- Email: [email protected]
Study of Cadaveric Kidney Transplantation: A Single Center Experience
Study of Cadaveric Kidney Transplantation: A Single Center Experience Y. Kihara*, Y. Nakamura, T. Yokoyama, O. Konno, H. Iwamoto, and S. Kawachi Department of Digestive and Transplantation Surgery, Hachioji Medical Center, Tokyo Medical University, Tokyo, Japan
ABSTRACT Background. To increase the number of cadaveric kidney transplants in Japan, it is necessary to proactively perform transplantation from marginal donors. We had the opportunity to frequently perform kidney transplantation from expanded-criteria donors (ECDs), and it is anticipated that there will be increases in the number of ECD kidney transplants. Methods. In our institution, 18 patients underwent cadaveric kidney transplantation from January 2001 to December 2011. Sixteen of those patients were classified into 2 groups according to donation after brain death (BD) or after cardiac death (CD). We also classified donors as ECDs or standard-criteria donors (SCDs). Results. Kidney graft survival and engraftment were observed in all of the patients. Renal function at 1 year after transplantation was significantly better in the BD group than in the CD group. However, there was no significant difference between the groups in renal function at 3 and 5 years. Renal function at 1 and 3 years after transplantation was significantly better in the SCD group than in the ECD group, but there was no difference in renal function between the SDC and ECD groups at 5 years. Conclusions. The results were good for all of the patients. There are many reports that graft survival rate at 3e5 years after transplantation from ECDs is poorer than from SCDs. However, no statistically significant difference was found in kidney function at 5 years between the ECD and SCD groups in our patients.
T
HE RISING prevalence of chronic kidney disease (CKD) worldwide has dramatically increased the number of patients who start renal replacement therapy. Kidney transplantation has been proven to increase survival rates compared with dialysis. Previously, it had been thought that the only benefit of kidney transplantation was an improved quality of life, but now it is recognized to be a lifesaving procedure. Therefore, it is an urgent issue asd there has been an increase in the number of transplantations. Since the Revised Organ Transplant Law went into effect in Japan, the number of patients who undergo transplantation from brain-dead (BD) donors has increased. However, this does not mean that the total number of cadaveric kidney transplantation cases has increased, because these patients underwent transplantation from BD donors instead of cardiac-death (CD) donors after this law went into effect. To increase the number of cadaveric kidney transplantations in
ª 2016 Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
Transplantation Proceedings, 48, 725e728 (2016)
Japan, it is necessary to proactively perform transplantation from marginal donors as well. Currently in Japan, most transplants are from living kidney donors. At our center, we have had the opportunity to frequently perform kidney transplantation from expanded-criteria donors (ECDs), and it is anticipated that there will be an increase in the number of kidney transplants from ECDs. SUBJECTS AND METHODS In our institution, 18 patients underwent cadaveric kidney transplantation from January 2001 to December 2011. Of these patients,
*Address correspondence to Yu Kihara, Department of Digestive and Transplantation Surgery, Hachioji Medical Center, Tokyo Medical University, 1163, Tatemachi, Hachioji, Tokyo 1930998, Japan. E-mail: [email protected] 0041-1345/16 http://dx.doi.org/10.1016/j.transproceed.2015.12.091
725
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KIHARA, NAKAMURA, YOKOYAMA ET AL Table 1. Recipient Characteristics
Num
Graft
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
CD CD CD BD CD CD CD BD CD CD CD CD CD CD BD CD
Diag
