Kidneys From Standard-Criteria Donors With Different Severities of Terminal Acute Kidney Injury C.C. Yua, H.C. Hoa,*, T.M. Yub, Y.C. Oua, K.H. Shub, C.L. Chenga, C.K. Sua, W.M. Chena, S.S. Wanga, C.S. Chena, J.R. Lia, and C.K. Yanga a Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan; and bDivision of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
ABSTRACT Objectives. High terminal serum creatinine level in a deceased donor has been reported as the second most frequent cause of refusal for kidney transplantation. A growing body of evidence has shown a comparable outcome of kidney transplantation from deceased donors with acute kidney injury (AKI). However, the influence of the severity of AKI on graft outcomes remains to be elucidated. Methods. In this retrospective cohort study, 84 consecutive kidney transplants from 57 standard-criteria donors were classified into 4 groups by RIFLE (Risk, Injury, Failure, Loss of function, and End-stage renal disease) classification according to donor AKI severity before kidney procurement. The donor and recipient characteristics and graft outcomes were compared. Results. Of 84 kidney transplants, 56, 11, 10, and 7 recipients were in the Non-AKI, Risk, Injury, and Failure groups. The mean terminal creatinine was 1.1, 1.6, 2.3, and 4.4 mg/dL in these 4 groups. However, the graft outcomes, including primary nonfunction rate, delayed graft function rate, acute rejection rate, renal function, graft survival and overall survival over the first 5 years had no statistical difference. A trend toward increasing delayed graft function rate as the severity of AKI increased was observed (Non-AKI, Risk, Injury, and Failure: 26.8%, 36.4%, 60.0%, and 57.1%, P ¼ .099). Conclusions. Our study demonstrates that AKI before procurement does not cause adverse long-term graft outcomes. Standard-criteria donors with AKI are suitable for kidney transplantation, even with a high severity of AKI.
K
IDNEY transplantation results in better quality of life and longer life expectancy than dialysis for patients with end-stage renal disease. The number of candidates for kidney transplantation increases continuously; however, the donor pool is relatively unchanged. The widening gap between supply and demand leads many transplant centers to use marginal donors, including expanded-criteria donors (ECDs), donation after cardiac death, dual-kidney transplantation, and as in this study, donors with acute kidney injury (AKI). AKI was thought to be a reversible condition, based on quickly reversible serum creatinine concentrations if the etiology is corrected. For donors with AKI, many transplant centers were concerned about whether the injured kidney could tolerate the hypoxic-ischemic and reperfusion injury
during transplantation; therefore, abnormal terminal serum creatinine had been reported as the second (22%) most frequent cause of kidney refusal [1]. In contrast, a growing body of evidence shows that kidneys from donors with AKI have similar long-term renal function and graft survival compared with kidneys from donors without AKI [2e7], and only higher delayed graft function (DGF) rate was concerned [4e7]. However, the optimal use of these injured kidneys has not yet been established. One of the concerns is the safety of using kidneys with a high severity of AKI. Therefore, we examined *Address correspondence to Hao-Chung Ho, No. 160, Section 3, Chung-Kang Road, Taichung, Taiwan, R. O. C. E-mail: [email protected]
ª 2014 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/14 http://dx.doi.org/10.1016/j.transproceed.2014.11.002
Transplantation Proceedings, 46, 3335e3338 (2014)
3335
3336
YU, HO, YU ET AL
the transplant outcomes of kidneys from different severities of AKI in this study. MATERIALS AND METHODS We retrospectively reviewed consecutive donors and recipients who underwent deceased-donor kidney transplantation at the Taichung Veterans General Hospital from 2005 to 2011. Two recipients who received dual kidney transplantation and 5 ECDs were excluded. ECDs refer to donors who are age >60 years or 50 to 59 years and have any 2 of the following criteria: hypertension, death from cerebrovascular accident, or admission serum creatinine >1.5 mg/dL. None of them had a positive cross-match test result, preemptive transplantation, or multiorgan transplantation. Finally, a total of 84 kidney transplants from 57 standard-criteria donors were enrolled. Donors and recipients were classified into 4 groups by RIFLE classification (Risk, Injury, Failure, Loss of function, and End-stage renal disease) [8] based on admission and terminal creatinine. Risk was defined when the terminal creatinine increased 1.5 times with respect to the admission creatinine, Injury was defined when it increased 2 times, Failure was defined when it increased 3 times, and the others belonged to the Non-AKI group. In addition, we also compared the Non-AKI group with the All-AKI group, which included all patients in Risk, Injury, and Failure groups. Upon procurement, we directly cannulated the aorta and vena cava during laparotomy rather than using femoral double balloon catheterization. After in situ perfusion with histidine-tryptophanketoglutarate solution and en-bloc excision, the bilateral kidneys were divided on bench and secondary perfusion was performed. If the kidney looked totally white with intact renal capsule and clear outflows from the renal vein, it was considered a useable graft. Because there was no machine perfusion available in Taiwan, all kidneys were only preserved by cold storage using histidinetryptophan-ketoglutarate solution. The zero-time graft biopsy was considered if donors had a higher severity of AKI or comorbidity. The initial immunosuppressive regimen included steroids, calcineurin inhibitors, and mycophenolic acid for most recipients and was adjusted at follow-up according to clinical condition.
