Donation after Circulatory Death Renal Allografts—Does Donor Age Greater than 50 Years Affect Recipient Outcomes?

Author's Accepted Manuscript Donation after Circulatory Death (DCD) Renal Allografts: Does Donor Age > 50 Affect Recipient Outcomes? Melissa J. Huynh , Philippe D. Violette , Neal E. Rowe , Corinne Weernink , Kelly Maclean , Alp Sener , Patrick P. Luke

PII: DOI: Reference:

S0022-5347(15)03943-9 10.1016/j.juro.2015.04.110 JURO 12606

To appear in: The Journal of Urology Accepted Date: 21 April 2015 Please cite this article as: Huynh MJ, Violette PD, Rowe NE, Weernink C, Maclean K, Sener A, Luke PP, Donation after Circulatory Death (DCD) Renal Allografts: Does Donor Age > 50 Affect Recipient Outcomes?, The Journal of Urology® (2015), doi: 10.1016/j.juro.2015.04.110. DISCLAIMER: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our subscribers we are providing this early version of the article. The paper will be copy edited and typeset, and proof will be reviewed before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to The Journal pertain.

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Donation after Circulatory Death (DCD) Renal Allografts: Does Donor Age > 50 Affect Recipient Outcomes? Authors: Melissa J. Huynh, MD1, Philippe D. Violette, MD CM1, Neal E. Rowe, MD1, Corinne

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Western University, Department of Surgery, Division of Urology

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Keywords: Renal, transplant, organ donation, kidney, age

Abstract word count: 250 Article word count: 2468 Tables: 3

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Figures: 2 Color figures: 2

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Multi-Organ Transplant Program, London Health Sciences Centre

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Weernink, Kelly Maclean, BScPharm, ACPR, Alp Sener, MD, PhD2, Patrick P. Luke, MD2

Corresponding author: [email protected] 339 Windermere Road London, Ontario N6A 5A5 Tel: (519) 663-3180 Fax: (519) 663-3858

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FOOTNOTES Authorship:

Philippe D. Violette, MD CM Statistics and data analysis, participated in writing of the paper Neal E. Rowe, MD Participated in writing of the paper and research design

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Corinne Weernink Database maintenance

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Kelly Maclean Data acquisition and verification Alp Sener, MD, PhD Participated in research design

Patrick P. Luke, MD Participated in writing of the paper and research design

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Authors addresses:

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Melissa J. Huynh, MD Primary author in writing of the paper, participated in research design, performance of research

Melissa J. Huynh St. Joseph’s Health Care, London 268 Grosvenor Street, Room B4-657 London, Ontario, Canada, N6A 4V2

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Philippe D. Violette St. Joseph’s Health Care, London 268 Grosvenor Street, Room B4-657 London, Ontario, Canada, N6A 4V2

Neal E. Rowe, MD 5991 Spring Garden Road, Suite 620 Halifax, NS B3H 1Y6 Corinne Weernink London Health Sciences Centre 339 Windermere Road London, Ontario N6A 5A5 Kelly Maclean London Health Sciences Centre

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339 Windermere Road London, Ontario N6A 5A5

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Alp Sener London Health Sciences Centre 339 Windermere Road London, Ontario N6A 5A5

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Patrick P. Luke London Health Sciences Centre 339 Windermere Road London, Ontario N6A 5A5

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Disclosures:

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Funding: This work was supported in part by a grant from the Urology Care Foundation Research Scholars Program and the Frank and Marion Hinman Urology Research Fund

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ABSTRACT Purpose: Donation after circulatory death (DCD) renal allografts are associated with excellent outcomes. We performed a retrospective chart review to investigate the impact of donor age on post-operative and

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intermediate-term outcomes. Materials & Methods: We compared recipient outcomes of DCD allografts from donors >50 years of age to those <50 years. Between July 2006 and September 2013, our institution performed 118 single

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DCD renal transplants. Outcome variables (creatinine clearance (CrCl)), readmission rate, length of hospital stay (LOS), delayed graft function (DGF), graft loss and rejection) were compared between the

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two age categories using Student’s t-test and Pearson chi-square test. Independent prognosticators of CrCl at 12 months were assessed with multivariate linear regression modeling.