IgA PCK MGN CGN unknown CGN MPGN CGN CGN PCK CGN unknown MPGN CGN CGN FGS
PreTx
ECD
1
1
1
1 1
1 1 1
1
R/Ag
D/Ag
HD
HLA MM
D-Cr
WIT
TIT
ATN
R-Cr
32 57 58 53 51 68 31 57 36 59 52 56 46 61 66 57
38 59 27 49 47 73 61 38 43 31 62 51 62 45 23 56
9y 5y 21y 20y 22y 22y 12y 28y 17y 27y 24y 13y 20y 18y 18y 12y
2 1 3 3 4 2 3 1 1 3 2 2 2 2 1 3
3.08 1.7 2.5 0.5 0.6 1.56 1.22 0.64 3.41 3.3 3.36 0.26 0.61 3.05 0.49 4.7
2 1 30 0 1 1 47 0 2 29 26 2 14 2 0 1
412 487 427 183 309 659 1474 342 498 1012 724 427 932 284 399 625
8 7 4 0 7 6 25 0 4 9 34 0 1 6 0 3
1 0.9 1.7 0.7 1.3 1.52 2.46 0.7 0.54 0.89 3.06 1.23 1.23 0.95 0.62 1.21
Immune Therapy (Initial)
NEOþMPSLþMMFþALG PRGþMPSLþMMFþALG PRGþMPSLþMMFþBX PRGþMPSLþMMFþBx NEOþMPSLþMMFþBx PRGþMPSLþMMFþBx PRGþMPSLþMMFþBx PRGþMPSLþMMFþBx PRGþMPSLþMMFþBx NEOþMPSLþMMFþBx GRCþMPSLþMMFþBx NEOþMPSLþMMFþBx GRCþMPSLþMMFþBx NEOþMPSLþMMFþBx PRGþMPSLþMMFþBx NEOþMPSLþMMFþBx
Abbreviations: Tx, transplantation; ECD, expanded criteria donor; R/Ag, recipient age; D/Ag, donor age; HD, hemodialysis; HLA MM, HLA mismatch; D-Cr, donor creatinine; R-Cr, recipient creatinine; WIT, warm ischemic time; TIT, total ischemic time; ATN, acute tubular necrosis; CD, cardiac death; BD, brain death; PCK, polycystic kidney.
16 patients (excluding 2 patients) were classified into 2 groups according to whether they had received a donation after BD (3 cases) or CD (13 cases). We also classified the patients into groups based on whether their donor was an ECD (7 cases) or a standardcriteria donor (SCD; 9 cases). For all recipients of cadaveric renal transplants, we obtained the following data: demographic information, age, sex, weight (kg), time on hemodialysis (HD), underlying disease, HLA compatibilities, cold ischemia time, immunosuppression at the initial time of transplantation, delayed graft function, serum creatinine (Cr) at 1, 3, and 5 years after transplantation, and graft and recipient survivals 5 years after transplantation. Statistical analysis was performed with the use of IBM SPSS statistics 22 software. The statistical analysis used Student t test for differences between the variables. Values of P < .05 were considered to be statistically significant.
The results of the comparison between the CD and BD groups are presented in Tables 3 and 4. Result 1 is the course of the patient in the hospital, and Result 2 comprises the complications and renal function after hospital discharge. For warm ischemia time and total ischemia time (TIT), the BD group had 0 minutes and 308 112 minutes, respectively, although the CD group had 12.2 minutes and 370 406 minutes, respectively. Immediate graft function was observed in all patients in the BD group and in 2 patients in the CD group. In the CD group, delayed graft function was observed in 11 patients, and the duration of acute tubular necrosis (ATN) was an average of 8.7 9.4 days. Renal functions after transplantation at discharge Table 2. Background CD vs BD
RESULTS
Our cadaveric kidney transplantation cases consisted of 3 patients in the BD group and 13 patients in the CD group. The demographics of the 16 patients are listed in Table 1. We first used the immunosuppressive agents calcineurin inhibitor, methylprednisolone, mycophenolate mofetil, and basiliximab. Only for 2 cases did we use antilymphocyte globulin instead of basiliximab. We compared the backgrounds of the CD and BD groups (Table 2). The donor Cr was higher in the CD group. There was a significant difference between groups for HD period and HLA mismatch. The mean ages of recipients were 58.7 years and 51.1 years in the BD and CD groups, respectively. The mean ages of donors were 36.7 10.7 years and 50.4 0.08 years in the BD and CD groups, respectively. Cr levels of the donors were 0.54 0.08 mg/dL and 2.26 1.36 mg/dL in the BD and CD groups, respectively. Various diseases in the CD group caused the renal insufficiency, but chronic glomerulonephritis (CGN) occurred only in the BD group. In the CD group, 6 ECDs were included.