Many variables of donors and recipients were assessed (Tables 1 and 2). For zero-time biopsy, the histological chronicity was assessed semiquantitatively by a biopsy-based scoring system for kidneys [9], with scores ranging from 0 (absence of renal lesions) to 12 (marked changes in the renal parenchyma). All recipients had at least 1 year of follow-up. The multiple variables of graft outcomes were evaluated (Table 3). In this study, primary nonfunction was defined as permanent loss of graft function immediately after transplantation, and DGF was defined as requirement of dialysis for initial impaired graft function. Acute rejection was defined as biopsy-proven acute rejection. Graft survival was defined as no graft failure or patient death. The estimated glomerular filtration rate (eGFR) was calculated by the Modification of Diet in Renal Disease formula for Chinese [10]. Recipients who required long-term dialysis after graft failure were excluded in the calculation of the mean creatinine and eGFR. Statistical analysis was performed using SPSS version 19 (SPSS Inc., Chicago, Illinois). Categorical variables were summarized using number and proportion compared by Pearson c2 or Fisher exact test. Continuous variables were summarized using the mean and standard deviation and compared by Mann-Whitney U test for 2 groups and Kruskal-Wallis test for more than 2 groups. The Kaplan-Meier method with log rank test was used for survival analysis. Data analysis was approved by the Institutional Review Board of the Taichung Veterans General Hospital (No. CE12330).
RESULTS
Of 57 deceased donors, 19 (33.3%) developed AKI before procurement, including 7 in the Risk group, 7 in the Injury group, and 5 in the Failure group. Donor characteristics of Non-AKI, Risk, Injury, and Failure groups are shown in Table 1. The mean admission creatinine was similar among groups (Non-AKI, Risk, Injury, and Failure: 0.9 0.27, 0.9 0.27, 1.0 0.40, and 1.1 0.22 mg/dL, P ¼ .588). The mean terminal creatinine was significantly different in these 4 groups (Non-AKI, Risk, Injury, and Failure: 1.1 0.32, 1.6 0.40, 2.3 0.83, and 4.4 1.72 mg/dL, P < .001). There were no significant differences among groups for
Table 1. Donor Characteristics
Age (y) Sex, male Diabetes Hypertension Cause of death Cerebrovascular accident Trauma Other Cardiopulmonary resuscitation Donation after cardiac death Admission creatinine (mg/dL) (range) Terminal creatinine (mg/dL) (range) Biopsy Acute tubular necrosis only Chronicity on histology Abbreviation: AKI, acute kidney injury. *P < .05.