Results: Mean recipient age was 53.8±14.7 years and 45.8% of DCD donors were >50 years of age. Median follow-up was 21 months (range 1 to 87). Recipients of kidney transplants from DCD donors >50 years of age demonstrated lower CrCl at 1 month (50.3±25.3 mL/min vs. 72.7±31.7 mL/min, p<0.001), 3

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months (62.5±22.9 mL/min vs 87.9±36.4 ml/min, p<0.001), and 1 year (66.2±26.8 mL/min vs 87.8±38.7 mL/min, p=0.013). However, the two groups did not differ with regard to DGF, graft loss, hospital readmissions, or LOS. Multivariate linear regression demonstrated that donor age, recipient age, recipient

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sex, and cold ischemia time were independent predictors of CrCl at 12 months. Conclusion: Recipients of allografts from donors >50 years of age demonstrated inferior renal function at

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1 year, but both groups had similar graft survival and short-term outcomes. Longer follow-up is required to determine long-term allograft survival.

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INTRODUCTION Historically, the main organ source in North America has been from neurological determination of death (NDD) donors (1,2). Reliance on organ donation after brain death limits the availability of organs for

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transplant, creating a renewed interest in organ donation after cardiac death (DCD). Worldwide, DCD transplantation has increased dramatically over the last decade (3,4). Despite this increase, DCD renal

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allografts account for only 10% of deceased donor renal transplants in the United States as of 2009 (5).

Despite a higher delayed graft function (DGF) rate (6), there are several studies demonstrating that long-

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term allograft function in DCD transplants are similar to that seen in NDD (1,2,7,8). Conversely, it is unknown whether or not DCD kidney allografts from older donors are more susceptible to impaired graft function or graft loss (1,4,9). An increasing proportion of DCD allografts are procured from donors over the age of 50, however detailed analysis of the functional implications beyond allograft survival are

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limited in this group of patients.

In order to provide quality assurance to our patients, we performed a retrospective analysis of a Canadian cohort of DCD renal transplants to determine whether or not a difference in early and intermediate term

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outcome exists between DCD allografts from donors over the age of 50 versus those 50 years of age and

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younger. We also identify variables that are associated with or predictive of outcomes.

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METHODS

Patients

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The study was approved by our institutional research ethics review board. We performed a retrospective chart review of 126 controlled DCD donors and graft recipients between July 2006 and September 2013 (Figure 1). DCD donors were identified by Ontario’s Organ Procurement Organization (OPO), the

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Trillium Gift of Life Network (TGLN). Although organs were procured from several Canadian centers, all transplants were performed by three transplant surgeons with similar experience at a single tertiary

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center. For donors at our institution, data points were collected by reviewing electronic and paper hospital charts. For the remaining donors from other Canadian centers, de-identified patient demographics and information were obtained from the Trillium Gift of Life Network. Demographic information collected included donor and recipient age, sex, comorbidities, height and weight. Fourteen of the allografts were considered expanded criteria donor (ECD) kidneys by criteria of age >50 with two of the following:

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terminal creatinine > 1.5 mg/dL (>133 umol/L), history of hypertension or associated cerebral vascular accident. Eight patients who received dual kidneys were excluded, bringing our evaluable population to 118, including 6 patients who had received kidney-pancreas transplants. Although donor implantation

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biopsies were performed, donor histology was not used to exclude organs for transplantation. The use of machine perfusion for graft preservation, as well as cold and warm ischemic times were also recorded.

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Length of followup was determined based on the last clinic appointment recorded in the hospital chart.

Outcome variables

We considered 12 month CrCl as our primary outcome in an a priori fashion, as this time point has been shown to be a surrogate marker for long-term renal allograft function and survival (Hariharan 2002). Secondary outcomes reflected by early post-transplant data included CrCl at 7 days, 1 month, and 3 months, in addition to delayed graft function, length of hospital stay, hospital readmissions, and graft rejection. Renal function was evaluated using creatinine clearance (CrCl) calculated from the Cockcroft-

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Gault equation. CrCl was recorded at 7 days, 1 month, 3 months and 12 months. Delayed graft function (DGF) was defined as the need for dialysis within 1 week of transplantation. Grafts were considered to have failed if the recipient required permanent dialysis after transplantation or explant of the graft. Graft

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failures were death censored. The hospital length of stay (LOS) was calculated as the number of days from the date of transplant to the date of discharge. Hospital readmissions were included in the analysis if the medical issue or complication was related to the transplant. Rejection episodes were identified as

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cause’, and there were no protocol biopsies performed.

