpka, L, Kolonko, A, et al. Donation and Transplantation of Kidneys Harvested from Deceased Donors over the Age of 60 Years in the Upper Silesia Region. Transplant Proc (2016) 48(5):1466–71. doi:10.1016/j.transproceed.2015.11.038
90. Snoeijs, MGJ, Schaefer, S, Buurman, WA, Van Heurn, LWE, Christiaans, MH, Van Hooff, JP, et al. Kidney Transplantation Using Elderly Non-Heart-Beating Donors: A Single-Center Experience. Am J Transplant (2006) 6(5 I):1066–71. doi:10.1111/j.1600-6143.2006.01312.x
91. Tekin, S, Yavuz, HA, Yuksel, Y, Demirbas, A, Yucetin, L, Ates, I, et al. Kidney Transplantation from Elderly Donor. Transplant Proc (2015) 47(5):1309–11. doi:10.1016/j.transproceed.2015.04.015
92. Gohh, R, Yango, A, Gautam, A, Monaco, AP, Morrissey, PE, and Colacchio, TA. Renal Transplant Survival from Older Donors: A Single Center Experience. Arch Surg (2004) 139(4):384–9. doi:10.1001/archsurg.139.4.384
93. Bilgin, N, Karakayali, H, Moray, G, Demirag, A, Arslan, G, Akkoc, H, et al. Outcome of Renal Transplantation from Elderly Donors. Transplant Proc (1998) 30(3):744–6. doi:10.1016/s0041-1345(98)00031-1
94. Gerbase-DeLima, M, de Marco, R, Mine, KL, Monteiro, F, Tedesco-Silva, H, and Medina-Pestana, JO. Impact of Combinations of Donor and Recipient Ages and Other Factors on Kidney Graft Outcomes. Front Immunol (2020) 11:954. doi:10.3389/fimmu.2020.00954
95. Hermanowicz, M, Przygoda, J, Podobinska, I, Lewandowska, D, Czerwinski, J, and Danielewicz, R. Organ Donation from Elderly Deceased Donors and Transplantation to Elderly Recipients in Poland: Numbers and Outcomes. Transplant Proc (2016) 48(5):1390–3. doi:10.1016/j.transproceed.2016.01.048
96. Messa, P, Brezzi, B, Cresseri, D, Berardinelli, L, Poli, F, Scalamogna, M, et al. Immediate Graft Function Positively Affects Long-Term Outcome of Renal Allografts from Older but Not from Younger Donors. Transplant Proc (2006) 38(10):3377–81. doi:10.1016/j.transproceed.2006.10.073
97. Messina, M, Diena, D, Dellepiane, S, Guzzo, G, Lo Sardo, L, Fop, F, et al. Long-Term Outcomes and Discard Rate of Kidneys by Decade of Extended Criteria Donor Age. Clin J Am Soc Nephrol : CJASN (2017) 12(2):323–31. doi:10.2215/CJN.06550616
98. Navarro, MD, Lopez-Andreu, M, Rodriguez-Benot, A, Morales, MLA, Garcia, PA, Ortega-Salas, R, et al. Significance of Preimplantation Analysis of Kidney Biopsies from Expanded Criteria Donors in Long-Term Outcome. Transplantation (2011) 91(4):432–9. doi:10.1097/TP.0b013e318204bdd7
99. Akoh, JA, and Rana, TA. Impact of Donor Age on Outcome of Kidney Transplantation from Controlled Donation after Cardiac Death. Saudi J kidney Dis Transplant (2013) 24(4):673–81. doi:10.4103/1319-2442.113846
100. Cohen, EP, Hariharan, S, McBride, MA, and Bennett, LE. Risk Factors for Renal Allograft Survival from Older Cadaver Donors. Transplantation (1997) 64(12):1748–54. doi:10.1097/00007890-199712270-00022
101. Donnelly, PK, Simpson, AR, Milner, AD, Nicholson, ML, Horsburgh, T, Veitch, PS, et al. Age-Matching Improves the Results of Renal Transplantation with Older Donors. Nephrol Dial Transplant (1990) 5(9):808–11. doi:10.1093/ndt/5.9.808