Non-AKI (n ¼ 38)
Risk (n ¼ 7)
Injury (n ¼ 7)
Failure (n ¼ 5)
35 12.2 27 (71.1%) 0 (0.0%) 1 (2.6%)
41 11.0 6 (85.7%) 0 (0.0%) 2 (28.6%)
40 9.8 4 (57.1%) 1 (14.3%) 2 (28.6%)
35 13.9 4 (80.0%) 0 (0.0%) 1 (20.0%)
.515 .728 .333 .017*
10 (26.3%) 27 (71.1%) 1 (2.6%) 5 (13.2%) 1 (2.6%) 0.9 0.27 (0.5e1.5) 1.1 0.32 (0.5e1.6) 3 (7.9%) 2 0
3 (42.9%) 4 (57.1%) 0 (0.0%) 4 (57.1%) 2 (28.6%) 0.9 0.27 (0.6e1.4) 1.6 0.40 (1.1e2.1) 1 (14.3%) 0 1
2 (28.6%) 4 (57.1%) 1 (14.3%) 3 (42.9%) 1 (14.3%) 1.0 0.40 (0.6e1.5) 2.3 0.83 (1.6e3.6) 5 (71.4%) 2 2
2 (40.0%) 3 (60.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 1.1 0.22 (0.8e1.2) 4.4 1.72 (2.4e6.2) 3 (60.0%) 1 2
.639
P Value
.019* .079 .588
ABSTRACT Objectives. High terminal serum creatinine level in a deceased donor has been reported as the second most frequent cause of refusal for kidney transplantation. A growing body of evidence has shown a comparable outcome of kidney transplantation from deceased donors with acute kidney injury (AKI). However, the influence of the severity of AKI on graft outcomes remains to be elucidated. Methods. In this retrospective cohort study, 84 consecutive kidney transplants from 57 standard-criteria donors were classified into 4 groups by RIFLE (Risk, Injury, Failure, Loss of function, and End-stage renal disease) classification according to donor AKI severity before kidney procurement. The donor and recipient characteristics and graft outcomes were compared. Results. Of 84 kidney transplants, 56, 11, 10, and 7 recipients were in the Non-AKI, Risk, Injury, and Failure groups. The mean terminal creatinine was 1.1, 1.6, 2.3, and 4.4 mg/dL in these 4 groups. However, the graft outcomes, including primary nonfunction rate, delayed graft function rate, acute rejection rate, renal function, graft survival and overall survival over the first 5 years had no statistical difference. A trend toward increasing delayed graft function rate as the severity of AKI increased was observed (Non-AKI, Risk, Injury, and Failure: 26.8%, 36.4%, 60.0%, and 57.1%, P ¼ .099). Conclusions. Our study demonstrates that AKI before procurement does not cause adverse long-term graft outcomes. Standard-criteria donors with AKI are suitable for kidney transplantation, even with a high severity of AKI.
K
IDNEY transplantation results in better quality of life and longer life expectancy than dialysis for patients with end-stage renal disease. The number of candidates for kidney transplantation increases continuously; however, the donor pool is relatively unchanged. The widening gap between supply and demand leads many transplant centers to use marginal donors, including expanded-criteria donors (ECDs), donation after cardiac death, dual-kidney transplantation, and as in this study, donors with acute kidney injury (AKI). AKI was thought to be a reversible condition, based on quickly reversible serum creatinine concentrations if the etiology is corrected. For donors with AKI, many transplant centers were concerned about whether the injured kidney could tolerate the hypoxic-ischemic and reperfusion injury
during transplantation; therefore, abnormal terminal serum creatinine had been reported as the second (22%) most frequent cause of kidney refusal [1]. In contrast, a growing body of evidence shows that kidneys from donors with AKI have similar long-term renal function and graft survival compared with kidneys from donors without AKI [2e7], and only higher delayed graft function (DGF) rate was concerned [4e7]. However, the optimal use of these injured kidneys has not yet been established. One of the concerns is the safety of using kidneys with a high severity of AKI. Therefore, we examined *Address correspondence to Hao-Chung Ho, No. 160, Section 3, Chung-Kang Road, Taichung, Taiwan, R. O. C. E-mail: [email protected]
ª 2014 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/14 http://dx.doi.org/10.1016/j.transproceed.2014.11.002
Transplantation Proceedings, 46, 3335e3338 (2014)
3335
3336
YU, HO, YU ET AL
the transplant outcomes of kidneys from different severities of AKI in this study. MATERIALS AND METHODS We retrospectively reviewed consecutive donors and recipients who underwent deceased-donor kidney transplantation at the Taichung Veterans General Hospital from 2005 to 2011. Two recipients who received dual kidney transplantation and 5 ECDs were excluded. ECDs refer to donors who are age >60 years or 50 to 59 years and have any 2 of the following criteria: hypertension, death from cerebrovascular accident, or admission serum creatinine >1.5 mg/dL. None of them had a positive cross-match test result, preemptive transplantation, or multiorgan transplantation. Finally, a total of 84 kidney transplants from 57 standard-criteria donors were enrolled. Donors and recipients were classified into 4 groups by RIFLE classification (Risk, Injury, Failure, Loss of function, and End-stage renal disease) [8] based on admission and terminal creatinine. Risk was defined when the terminal creatinine increased 1.5 times with respect to the admission creatinine, Injury was defined when it increased 2 times, Failure was defined when it increased 3 times, and the others belonged to the Non-AKI group. In addition, we also compared the Non-AKI group with the All-AKI group, which included all patients in Risk, Injury, and Failure groups. Upon procurement, we directly cannulated the aorta and vena cava during laparotomy rather than using femoral double balloon catheterization. After in situ perfusion with histidine-tryptophanketoglutarate solution and en-bloc excision, the bilateral kidneys were divided on bench and secondary perfusion was performed. If the kidney looked totally white with intact renal capsule and clear outflows from the renal vein, it was considered a useable graft. Because there was no machine perfusion available in Taiwan, all kidneys were only preserved by cold storage using histidinetryptophan-ketoglutarate solution. The zero-time graft biopsy was considered if donors had a higher severity of AKI or comorbidity. The initial immunosuppressive regimen included steroids, calcineurin inhibitors, and mycophenolic acid for most recipients and was adjusted at follow-up according to clinical condition.