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cellular, antibody-mediated or both, based on renal allograft biopsy. All biopsies were performed ‘for

Statistical Analysis

Statistical analyses were performed using SPSS V20. (Armonk, NY: IBM Corporation). Univariate analysis were conducted using independent Student t-test for continuous variables and Pearson χ2 for categorical variables. Multivariate linear regression modeling was used to identify independent predictors

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of CrCl at 12 months post-operatively. Assumptions of linearity, independence of errors, homoscedasticity and normality were verified (data not shown). A two tailed p-value of 0.05 was

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RESULTS

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considered significant.

Perioperative characteristics of donor and recipient groups Our donor population was 68.6% male (n=81) with a mean age of 43.4±14.5 years. Of these,

45.8% (n=54) were above 50 (mean 56.2±3.1 years, range 51.4-61.8), and 54.2% (n=64) were 50 or younger (mean 32.6±11.2 years, range 12.8 to 49.8), which defined our comparison groups. Fourteen of the allografts from donors in the 51 years and greater age group were considered ECD kidneys. Six of the ECD allografts were procured from DCD donors over the age of 60. Although, more donors in the older

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age group had hypertension or died due to cerebrovascular accidents, there was no significant difference in the presence of diabetes or elevated terminal creatinine between the two donor age groups.

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Mean recipient age was 53.8±14.7 years, and recipients of older DCD kidneys tended to be older as well (59.2 vs. 49.3 years). Median followup time was 21 months (range 1 to 87). Pulsatile perfusion was employed in 73 of 118 cases (62%). Cold ischemic time did not differ significantly between the two

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groups (652.6 ± 276.9 minutes vs. 718.1 ± 360.1, p=0.277). Similarly, there was no difference between the groups with respect to warm ischemic time (36.4 ± 25.5 minutes vs. 34.7 ± 24.8, p=0.706). Table 1

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shows the baseline characteristics of donors and recipients.

Immunosuppression

One hundred and eight allograft recipients received thymoglobulin and ten received basilixumab as

Outcomes

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induction therapy. Maintenance therapy consisted of tacrolimus, mycophenolic acid and prednisone.

Univariate analysis revealed that recipients of kidney transplants from DCD donors 51 years of age and

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greater demonstrated lower CrCl at 1 month, 3 months, and 12 months compared to those who received allografts from donors aged 50 years and under (50.3 ± 25.3 mL/min vs. 72.7 ± 31.7 mL/min at 1 month,

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p<0.001; 62.5 ± 22.9 mL/min vs. 87.9 ± 36.4 mL/min at 3 months, p<0.001; 66.2 ± 26.8 mL/min vs. 87.8 ± 38.7 mL/min at 12 months, p=0.013; Table 2; Figure 2). When ECD allografts were excluded from analysis, comparable results were observed (53.4 ± 24.4 mL/min vs. 72.7 ± 31.7 mL/min at 1 month, p=0.002; 61.6 ± 19.7 mL/min vs. 88.3 ± 35.6 mL/min at 3 months, p<0.001; 66.2 ± 26.8 mL/min vs. 87.8 ± 38.7 mL/min at 12 months, p=0.005, Table 2). Data was reanalyzed during the time periods of 20062009 and 2010-2013 in order to demonstrate whether older kidneys had improved function after greater

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experience with the donor operation and pulsatile perfusion had been obtained. Even in the later time period, the older donors had inferior graft function vs. younger donors at one year.

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DCD allografts from donors older than 50 years did not experience a higher rate of delayed graft function compared to those from donors 50 years of age or younger (57.4% vs 62.5%, p=0.706; Table 2). No patients experienced primary non-function of their graft. Moreover, there was no significant

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difference detected in graft loss at 1 year (9.3% vs. 7.8% for donors > 50 and donors ≤ 50 respectively, p=1.00; Table 2). Four of the ten graft failures in our cohort were observed among the ECD allografts,

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with two of these in recipients of kidneys from donors greater than 60 years of age. Three of the four ECD failures occurred within 1 year of transplantation.

Length of hospital stay was equivalent in both groups (13.8 ± 6.9 days vs. 13.9 ± 8.5 days for DCD donors >50 years vs. <50 years respectively, p=0.929). No difference was observed between the two

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age categories in terms of hospital readmissions related to the transplant (51.9% vs. 42.2% for DCD donors >50 years vs. <50 years respectively, p=0.355). In addition, the rate of cellular, antibody-mediated

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and mixed types of rejections did not differ significantly between the two groups (Table 2).