102. Foster, MC, Wenham, PW, Rowe, PA, Blamey, RW, Bishop, MC, Burden, RP, et al. Use of Older Patients as Cadaveric Kidney Donors. Br J Surg (1988) 75(8):767–9. doi:10.1002/bjs.1800750815
103. Kwon, OJ, Lee, HG, and Kwak, JY. The Impact of Donor and Recipient Age on the Outcome of Kidney Transplantation. Transplant Proc (2004) 36(7):2043–5. doi:10.1016/j.transproceed.2004.07.047
104. Lloveras, J, Arcos, E, Comas, J, Crespo, M, and Pascual, J. A Paired Survival Analysis Comparing Hemodialysis and Kidney Transplantation from Deceased Elderly Donors Older Than 65 Years. Transplantation (2015) 99(5):991–6. doi:10.1097/TP.0000000000000474
105. Mizutani, K, Yamada, S, Katoh, N, Ono, Y, Ohshima, S, Kinukawa, T, et al. Cadaveric Kidneys from Older Donors and Their Effective Use in Transplantation: A Risk Factor for Long-Term Graft Survival. Transplant Proc (1997) 29(1–2):113–5. doi:10.1016/s0041-1345(96)00028-0
106. Morling, N, Ladefoged, J, Lange, P, Nerstrom, B, Nielsen, B, Nielsen, LS, et al. Kidney Transplantation and Donor Age. Tissue Antigens (1975) 6(3):163–6. doi:10.1111/j.1399-0039.1975.tb00630.x
107. Nakatani, T, Kim, T, Uchida, J, Kumada, N, Tsuchida, K, Takemoto, Y, et al. Clinical Study on 53 Cases of Cadaveric Kidney Transplantation at Osaka City University Hospital. Osaka city Med J (2001) 47(2):95–103.
108. Pessione, F, Cohen, S, Durand, D, Hourmant, M, Kessler, M, Legendre, C, et al. Multivariate Analysis of Donor Risk Factors for Graft Survival in Kidney Transplantation. Transplantation (2003) 75(3):361–7. doi:10.1097/01.TP.0000044171.97375.61
109. Pirsch, JD, D’Alessandro, AM, Sollinger, HW, Hoffmann, RM, Roecker, E, Voss, BJ, et al. The Effect of Donor Age, Recipient Age, and HLA Match on Immunologic Graft Survival in Cadaver Renal Transplant Recipients. Transplantation (1992) 53(1):55–9. doi:10.1097/00007890-199201000-00010
110. Shaheen, MF, Al Sayyari, A, Shaheen, FAM, Attar, B, Elamin, K, and Al Hayyan, H. Impact of Recipient and Donor Nonimmunologic Factors on the Outcome of Deceased Donor Kidney Transplantation. Transplant Proc (2010) 42(1):273–6. doi:10.1016/j.transproceed.2009.12.052
111. Snoeijs, MGJ, Buurman, WA, Christiaans, MHL, van Hooff, JP, Goldschmeding, R, van Suylen, RJ, et al. Histological Assessment of Preimplantation Biopsies May Improve Selection of Kidneys from Old Donors after Cardiac Death. Am J Transplant (2008) 8(9):1844–51. doi:10.1111/j.1600-6143.2008.02318.x
112. Vivas, CA, O’Donovan, RM, Jordan, ML, Hickey, DP, Hrebinko, R, Shapiro, R, et al. Cadaveric Renal Transplantation Using Kidneys from Donors Greater Than 60 Years Old. Clin Transplant (1992) 6(2):77–80. doi:10.1111/j.1399-0012.1992.tb00595.x
113. Wahlberg, J, Tufveson, G, Larsson, A, Backman, U, and Frodin, L. Influence of the Age of Cadaveric Kidney Donors on Transplantation Outcome and Rate of Surgical Complications. Scand J Urol Nephrol Supplementum (1990) 131:39–42.