Many variables of donors and recipients were assessed (Tables 1 and 2). For zero-time biopsy, the histological chronicity was assessed semiquantitatively by a biopsy-based scoring system for kidneys [9], with scores ranging from 0 (absence of renal lesions) to 12 (marked changes in the renal parenchyma). All recipients had at least 1 year of follow-up. The multiple variables of graft outcomes were evaluated (Table 3). In this study, primary nonfunction was defined as permanent loss of graft function immediately after transplantation, and DGF was defined as requirement of dialysis for initial impaired graft function. Acute rejection was defined as biopsy-proven acute rejection. Graft survival was defined as no graft failure or patient death. The estimated glomerular filtration rate (eGFR) was calculated by the Modification of Diet in Renal Disease formula for Chinese [10]. Recipients who required long-term dialysis after graft failure were excluded in the calculation of the mean creatinine and eGFR. Statistical analysis was performed using SPSS version 19 (SPSS Inc., Chicago, Illinois). Categorical variables were summarized using number and proportion compared by Pearson c2 or Fisher exact test. Continuous variables were summarized using the mean and standard deviation and compared by Mann-Whitney U test for 2 groups and Kruskal-Wallis test for more than 2 groups. The Kaplan-Meier method with log rank test was used for survival analysis. Data analysis was approved by the Institutional Review Board of the Taichung Veterans General Hospital (No. CE12330).
RESULTS
Of 57 deceased donors, 19 (33.3%) developed AKI before procurement, including 7 in the Risk group, 7 in the Injury group, and 5 in the Failure group. Donor characteristics of Non-AKI, Risk, Injury, and Failure groups are shown in Table 1. The mean admission creatinine was similar among groups (Non-AKI, Risk, Injury, and Failure: 0.9 0.27, 0.9 0.27, 1.0 0.40, and 1.1 0.22 mg/dL, P ¼ .588). The mean terminal creatinine was significantly different in these 4 groups (Non-AKI, Risk, Injury, and Failure: 1.1 0.32, 1.6 0.40, 2.3 0.83, and 4.4 1.72 mg/dL, P < .001). There were no significant differences among groups for
Table 1. Donor Characteristics
Age (y) Sex, male Diabetes Hypertension Cause of death Cerebrovascular accident Trauma Other Cardiopulmonary resuscitation Donation after cardiac death Admission creatinine (mg/dL) (range) Terminal creatinine (mg/dL) (range) Biopsy Acute tubular necrosis only Chronicity on histology Abbreviation: AKI, acute kidney injury. *P < .05.
Non-AKI (n ¼ 38)
Risk (n ¼ 7)
Injury (n ¼ 7)
Failure (n ¼ 5)
35 12.2 27 (71.1%) 0 (0.0%) 1 (2.6%)
41 11.0 6 (85.7%) 0 (0.0%) 2 (28.6%)
40 9.8 4 (57.1%) 1 (14.3%) 2 (28.6%)
35 13.9 4 (80.0%) 0 (0.0%) 1 (20.0%)
.515 .728 .333 .017*
10 (26.3%) 27 (71.1%) 1 (2.6%) 5 (13.2%) 1 (2.6%) 0.9 0.27 (0.5e1.5) 1.1 0.32 (0.5e1.6) 3 (7.9%) 2 0
3 (42.9%) 4 (57.1%) 0 (0.0%) 4 (57.1%) 2 (28.6%) 0.9 0.27 (0.6e1.4) 1.6 0.40 (1.1e2.1) 1 (14.3%) 0 1
2 (28.6%) 4 (57.1%) 1 (14.3%) 3 (42.9%) 1 (14.3%) 1.0 0.40 (0.6e1.5) 2.3 0.83 (1.6e3.6) 5 (71.4%) 2 2
2 (40.0%) 3 (60.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 1.1 0.22 (0.8e1.2) 4.4 1.72 (2.4e6.2) 3 (60.0%) 1 2
.639
P Value
.019* .079 .588