Multivariate regression analysis determined that donor age, recipient age, recipient sex, and cold

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ischemia time were independent predictors of CrCl at 12 months (Table 3). Recipients of DCD kidneys from donors over the age of 50 were more likely to experience reduced CrCl relative to those younger than 50 years. Decreased CrCl was also associated with increasing age of graft recipients. Furthermore, longer cold ischemia times tended to result in lower CrCl rates at 12 months.

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DISCUSSION Over the last decade, the average age of donors of DCD renal allografts has been increasing and has led to a greater number of transplantations with older grafts (4). Consequently, there is concern

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regarding the performance of these kidney transplants and whether or not they are acceptable for transplantation. Most groups that have examined donor age as a variable affecting DCD allograft outcomes have limited donor age to 60 years for fear of early graft failure and primary non-function

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(10,11). A previous study by Snoeijis had concluded that renal allografts from older DCD donors were not suitable for transplantation without preoperative biopsies and detailed assessment given higher rates

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of primary non-function, decreased graft survival and reduced GFR at 1 year (9). Despite their conclusions, the difference in these outcome variables did not reach statistical significance and the number of DCD donors was quite small in their study. Additionally, they compared donors aged older than 65 years to those younger than 65, providing conclusions based upon an older ECD donor cohort.

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Our institution performed a retrospective analysis to determine if a difference in outcomes exists between DCD allografts from donors over the age of 50 versus those 50 years of age and younger in order to provide quality assurance to our patients receiving slightly older DCD kidneys. In our study, recipients

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of DCD allografts from donors older than 50 years of age had statistically significant lower CrCl at 1 month, 3 months and 12 months than those who received kidneys from donors 50 years of age or

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younger. Our findings are supported by the findings of Thorton et al. that showed similar trends in their cohort of 136 DCD renal transplant recipients (12). It should be noted that recipients of older donor allografts tended to be older as well. This is a reflection of the algorithm used by our Organ Procurement Organization for organ allocation, in which younger kidneys (<35 years) were preferentially allocated to younger recipients (<55 years).

Despite decreased CrCl within the first 12 months in our study, this did not translate into greater rates of graft loss at 1 year. As 1 year renal function has been believed to reflect long-term graft loss (13),

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one would assume that long-term outcomes of the older DCD kidneys would be inferior vs. the younger cohort. This statement is in keeping with the knowledge that recipients of >50 year old NDD kidneys have inferior graft survival vs. recipients of <50 year old NDD kidneys as well (14). It must be cautioned

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that when the ECD/DCD cohort was assessed, graft failure was observed in 4 of the 14 grafts (28.6%). Three of these occurred within 1 year of transplantation and 2 were from donors older than 60 years of age. When ECD allografts were excluded from the analysis, we still observed similar trends in CrCl

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between the two groups at the same time points. However, given the small number of ECD kidneys in our

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cohort, firm conclusions regarding the performance of DCD/ECD kidneys could not be made.

In our cohort, recipients of DCD kidneys from donors greater than 50 years of age did not experience higher rates of DGF compared to those 50 years old or younger. This is in contrast to the findings by Locke et al., which reported a lower incidence of DGF in donors younger than 50 years compared with donors older than 50 years. This may simply reflect donor selection bias, differences in

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cold ischemic time and use of pulsatile perfusion.

For the first time, we have shown that transplanting kidneys from donors >50 does not

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significantly affect length of hospital stay, hospital readmissions, or rejections vs. the younger group. This provides reassurance to policy-makers that the utilization of this older organ source does not impact these

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clinical outcomes in already resource intensive transplant procedures that are associated with longer hospital stays, greater need for dialysis and procurement costs vs. NDD organ transplantation.

In addition to donor age, independent predictors of CrCl at 12 months from our multivariate

linear regression included recipient age, recipient sex, and cold ischemia time. With respect to recipient age, it is likely that reduced CrCl associated with increasing age reflects a general tendency of older patients to possess comorbid conditions and an overall inferior health status. Male recipients tended to exhibit greater CrCl rates at 12 months. This may be due to the fact that females tend to experience more

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immunologic conditions that may predispose to rejection or poor graft function. Increased cold ischemia time has been extensively shown to be a variable affecting delayed graft function and long-term graft

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survival as well (1,14,15).