114. Ballesteros, MA, Suberviola, B, Belmar Vega, L, Ruiz San Millan, JC, Fernandez-Santiago, R, Campos Fernandez, S, et al. Impact of the Elderly Donor on an Abdominal Organ Transplantation Program. Eur Surg - Acta Chirurgica Austriaca (2020) 52(5):223–8. doi:10.1007/s10353-020-00637-0
115. Burrows, L, and Knight, RJ. The Combined Impact of Donor Age and Acute Rejection on Long-Term Cadaver Renal Allograft Survival. Surgery (1999) 125(3):0318–24. doi:10.1067/msy.1999.95681
116. Buxeda, A, Velis, G, Arias-Cabrales, C, Zapatero, A, Burballa, C, Redondo-Pachon, D, et al. Kidney Transplantation Outcomes from Elderly Donors after Circulatory Death: A Comparison with Elderly Brain-Dead Donors. Clin kidney J (2021) 14(4):1181–9. doi:10.1093/ckj/sfaa114
117. Lim, WH, Chang, S, Chadban, S, Campbell, S, Dent, H, Russ, GR, et al. Donor-Recipient Age Matching Improves Years of Graft Function in Deceased-Donor Kidney Transplantation. Nephrol Dial Transplant (2010) 25(9):3082–9. doi:10.1093/ndt/gfq127
118. Magott-Procelewska, M, Madziarska, K, Boratynska, M, Chudoba, P, Lepiesza, A, Mazanowska, O, et al. Kidney Transplantation from Old Deceased Donors: Impact of Uric Acid Level-A Quarter-Century of Experience in One Transplant Center. Transplant Proc (2018) 50(6):1701–4. doi:10.1016/j.transproceed.2018.02.127
119. Martins, J, Barreto, S, Bravo, P, Santos, JP, Ferreira, MJ, Oliveira, C, et al. Kidney Transplant from Elderly Donors: A Center Experience. Transplant Proc (2020) 52(5):1265–8. doi:10.1016/j.transproceed.2019.12.051
120. Oppenheimer, F, Aljama, P, Asensio Peinado, C, Bustamante Bustamante, J, Crespo Albiach, JF, and Guirado Perich, L. The Impact of Donor Age on the Results of Renal Transplantation. Nephrol Dial Transplant (2004) 19:iii11–5. doi:10.1093/ndt/gfh1008
121. Perez-Saez, MJ, Lafuente Covarrubias, O, Hernandez, D, Moreso, F, Melilli, E, Juega, J, et al. Early Outcomes of Kidney Transplantation from Elderly Donors after Circulatory Death (GEODAS Study). BMC Nephrol (2019) 20(1):233. doi:10.1186/s12882-019-1412-0
122. Resende, L, Guerra, J, Santana, A, Mil-Homens, C, Abreu, F, and da Costa, AG. Impact of Donor Age on Renal Allograft Function and Survival. Transplant Proc (2009) 41(3):794–6. doi:10.1016/j.transproceed.2009.01.064
123. Roselli, E, Rossetti, O, Soldano, S, Aseni, P, Colombo, V, De Gasperi, A, et al. Renal Grafts from Elderly Donors: Histological Studies and Long-Term Results. Transplant Proc (2007) 39(6):1820–2. doi:10.1016/j.transproceed.2007.05.034
124. Thornton, SR, Hamilton, N, Evans, D, Fleming, T, Clarke, E, Morgan, J, et al. Outcome of Kidney Transplantation from Elderly Donors after Cardiac Death. Transplant Proc (2011) 43(10):3686–9. doi:10.1016/j.transproceed.2011.09.078
125. Hricik, DE, Poggio, ED, Woodside, KJ, Sarabu, N, Sanchez, EQ, Schulak, JA, et al. Effects of Cellular Sensitization and Donor Age on Acute Rejection and Graft Function after Deceased-Donor Kidney Transplantation. Transplantation (2013) 95(10):1254–8. doi:10.1097/TP.0b013e31828ad866
126. Park, WY, Choi, MS, Kim, YS, Choi, BS, Park, CW, Yang, CW, et al. Impact of Acute Kidney Injury in Expanded Criteria Deceased Donors on Post-Transplant Clinical Outcomes: Multicenter Cohort Study. BMC Nephrol (2019) 20(1):39. doi:10.1186/s12882-019-1225-1