Underlying disease CGN PCK MPGN MN IgAN FGS Unknown R/Age R/Gender D/Age D-Cr (mg/dL) Previous Tx ECD HLA-MM HD duration (month)
CD (n ¼ 13)
BD (n ¼ 3)
4 2 2 1 1 1 2 51.1 11.6 M:10 F:3 50.4 13.5 2.26 1.36 2 7 2.3 210.8 75.9
3 0 0 0 0 0 0 58.6 6.7 F:3 36.7 0.54 0.08 0 0 2.67 271 65.3
P Value
NS .013 NS .026
NS NS
Abbreviations: PCK, polycystic kidney; MGN, membranous glomerulonephritis; CGN, chronic glomerulonephritis; FGS, focal glomerulosclerosis; MN, membranous nephropathy; IgAN, IgA nephropathy; R/Age, recipient age; D/Age, donor age; R/Gender, recipient gender; Tx, transplantation; D-Cr, donorcreatinine; ECD, expanded criteria donor; HLA-MM, HLA mismatch; HD, hemodialysis.
CADAVERIC KIDNEY TRANSPLANTATION
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Table 3. Result 1: CD vs BD
WIT (min) TIT (min) CNI PRG NEO GRC IGF ATN (day) HD after Tx (times) R-Cr (mg/dL)
Table 5. Background: ECD vs SCD
CD (n ¼ 13)
BD (n ¼ 3)
P Value
12.2 15.6 636.2 335.3
0 308 111.9
.007
5 6 2 2 (15.4%) 11 cases 8.8 9.4 12 cases 3.5 2.8 1.38 0.69
3 0 0 3 (100%) 0 0 0 0 0.67 0.05
.001
Abbreviations: WIT, warm ischemic time; TIT, total ischemic time; CNI, calcineurin inhibitor; PRG, prograf (tacrolimus/twice daily administration); GRC, graceptor(tacrolimus/once daily administration); NEO, neoral (cyclosporine); IGF, immediate graft function; ATN, acute tubular necrosis; HD, hemodialysis; R-Cr, recipient creatinine; R/Age, recipient age; D/Age, donor age; R/Gender, recipient gender; Tx, transplantation; D-Cr, donorcreatinine; ECD, expanded criteria donor; HLA-MM, HLA mismatch; HD, hemodialysis.
were 0.67 0.05 mg/dL and 1.38 0.69 mg/dL in the BD and CD groups, respectively. Renal functions at 1 and 3 years after transplantation was 0.74 mg/dL and 0.77 mg/dL compared with 1.00 mg/dL and 0.98 mg/dL n the BD and CD groups, respectively. Rejection was observed in 2 patients in the CD group. One patient in the CD group was infected with cytomegalovirus after the transplantation. In the CD group, the donors tended to be younger than the recipients, but a reverse trend was found in the BD group. ATN was observed in 87% of the patients in the CD group, and its duration was an average of 8.8 9.4 days. No patients experienced primary nonfunction. We also examined the data for ECDs versus SCDs (Tables 5 and 6). Significant differences were observed for HD period, donor age, TIT, graft volume, ATN period, and Cr at 6, 12, and 36 months after renal transplantation. Renal functions at 1, 3, and 5 years, respectively, after transplantation were 1.51, 1.40, and 1.37 mg/dL in the ECD group compared with 1.00, 0.88, and 0.94 mg/dL in the SCD group. The ECD group had a significantly extended ATN Table 4. Result 2 for CD vs BD
PNF Rejection Bacteria CMV VZV Fungus Malignant CVD Return HD Cr 1Y Cr 3Y Cr 5Y
CD (n ¼ 13)
BD (n ¼ 3)
P Value
0 2 3 1 3 3 0 3 0 1.29 0.39 1.01 0.53 (n ¼ 13) 1.16 0.47 (n ¼ 7)
0 0 0 0 2 0 0 0 0 0.71 0.15 0.78 0.25 (n ¼ 2) 0.80 0.18 (n ¼ 2)
NS NS NS NS NS NS NS NS NS .001 NS NS
Abbreviations: PNF, primary nonfunction; CMV, cytomegalovirus; VZV, varicella zoster virus; CVD, cardio vascular disease; HD, hemodialysis; Cr, creatinine.
