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.
Embargo Policy All article content is under embargo until uncorrected proof of the article becomes available online. We will provide journalists and editors with full-text copies of the articles in question prior to the embargo date so that stories can be adequately researched and written. The standard embargo time is 12:01 AM ET on that date. Questions regarding embargo should be directed to [email protected].
ACCEPTED MANUSCRIPT
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
1
Western University, Department of Surgery, Division of Urology
2
M AN U
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
2
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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 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, p50 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-
6
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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
RI PT
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.
SC
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
SC
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
EP
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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p133 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%)
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.
Embargo Policy All article content is under embargo until uncorrected proof of the article becomes available online. We will provide journalists and editors with full-text copies of the articles in question prior to the embargo date so that stories can be adequately researched and written. The standard embargo time is 12:01 AM ET on that date. Questions regarding embargo should be directed to [email protected].
ACCEPTED MANUSCRIPT
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
1
Western University, Department of Surgery, Division of Urology
2
M AN U
Keywords: Renal, transplant, organ donation, kidney, age
Abstract word count: 250 Article word count: 2468 Tables: 3
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EP
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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
1
ACCEPTED MANUSCRIPT
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
SC
Corinne Weernink Database maintenance
M AN U
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:
RI PT
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
2
ACCEPTED MANUSCRIPT
339 Windermere Road London, Ontario N6A 5A5
RI PT
Alp Sener London Health Sciences Centre 339 Windermere Road London, Ontario N6A 5A5
SC
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
3
ACCEPTED MANUSCRIPT
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
RI PT
intermediate-term outcomes. Materials & Methods: We compared recipient outcomes of DCD allografts from donors >50 years of age to those 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, p50 with two of the following:
TE D
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
EP
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.
AC C
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-
6
ACCEPTED MANUSCRIPT
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
RI PT
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
M AN U
cause’, and there were no protocol biopsies performed.
SC
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
TE D
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
AC C
RESULTS
EP
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
7
ACCEPTED MANUSCRIPT
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.
RI PT
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
SC
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
M AN U
shows the baseline characteristics of donors and recipients.
Immunosuppression
One hundred and eight allograft recipients received thymoglobulin and ten received basilixumab as
Outcomes
TE D
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
EP
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,
AC C
p133 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%)