127. Yu, CC, Ho, HC, Ou, YC, Cheng, CL, Su, CK, Chen, WM, et al. Kidneys from Standard-Criteria Donors with Different Severities of Terminal Acute Kidney Injury. Transplant Proc (2014) 46(10):3335–8. doi:10.1016/j.transproceed.2014.11.002
128. Hall, IE, Schroppel, B, Doshi, MD, Ficek, J, Weng, FL, Hasz, RD, et al. Associations of Deceased Donor Kidney Injury with Kidney Discard and Function after Transplantation. Am J Transplant (2015) 15(6):1623–31. doi:10.1111/ajt.13144
129. Boffa, C, van de Leemkolk, F, Curnow, E, Homan van der Heide, J, Gilbert, J, Sharples, E, et al. Transplantation of Kidneys from Donors with Acute Kidney Injury: Friend or Foe? Am J Transpl (2017) 17(2):411–9. doi:10.1111/ajt.13966
130. Yu, Myeon, Kim, YC, Yu, BC, Min, SI, Ha, J, Yang, J, et al. Trend, Not Severity, of Acute Kidney Injury Affects Graft Outcome in Deceased Donor Kidney Transplantation. Clin Transplant (2018) 32(12):e13431. doi:10.1111/ctr.13431
131. Torabi, J, Graham, JA, Choinski, K, Suresh, S, Chokechanachaisakul, A, Ajaimy, M, et al. Young Donors with Severe Acute Kidney Injury Offer an Opportunity to Expand the Donor Pool. Am J Surg (2019) 218(1):7–13. doi:10.1016/j.amjsurg.2019.04.005
132. Kwon, JA, Park, H, Park, SJ, Cho, HR, Noh, M, Kwon, EK, et al. Factors of Acute Kidney Injury Donors Affecting Outcomes of Kidney Transplantation from Deceased Donors. Transplant Proc (2019) 51(8):2575–81. doi:10.1016/j.transproceed.2019.03.068
133. van der Windt, DJ, Jorgensen, DR, Bou-Samra, P, Molinari, M, Wijkstrom, M, Ganoza, A, et al. Donor Acute Kidney Injury and its Effect on 1-Year Post-Transplant Kidney Allograft Fibrosis. Clin Transplant (2020) 34(2):e13770. doi:10.1111/ctr.13770
134. Park, WY, Chang, YK, Kim, YS, Jin, K, Yang, CW, Han, S, et al. Impact of Acute Kidney Injury in Deceased Donors with High Kidney Donor Profile Index on Posttransplant Clinical Outcomes: A Multicenter Cohort Study. Kidney Res Clin Pract (2021) 40(1):162–74. doi:10.23876/j.krcp.20.083
135. Jung, CW, Park, KT, Kim, SY, Kim, SJ, Kim, MG, Jo, SK, et al. Clinical Outcomes in Kidney Transplantation Patients from Deceased Donors with Acute Kidney Injury. Transplant Proc (2013) 45(8):2941–5. doi:10.1016/j.transproceed.2013.08.048
136. Farney, AC, Rogers, J, Orlando, G, Al-Geizawi, S, Buckley, M, Farooq, U, et al. Evolving Experience Using Kidneys from Deceased Donors with Terminal Acute Kidney Injury. J Am Coll Surgeons (2013) 216(4):645–55. doi:10.1016/j.jamcollsurg.2012.12.020
137. Ko, KJ, Kim, YH, Kim, MH, Jun, KW, Kwon, KH, Kim, HS, et al. Kidney Transplantation Using Expanded Criteria Deceased Donors with Terminal Acute Kidney Injury: A Single Center Experience in Korea. Ann Surg Treat Res (2018) 95(5):278–85. doi:10.4174/astr.2018.95.5.278
138. Ugarte, R, Kraus, E, Montgomery, RA, Burdick, JF, Ratner, L, Haas, M, et al. Excellent Outcomes after Transplantation of Deceased Donor Kidneys with High Terminal Creatinine and Mild Pathologic Lesions. Transplantation (2005) 80(6):794–800. doi:10.1097/01.tp.0000173801.33878.bf
139. Karachristos, A, Herrera, A, Darrah, J, Baribault, C, Lee, I, Leech, SH, et al. Outcomes of Renal Transplantation in Older High Risk Recipients: Is There an Age Effect? J Surg Res (2010) 161(2):173–8.