ECD (n ¼ 7)
R/Age HLA MM BMI HD duration (M) D/Age D-Cr (mg/dL) WIT (min) TIT (min) Graft Volume (g)
52.4 2.1 19.3 191.6 60.6 1.92 13.1 761.1 246.4
11.5 0.7 1.7 79.1 6.8 1.58 17.1 354.6 80.2
SCD (n ¼ 9)
52.6 2.2 18.8 245.3 37.9 1.95 7.3 429.6 181.9
11.4 1.1 3.5 68.4 9.2 1.35 12.6 237 47.8
P Value
NS NS NS .083 .00041 NS NS .029 .045
Abbreviations: R/Age, recipient age; HLA-MM, HLA mismatch; HD, hemodialysis; D/Age, donor age; D-Cr, donorcreatinine; WIT, warm ischemic time; TIT, total ischemic time.
duration. Renal function at 1 year after transplantation was significantly better in the BD group than in the CD group. However, there was no significant difference between groups in renal function at 3 and 5 years. Renal functions at 1 and 3 years after transplantation were significantly better in the SCD group than in the ECD group, but there was no difference in renal function at 5 years between the SDC and ECD groups. DISCUSSION
A total of 18 cadaveric kidney transplantations were performed at our center, and kidney graft survival and engraftment were observed in all patients. We know that the number of cases is small. However, Japan has fewer transplantations compared with other countries. Although kidney function after transplantation was better in the BD group, kidney graft survival and engraftment were observed in all patients in both groups. It has been reported that graft survival rate is poor in kidneys from ECDs compared with SCDs [1e5] and that kidney transplants with grafts from ECDs have significantly worse outcomes with higher rates of delayed graft function and acute rejection [3]. On the other hand, the reported rates of complications in recipients of ECD and SCD kidneys are similar [6], and transplantation of ECD kidneys has acceptable clinical and financial consequences in primary transplant recipients [7,8]. In our series, graft survival rates were significantly better only in allograft recipients from SCDs at 5 years of followup. At 1, 3, and 10 years, graft survival rates were similar between recipients from SCDs and ECDs. These results are Table 6. Kidney Function: ECD vs SCD
ATN (day) IGF R-Cr (Tx) R-Cr (6M) R-Cr (1Y) R-Cr (3Y) R-Cr (5Y)
ECD (n ¼ 7)
SCD (n ¼ 8)
P Value
10.9 13.2 2 (28.5%) 9.16 2.87 1.59 0.44 1.51 0.37 1.40 0.50 1.37 0.63
4.2 3.6 3 (37.5%) 7.75 3.18 1.00 0.37 1.00 0.37 0.88 0.23 0.94 0.28
.08 NS NS .0056 .0029 .0013 NS
Abbreviations: ATN, acute tubular necrosis; IGF, immediate graft function; R-Cr, recipient creatinine; Tx, transplantation.