There are a few important limitations to our work. This was a retrospective study, which limits our ability to control for unknown confounders. In addition, our results are based on findings of a single

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institution with a limited sample size, which may affect our ability to generalize the results, and therefore this study should be considered exploratory. However, this justifies the need for a larger prospective

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study. Moreover, analysis was performed for data up to 1 year post-transplant and reflects short-term outcomes. Further follow-up is required to examine the long-term outcomes and survival of these DCD allografts.

In conclusion, recipients of DCD renal allografts >50 years in this study had similar outcomes in

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terms of delayed graft function, length of hospital stay, hospital readmissions and rejections with younger DCD donors. Furthermore, graft survival was similar between the two groups at 1 year. As expected, creatinine clearance was reduced at 1 month, 3 months, and 12 months in recipients of DCD renal

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allografts from donors over the age of 50 compared with those from donors 50 years of age and younger. Fortunately, renal function was excellent at all time points in both groups. These results have promoted

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the authors to continue using older donors for DCD transplants, and although we are cautious about ECD grafts, we have not identified a clear age limit to DCD transplantation. Studies with a larger population and longer follow-up will provide more insight into the long-term durability of these grafts and their potential role in meeting the rising demands on the current donor organ pool.

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REFERENCES

1. Summers DM, Johnson RJ, Allen J, et al. Analysis of factors that affect outcome after transplantation

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of kidneys donated after cardiac death in the UK: a cohort study. Lancet, 2010, 376: 1303-11.

2. Weber M, Dindo D, Demartines N, et al. Kidney transplantation from donors without a heartbeat. N

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Engl J Med, 2002, 347: 248-55.

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3. Le Dinh H, Monard J, Delbouille MH, et al. A More Than 20% Increase in Deceased-Donor Organ Procurement and Transplantation Activity After the Use of Donation After Circulatory Death. Transplant Proc. 2014, 46: 9-13.

4. Wadei HM, Heckman MG, Rawal B, et al. Comparison of Kidney Function Between Donation After

81.

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Cardiac Death and Donation After Brain Death Kidney Transplantation. Transplantation, 2013, 96: 274-

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5. Klein AS, Messersmith EE, Ratner LE, et al. Organ Donation and Utilization in the United States,

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1999–2008. Am J Transplant, 2010, 10: 973-986.

6. Snoeijs MG, Winkens B, Heemskerk MB, et al. Kidney transplantation from donors after cardiac death: a 25-year experience. Transplantation, 2010, 90: 1106-12.

7. Nicholson ML, Metcalfe MS, White SA, et al. A comparison of the results of renal transplantation from non-heart-beating, conventional cadaveric, and living donors. Kidney Int, 2000, 58: 2585-91.

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8. Wijnen RM, Booster MH, Stubenitsky BM, et al. Outcome of transplantation of non-heart-beating donor kidneys. Lancet, 1995, 345: 1067-70.

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9. Snoeijs MG, Schaefer S, Christiaans MH, et al. Kidney Transplantation Using Elderly Non-Beating Donors: A Single-Center Experience. Am J Transplant, 2006, 6: 1066-71.

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10. Cecka, JM. The OPTN/UNOS renal transplant registry. Clin Trans, 2004, 1-16.

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11. Denecke C, Yuan X, Ge X, et al. Synergistic effects of prolonged warm ischemia and donor age on the immune response following donation after cardiac death kidney transplantation. Surgery, 2013, 153:249-61.

12. Thornton SR, Hamilton N, Evans D, et al. Outcome of Kidney Transplantation From Elderly Donors

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After Cardiac Death. Transplant Proc, 2011, 43: 3686-9.

13. Hariharan S, McBride MA, Cherikh WS, et al. Post-transplant renal function in the first year predicts

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long-term kidney transplant survival. Kidney Int, 2002, 62: 311-8.

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14. Locke JE, Segev DL, Warren DS, et al. Outcomes of kidneys from donors after cardiac death: implications for allocation and preservation. Am J Transplant, 2007, 7: 1797-807.

15. Kayler LK, Magliocca J, Zendejas I, et al. Impact of Cold Ischemia Time on Graft Survival Among ECD Transplant Recipients: A Paired Kidney Analysis. Am J Transplant, 2011, 11: 2647-56.