140. Sohrabi, S, Navarro, AP, Wilson, C, Sanni, A, Wyrley-Birch, H, Anand, DV, et al. Donation after Cardiac Death Kidneys with Low Severity Pre-Arrest Acute Renal Failure. Am J Transplant (2007) 7(3):571–5. doi:10.1111/j.1600-6143.2006.01639.x
141. Zuckerman, JM, Singh, RP, Farney, AC, Rogers, J, and Stratta, RJ. Single Center Experience Transplanting Kidneys from Deceased Donors with Terminal Acute Renal Failure. Surgery (2009) 146(4):686–94. doi:10.1016/j.surg.2009.06.036
142. Rodrigo, E, Pinera, C, Fernandez-Fresnedo, G, Ruiz, J, Ruiz, J, Gago, M, et al. Using RIFLE Criteria to Evaluate Acute Kidney Injury in Brain-Deceased Kidney Donors. Nephrol Dial Transplant (2010) 25(5):1531–7.
143. Kolonko, A, Wiecek, A, Chudek, J, Pawlik, A, Wilk, J, and Jalowiecki, P. Acute Kidney Injury before Organ Procurement Is Associated with Worse Long-Term Kidney Graft Outcome. Transplant Proc (2011) 43(8):2871–4. doi:10.1016/j.transproceed.2011.07.017
144. Yuan, XP, Han, M, Wang, XP, Zhou, J, Jiao, XY, Wang, CX, et al. Kidney Transplantation from Cardiac Death Donors with Terminal Acute Renal Failure. Transpl Proc (2014) 46(4):1057–60. doi:10.1016/j.transproceed.2013.11.055
145. Lee, MH, Jeong, EG, Chang, JY, Kim, Y, Kim, JI, Moon, IS, et al. Clinical Outcome of Kidney Transplantation from Deceased Donors with Acute Kidney Injury by Acute Kidney Injury Network Criteria. J Crit Care (2014) 29(3):432–7. doi:10.1016/j.jcrc.2013.12.016
146. Molina, M, Apaza, J, Gonzalez Monte, E, Gutierrez Martinez, E, Sevillano, AM, Polanco, N, et al. Results of Kidney Transplantation from Deceased Donors with Acute Kidney Injury. Transplant Proc (2015) 47(1):42–4. doi:10.1016/j.transproceed.2014.11.007
147. Ali, T, Dimassi, W, Elgamal, H, Alabassi, A, Aleid, H, Altalhi, M, et al. Outcomes of Kidneys Utilized from Deceased Donors with Severe Acute Kidney Injury. QJM (2015) 108(10):803–11. doi:10.1093/qjmed/hcv033
148. Gwon, JG, Jung, CW, Kim, MG, Park, KT, and Ko, SY. Clinical Outcomes in Kidney Transplantation from Deceased Donors with Acute Kidney Injury Based on Acute Kidney Injury Network Criteria. Transplant Proc (2018) 50(8):2426–30. doi:10.1016/j.transproceed.2018.03.072
149. Bauer, J, Grzella, S, Bialobrzecka, M, Berger, L, Viebahn, R, Schenker, P, et al. Success of Kidney Transplantations from Deceased Donors with Acute Kidney Injury. Ann Transplant (2018) 23:836–44. doi:10.12659/AOT.912660
150. Jiang, Y, Song, T, Liu, J, Wang, Z, Wang, X, Huang, Z, et al. Single Kidney Transplantation from Donors with Acute Kidney Injury: A Single-Center Experience. Pediatr Transplant (2019) 23(3):e13326. doi:10.1111/petr.13326
151. Cima, L, Ghimenton, C, Valotto, G, Brunelli, M, Eccher, A, Nacchia, F, et al. Histopathology and Long-Term Outcome of Kidneys Transplanted from Donors with Severe Acute Kidney Injury. Prog Transplant (Aliso Viejo, Calif) (2019) 29(1):36–42. doi:10.1177/1526924818817054
152. Domagala, P, Gorski, L, Wszola, M, Kieszek, R, Diuwe, P, Goralski, P, et al. Successful Transplantation of Kidneys from Deceased Donors with Terminal Acute Kidney Injury. Ren Fail (2019) 41(1):167–74. doi:10.1080/0886022X.2019.1590209