728
in accordance with similar studies and United Network for Organ Sharing (UNOS) data [2,9]. In our patients, there was no significant difference between the groups. The results were good in all patients. Compared with the CD group, the mean age of donors tended to be lower and the recipient’s age tended to be higher in the BD group. ATN was observed in 87% of patients in the CD group, and its duration was an average of 8.8 9.4 days. The ECD group had significantly extended ATN duration. Kidney function at 1 year after transplantation was significantly better in the BD group compared with the CD group. However, there was no significant difference between groups in kidney function at 3 and 5 years. Kidney function at 1 and 3 years after transplantation was significantly better in the SCD group than in the ECD group, although there was no difference between the groups in renal function at 5 years. There have been many reports stating that graft survival rate at 3e5 years after transplantation from ECDs is poor compared with SCDs. Aubert et al reported that compared with SCDs, the graft survival rate after 7 years from ECDs was lower (88% vs 80%; P < .001), and prognostic determinants of ECD transplants were donor-specific antiHLA antibodies and cold ischemia time [1]. Papachristou et al reported that patient survival after ECD is similar to that after SCD but graft survival is significantly lower. However, because the renal function of recipients from ECD is adequate for a long period, the grafts from ECDs could be used in older patients [2]. However, in our patients, no statistically significant difference between the ECD and SCD groups was found in kidney function after 5 years. Our study suggests the potential to achieve good performance even in ECD kidneys. We would like to continue research this topic in the future. CONCLUSION
In our patients, there was no significant difference between patient outcomes after receiving transplants from
KIHARA, NAKAMURA, YOKOYAMA ET AL
ECDs or SCDs. Therefore, the recipients’ quality of life was improved by receiving kidneys from ECDs. Owing to the low donor pool in Japan, we think that actively using ECD kidneys will increase the number of renal transplantations. REFERENCES [1] Aubert O, Kamar N, Vernerey D, Viglietti D, Martinez F, Duong-Van-Huyen JP, et al. Long term outcomes of transplantation using kidneys from expanded criteria donors: prospective, population based cohort study. BMJ 2015;351:h3557. [2] 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;46:3172e4. [3] Ferrer F, Mota A, Alves R, Bastos C, Macário F, Figueiredo A, et al. Renal transplantation with expanded criteria donors: the experience of one Portuguese center. Transplant Proc 2009;41:791e3. [4] Schnitzler MA, Whiting JF, Brennan DC, Lin G, Chapman W, Lowell J, et al. The expanded criteria donor dilemma in cadaveric renal transplantation. Transplantation 2003;75:1940e5. [5] Hassanain M, Tchervenkov J, Cantarovich M, Metrakos P, Paraskevas S, Keith D, et al. Delayed graft function has an equally bad impact on deceased donor renal graft survival in both standard criteria donors and expanded criteria donors. Transplant Proc 2009;41:133e4. [6] Domagala P, Kwiatkowski A, Wszola M, Czerwinski J, Cybula K, Trzebicki J, et al. Complications of transplantation of kidneys from expanded-criteria donors. Transplant Proc 2009;41: 2970e1. [7] Sellers MT, Velidedeoglu E, Bloom RD, Grossman RA, Markmann JW, Naji A, et al. Expanded-criteria donor kidneys: a single-center clinical and short-term financial analysisdcause for concern in retransplantation. Transplantation 2004;78:1670e5. [8] Ratner LE, Kraus E, Magnuson T, Bender JS. Transplantation of kidneys from expanded criteria donors. Surgery 1996;119:372e7. [9] Heuer M, Zeiger A, Kaiser GM, Mathé Z, Goldenberg A, Sauerland S, et al. Use of marginal organs in kidney transplantation for marginal recipients: too close to the margins of safety? Eur J Med Res 2010;15:31e4.
ABSTRACT Background. To increase the number of cadaveric kidney transplants in Japan, it is necessary to proactively perform transplantation from marginal donors. We had the opportunity to frequently perform kidney transplantation from expanded-criteria donors (ECDs), and it is anticipated that there will be increases in the number of ECD kidney transplants. Methods. In our institution, 18 patients underwent cadaveric kidney transplantation from January 2001 to December 2011. Sixteen of those patients were classified into 2 groups according to donation after brain death (BD) or after cardiac death (CD). We also classified donors as ECDs or standard-criteria donors (SCDs). Results. Kidney graft survival and engraftment were observed in all of the patients. Renal function at 1 year after transplantation was significantly better in the BD group than in the CD group. However, there was no significant difference between the groups in renal function at 3 and 5 years. Renal function at 1 and 3 years after transplantation was significantly better in the SCD group than in the ECD group, but there was no difference in renal function between the SDC and ECD groups at 5 years. Conclusions. The results were good for all of the patients. There are many reports that graft survival rate at 3e5 years after transplantation from ECDs is poorer than from SCDs. However, no statistically significant difference was found in kidney function at 5 years between the ECD and SCD groups in our patients.