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Table 1. Baseline characteristics of donors and recipientsa

(n=118)

Donor age >50 (n=54)

Donors

Donor age ≤ 50 (n=64)

P value

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Overall

43.4 ± 14.6

56.2 ± 3.1

Men

81 (68.6%)

32 (59.2%)

Hypertension

20 (15.2%)

15 (27.8%)

Death from CVAb

28 (23.7%)

23 (42.6%)

5 (7.8%)

<0.001

Terminal creatinine > 1.5 mg/dL (>133 umol/L)

4 (3.4%)

0 (0%)

4 (6.3%)

0.124

Diabetes mellitus

4 (3.4%)

2 (3.7%)

2 (3.2%)

1.00

Expanded donor criteria

14 (11.9%)

14 (25.9%)

0 (0%)

<0.001

53.8 ± 14.7

59.2 ± 12.6

49.3 ± 14.9

<0.001

80 (67.8%)

37 (68.5%)

43 (67.2%)

1.00

33 (28.0%)

14 (25.9%)

19 (29.7%)

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Recipients

Men Cause of renal failure

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Glomerulonephritis

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Mean age (years)

32.6 ± 11.2

<0.001

49 (76.6%)

1.00

5 (7.8%)

0.006

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Mean age (years)

16 (13.6%)

11 (20.4%)

5 (7.8%)

0.06

Diabetic nephropathy

26 (22.0%)

11 (20.4%)

15 (23.4%)

0.82

Hypertension

19 (16.1%)

7 (13.0%)

12 (18.8%)

0.46

Other or unspecified

24 (20.3%)

11 (20.4%)

13 (20.3%)

1.00

688.1 ± 325.0

652.6 ± 276.9

718.1 ± 360.1

0.28

35.5 ± 25.1

36.4 ± 25.5

34.7 ± 24.8

0.71

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Polycystic kidney disease

Cold ischemia time (CIT) (minutes)

Warm ischemia time (WIT)

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a

Data are reported as the number (n) and percent (%) of patients experiencing the outcome. Mean age is expressed in years ± SD and CIT and WIT are expressed in minutes ± SD. b

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CVA: cerebrovascular accident

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Table 2. Univariate outcome assessmenta. Donor age >50 (n=54)

Donor age ≤ 50 (n=64)

P value

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Recipient creatinine clearance (mL/min) 25.2 ± 21.9

28.3 ± 29.0

0.454

1 month

50.3 ± 25.3

72.7 ± 31.7

<0.001

3 months

62.5 ± 22.9

87.9 ± 36.4

<0.001

12 months

66.2 ± 26.8

87.8 ± 38.7

0.013

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7 days

Recipient creatinine clearance with 14 ECD allografts excluded (mL/min)

22.6 ± 21.9

28.3 ± 29.0

0.204

1 month

53.4 ± 24.4

72.7 ± 31.7

0.002

3 months

61.6 ± 19.7

88.3 ± 35.6

<0.001

12 months

64.9 ± 15.4

87.9 ± 36.4

0.005

31 (57.4%)

40 (62.5%)

0.706

5 (9.3%)

5 (7.8%)

1.000

28 (51.9%)

27 (42.2%)

0.355

13.8 ± 6.9

13.9 ± 8.5

0.929

Cell-mediated rejection

8 (14.8%)

6 (9.4%)

0.403

Antibody-mediated rejection

1 (1.8%)

0 (0%)

0.458

1 (1.8%)

2 (3.1%)

1.000

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7 days

Graft failure

Readmissions

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Length of stay (days)

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DGF

Mixed rejection a

Data are reported as the number (n) and percent (%) of patients experiencing the outcome. Recipient creatinine clearance is reported as means ± SD. LOS is expressed as mean number of days ± SD.

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Table 3. Independent predictors of CrCl at 12 months based on multivariate linear regression Point estimate

CI

P-value

Donor age

-18.5a

[-34.48, -2.43]

0.025

Recipient age

-0.73b

[-1.22, -0.23]

0.005

Recipient sex

19.9c

[3.37, 36.39]

0.019

Cold ischemia time (CIT)

0.02d

[-0.002, 0.041]

0.081

b

change in CrCl per year of increased recipient age

c

average change in CrCl for male recipient sex

d

change in CrCl per minute of increased CIT

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average change in CrCl for donor age > 50

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a

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Variable

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Figure 1. DCD donor population.

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Figure 2. Post-transplantation creatinine clearance of recipients of DCD allografts at 7 days, 1 month, 3

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months and 12 months.

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Abbreviations CIT: cold ischemia time CrCl: creatinine clearance

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DCD: donation after cardiac death DGF: delayed graft function ECD: expanded donor criteria

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eGFR: estimated glomerular filtration rate LOS: length of stay

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NDD: determination of neurologic death

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WIT: warm ischemia time