153. Schutte-Nutgen, K, Finke, M, Ehlert, S, Tholking, G, Pavenstadt, H, Suwelack, B, et al. Expanding the Donor Pool in Kidney Transplantation: Should Organs with Acute Kidney Injury Be Accepted? A Retrospective Study. PloS one (2019) 14(3):e0213608. doi:10.1371/journal.pone.0213608
154. Liu, C, Hall, IE, Mansour, S, Thiessen Philbrook, HR, Jia, Y, and Parikh, CR. Association of Deceased Donor Acute Kidney Injury with Recipient Graft Survival. JAMA Netw open (2020) 3(1):e1918634. doi:10.1001/jamanetworkopen.2019.18634
155. Ko, K, Kim, YH, Kim, MH, Jun, KW, Hwang, JK, Kim, SD, et al. Effect of Donor-Recipient Age Match in Expanded Criteria Deceased Donor Kidney Transplantation. Transplant Proc (2017) 49(5):982–6. doi:10.1016/j.transproceed.2017.03.058
156. Pérez-Sáez, MJ, Juega, J, Zapatero, A, Comas, J, Tort, J, Lauzurica, R, et al. Kidney Transplant Outcomes in Elderly Recipients with Controlled Donation after Circulatory Death or Donation after Brain Death Donors: A Registry Cohort Study. Transpl Int (2021) 34(12):2507–14.
157. Sánchez-Fructuoso, AI, Pérez-Flores, I, Del Río, F, Blázquez, J, Calvo, N, et al. Moreno de la Higuera MÁ Uncontrolled Donation after Circulatory Death: A Cohort Study of Data from a Long-Standing Deceased-Donor Kidney Transplantation Program. Am J Transpl (2019) 19(6):1693–707. doi:10.1111/ajt.15243
158. Molina, M, Guerrero-Ramos, F, Fernández-Ruiz, M, González, E, Cabrera, J, Morales, E, et al. Kidney Transplant from Uncontrolled Donation after Circulatory Death Donors Maintained by nECMO Has Long-Term Outcomes Comparable to Standard Criteria Donation after Brain Death. Am J Transpl (2019) 19(2):434–47. doi:10.1111/ajt.14991
159. Aida, N, Ito, T, Kurihara, K, Naka Mieno, M, Nakagawa, Y, and Kenmochi, T. Analysis of Risk Factors for Donation after Circulatory Death Kidney Transplantation in Japan. Clin Exp Nephrol (2022) 26(1):86–94. doi:10.1007/s10157-021-02128-2
160. Chen, G, Wang, C, Ko, DSC, Qiu, J, Yuan, X, Han, M, et al. Comparison of Outcomes of Kidney Transplantation from Donation after Brain Death, Donation after Circulatory Death, and Donation after Brain Death Followed by Circulatory Death Donors. Clin Transpl (2017) 31(11). doi:10.1111/ctr.13110
161. Snoeijs, MGJ, Winkens, B, Heemskerk, MBA, Hoitsma, AJ, Christiaans, MHL, Buurman, WA, et al. Kidney Transplantation from Donors after Cardiac Death: A 25-Year Experience. Transplantation (2010) 90(10):1106–12. doi:10.1097/TP.0b013e3181f83b0b
162. Trotter, PB, Jochmans, I, Hulme, W, Robb, M, Watson, C, Neuberger, J, et al. Transplantation of Kidneys from DCD and DBD Donors Who Died after Ligature Asphyxiation: The UK Experience. Am J Transpl (2018) 18(11):2739–51. doi:10.1111/ajt.14989
163. Yuan, Xpeng, Han, M, Wang, Xping, Zhou, J, Chen, Cbao, and shun, HX. One Center’s Experiences of 101 Cases of Kidney Transplants from Cardiac Death Donors. Exp Clin Transpl (2014) 12(4):304–9.