T
HE RISING prevalence of chronic kidney disease (CKD) worldwide has dramatically increased the number of patients who start renal replacement therapy. Kidney transplantation has been proven to increase survival rates compared with dialysis. Previously, it had been thought that the only benefit of kidney transplantation was an improved quality of life, but now it is recognized to be a lifesaving procedure. Therefore, it is an urgent issue asd there has been an increase in the number of transplantations. Since the Revised Organ Transplant Law went into effect in Japan, the number of patients who undergo transplantation from brain-dead (BD) donors has increased. However, this does not mean that the total number of cadaveric kidney transplantation cases has increased, because these patients underwent transplantation from BD donors instead of cardiac-death (CD) donors after this law went into effect. To increase the number of cadaveric kidney transplantations in
ª 2016 Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
Transplantation Proceedings, 48, 725e728 (2016)
Japan, it is necessary to proactively perform transplantation from marginal donors as well. Currently in Japan, most transplants are from living kidney donors. At our center, we have had the opportunity to frequently perform kidney transplantation from expanded-criteria donors (ECDs), and it is anticipated that there will be an increase in the number of kidney transplants from ECDs. SUBJECTS AND METHODS In our institution, 18 patients underwent cadaveric kidney transplantation from January 2001 to December 2011. Of these patients,
*Address correspondence to Yu Kihara, Department of Digestive and Transplantation Surgery, Hachioji Medical Center, Tokyo Medical University, 1163, Tatemachi, Hachioji, Tokyo 1930998, Japan. E-mail: [email protected] 0041-1345/16 http://dx.doi.org/10.1016/j.transproceed.2015.12.091
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KIHARA, NAKAMURA, YOKOYAMA ET AL Table 1. Recipient Characteristics
Num
Graft
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
CD CD CD BD CD CD CD BD CD CD CD CD CD CD BD CD
Diag
IgA PCK MGN CGN unknown CGN MPGN CGN CGN PCK CGN unknown MPGN CGN CGN FGS
PreTx
ECD
1
1
1
1 1
1 1 1
1
R/Ag
D/Ag
HD
HLA MM
D-Cr
WIT
TIT
ATN
R-Cr
32 57 58 53 51 68 31 57 36 59 52 56 46 61 66 57
38 59 27 49 47 73 61 38 43 31 62 51 62 45 23 56
9y 5y 21y 20y 22y 22y 12y 28y 17y 27y 24y 13y 20y 18y 18y 12y
2 1 3 3 4 2 3 1 1 3 2 2 2 2 1 3
3.08 1.7 2.5 0.5 0.6 1.56 1.22 0.64 3.41 3.3 3.36 0.26 0.61 3.05 0.49 4.7
2 1 30 0 1 1 47 0 2 29 26 2 14 2 0 1
412 487 427 183 309 659 1474 342 498 1012 724 427 932 284 399 625
8 7 4 0 7 6 25 0 4 9 34 0 1 6 0 3
1 0.9 1.7 0.7 1.3 1.52 2.46 0.7 0.54 0.89 3.06 1.23 1.23 0.95 0.62 1.21
Immune Therapy (Initial)
NEOþMPSLþMMFþALG PRGþMPSLþMMFþALG PRGþMPSLþMMFþBX PRGþMPSLþMMFþBx NEOþMPSLþMMFþBx PRGþMPSLþMMFþBx PRGþMPSLþMMFþBx PRGþMPSLþMMFþBx PRGþMPSLþMMFþBx NEOþMPSLþMMFþBx GRCþMPSLþMMFþBx NEOþMPSLþMMFþBx GRCþMPSLþMMFþBx NEOþMPSLþMMFþBx PRGþMPSLþMMFþBx NEOþMPSLþMMFþBx
Abbreviations: Tx, transplantation; ECD, expanded criteria donor; R/Ag, recipient age; D/Ag, donor age; HD, hemodialysis; HLA MM, HLA mismatch; D-Cr, donor creatinine; R-Cr, recipient creatinine; WIT, warm ischemic time; TIT, total ischemic time; ATN, acute tubular necrosis; CD, cardiac death; BD, brain death; PCK, polycystic kidney.