164. Savoye, E, Legeai, C, Branchereau, J, Gay, S, Riou, B, Gaudez, F, et al. Optimal Donation of Kidney Transplants after Controlled Circulatory Death. Am J Transpl (2021) 21(7):2424–36. doi:10.1111/ajt.16425
165. Heylen, L, Jochmans, I, Samuel, U, Tieken, I, Naesens, M, Pirenne, J, et al. The Duration of Asystolic Ischemia Determines the Risk of Graft Failure after Circulatory-Dead Donor Kidney Transplantation: A Eurotransplant Cohort Study. Am J Transpl (2018) 18(4):881–9. doi:10.1111/ajt.14526
166. Kostakis, ID, Kassimatis, T, Flach, C, Karydis, N, Kessaris, N, and Loukopoulos, I. Hypoperfusion Warm Ischaemia Time in Renal Transplants from Donors after Circulatory Death. Nephrol Dial Transpl (2020) 35(9):1628–34. doi:10.1093/ndt/gfaa160
167. Lafuente, O, Sánchez-Sobrino, B, Pérez, M, López-Sánchez, P, Janeiro, D, Rubio, E, et al. Midterm Results of Renal Transplantation from Controlled Cardiac Death Donors Are Similar to Those from Brain Death Donors. Transpl Proc (2016) 48(9):2862–6. doi:10.1016/j.transproceed.2016.08.039
168. Lia, D, Singer, P, Nair, V, Yang, J, Teperman, L, and Grodstein, E. DCD Renal Transplantation from Donors with Acute Kidney Injury. Transplantation (2021) 105(4):886–90. doi:10.1097/TP.0000000000003317
169. Miñambres, E, Rodrigo, E, Suberviola, B, Valero, R, Quintana, A, Campos, F, et al. Strict Selection Criteria in Uncontrolled Donation after Circulatory Death Provide Excellent Long-Term Kidney Graft Survival. Clin Transpl (2020) 34(9):e14010. doi:10.1111/ctr.14010
170. Chopra, B, Sureshkumar, KK, Rajasundaram, D, and Rodrigo, EC. Outcomes of Kidney Transplant Recipients (KTRs) Comparing Brain Dead Donors’ vs Donation after Cardiac Death Stratified by KDPI, Focus on Marginal Kidneys: A UNOS Database Analysis. Am J Transplant 21(S4):356–7.
171. Axelrod, DA, Schnitzler, MA, Xiao, H, Irish, W, Tuttle-Newhall, E, Chang, SH, et al. An Economic Assessment of Contemporary Kidney Transplant Practice. Am J Transplant (2018) 18(5):1168–76. doi:10.1111/ajt.14702
172. Whiting, JF, Woodward, RS, Zavala, EY, Cohen, DS, Martin, JE, Singer, GG, et al. Economic Cost of Expanded Criteria Donors in Cadaveric Renal Transplantation: Analysis of Medicare Payments. Transplantation (2000) 70(5):755–60. doi:10.1097/00007890-200009150-00007
173. Yaffe, HC, von Ahrens, D, Urioste, A, Mas, VR, and Akalin, E. Impact of Deceased-Donor Acute Kidney Injury on Kidney Transplantation. Transplantation (2024) 108(6):1283–95. doi:10.1097/TP.0000000000004848
174. Rosaasen, C, Rosaasen, N, Mainra, R, Trachtenberg, A, Ho, J, Parsons, C, et al. Waitlisted and Transplant Patient Perspectives on Expanding Access to Deceased-Donor Kidney Transplant: A Qualitative Study. Can J Kidney Health Dis (2022) 9:20543581221100291. doi:10.1177/20543581221100291
175. Tingle, SJ, Figueiredo, RS, Moir, JA, Goodfellow, M, Talbot, D, and Wilson, CH. Machine Perfusion Preservation versus Static Cold Storage for Deceased Donor Kidney Transplantation. Cochrane Database Syst Rev (2019) 2019(3):CD011671. doi:10.1002/14651858.CD011671.pub2
176. Tedesco Silva, H, Ramos, TRde M, de Carvalho, DDBM, Ferreira, GF, de Andrade, JMM, de Andrade, LGM, et al. Use of Machine Perfusion to Increase the Number of Expanded Criteria Deceased Donor Kidney Transplants: A Pharmacoeconomic Analysis. Transpl Direct (2024) 10(8):e1668. doi:10.1097/TXD.0000000000001668
177. Cho, YW, Bunnapradist, S, Cho, ES, Stadtler, M, Simmons, V, Locke, J, et al. Can Machine Perfusion Decrease the Likelihood of Discard Among Biopsied Kidneys? Transpl Proc (2008) 40(4):1029–31. doi:10.1016/j.transproceed.2008.03.062
178. Stewart, DE, Garcia, VC, Rosendale, JD, Klassen, DK, and Carrico, BJ. Diagnosing the Decades-Long Rise in the Deceased Donor Kidney Discard Rate in the United States. Transplantation (2017) 101(3):575–87. doi:10.1097/TP.0000000000001539
179. Lentine, KL, Kasiske, B, and Axelrod, DA. Procurement Biopsies in Kidney Transplantation: More Information May Not Lead to Better Decisions. J Am Soc Nephrol (2021) 32(8):1835–7. doi:10.1681/ASN.2021030403
180. Sung, RS, Christensen, LL, Leichtman, AB, Greenstein, SM, Distant, DA, Wynn, JJ, et al. Determinants of Discard of Expanded Criteria Donor Kidneys: Impact of Biopsy and Machine Perfusion. Am J Transplant (2008) 8(4):783–92. doi:10.1111/j.1600-6143.2008.02157.x
181. Keijbeck, A, Veenstra, R, Pol, RA, Konijn, C, Jansen, N, Van Goor, H, et al. The Association between Macroscopic Arteriosclerosis of the Renal Artery, Microscopic Arteriosclerosis, Organ Discard, and Kidney Transplant Outcome. Transplantation (2020) 104(12):2567–74. doi:10.1097/TP.0000000000003189
182. Yi, Z, Xi, C, Menon, MC, Cravedi, P, Tedla, F, Soto, A, et al. A Large-Scale Retrospective Study Enabled Deep-Learning Based Pathological Assessment of Frozen Procurement Kidney Biopsies to Predict Graft Loss and Guide Organ Utilization. Kidney Int (2024) 105(2):281–92. doi:10.1016/j.kint.2023.09.031
183. Pierobon, ES, Sandrini, S, De Fazio, N, Rossini, G, Fontana, I, Boschiero, L, et al. Optimizing Utilization of Kidneys from Deceased Donors over 60 Years: Five-Year Outcomes after Implementation of a Combined Clinical and Histological Allocation Algorithm. Transpl Int (2013) 26(8):833–41. doi:10.1111/tri.12135
Keywords: kidney transplant, decision making, utilization, organ discard, clinical practice guideline
Citation: Dionne JC, Campbell P, Cardinal H, Giannidis T, Goldberg A, Kim SJ, Knoll G, Pâquet M, Parsons C, Yuan Y and Mainra R (2025) Optimizing the Use of Deceased Donor Kidneys at Risk of Discard: A Clinical Practice Guideline. Transpl. Int. 38:14596. doi: 10.3389/ti.2025.14596
Received: 09 March 2025; Accepted: 11 June 2025;
Published: 26 June 2025.
Copyright © 2025 Dionne, Campbell, Cardinal, Giannidis, Goldberg, Kim, Knoll, Pâquet, Parsons, Yuan and Mainra. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Rahul Mainra, cmFodWwubWFpbnJhQHVzYXNrLmNh