16 patients (excluding 2 patients) were classified into 2 groups according to whether they had received a donation after BD (3 cases) or CD (13 cases). We also classified the patients into groups based on whether their donor was an ECD (7 cases) or a standardcriteria donor (SCD; 9 cases). For all recipients of cadaveric renal transplants, we obtained the following data: demographic information, age, sex, weight (kg), time on hemodialysis (HD), underlying disease, HLA compatibilities, cold ischemia time, immunosuppression at the initial time of transplantation, delayed graft function, serum creatinine (Cr) at 1, 3, and 5 years after transplantation, and graft and recipient survivals 5 years after transplantation. Statistical analysis was performed with the use of IBM SPSS statistics 22 software. The statistical analysis used Student t test for differences between the variables. Values of P < .05 were considered to be statistically significant.
The results of the comparison between the CD and BD groups are presented in Tables 3 and 4. Result 1 is the course of the patient in the hospital, and Result 2 comprises the complications and renal function after hospital discharge. For warm ischemia time and total ischemia time (TIT), the BD group had 0 minutes and 308 112 minutes, respectively, although the CD group had 12.2 minutes and 370 406 minutes, respectively. Immediate graft function was observed in all patients in the BD group and in 2 patients in the CD group. In the CD group, delayed graft function was observed in 11 patients, and the duration of acute tubular necrosis (ATN) was an average of 8.7 9.4 days. Renal functions after transplantation at discharge Table 2. Background CD vs BD
RESULTS
Our cadaveric kidney transplantation cases consisted of 3 patients in the BD group and 13 patients in the CD group. The demographics of the 16 patients are listed in Table 1. We first used the immunosuppressive agents calcineurin inhibitor, methylprednisolone, mycophenolate mofetil, and basiliximab. Only for 2 cases did we use antilymphocyte globulin instead of basiliximab. We compared the backgrounds of the CD and BD groups (Table 2). The donor Cr was higher in the CD group. There was a significant difference between groups for HD period and HLA mismatch. The mean ages of recipients were 58.7 years and 51.1 years in the BD and CD groups, respectively. The mean ages of donors were 36.7 10.7 years and 50.4 0.08 years in the BD and CD groups, respectively. Cr levels of the donors were 0.54 0.08 mg/dL and 2.26 1.36 mg/dL in the BD and CD groups, respectively. Various diseases in the CD group caused the renal insufficiency, but chronic glomerulonephritis (CGN) occurred only in the BD group. In the CD group, 6 ECDs were included.
Underlying disease CGN PCK MPGN MN IgAN FGS Unknown R/Age R/Gender D/Age D-Cr (mg/dL) Previous Tx ECD HLA-MM HD duration (month)
CD (n ¼ 13)
BD (n ¼ 3)
4 2 2 1 1 1 2 51.1 11.6 M:10 F:3 50.4 13.5 2.26 1.36 2 7 2.3 210.8 75.9
3 0 0 0 0 0 0 58.6 6.7 F:3 36.7 0.54 0.08 0 0 2.67 271 65.3
P Value
NS .013 NS .026
NS NS
Abbreviations: PCK, polycystic kidney; MGN, membranous glomerulonephritis; CGN, chronic glomerulonephritis; FGS, focal glomerulosclerosis; MN, membranous nephropathy; IgAN, IgA nephropathy; R/Age, recipient age; D/Age, donor age; R/Gender, recipient gender; Tx, transplantation; D-Cr, donorcreatinine; ECD, expanded criteria donor; HLA-MM, HLA mismatch; HD, hemodialysis.
CADAVERIC KIDNEY TRANSPLANTATION
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Table 3. Result 1: CD vs BD
WIT (min) TIT (min) CNI PRG NEO GRC IGF ATN (day) HD after Tx (times) R-Cr (mg/dL)
Table 5. Background: ECD vs SCD
CD (n ¼ 13)
BD (n ¼ 3)
P Value
12.2 15.6 636.2 335.3
0 308 111.9
.007
5 6 2 2 (15.4%) 11 cases 8.8 9.4 12 cases 3.5 2.8 1.38 0.69
3 0 0 3 (100%) 0 0 0 0 0.67 0.05
.001
Abbreviations: WIT, warm ischemic time; TIT, total ischemic time; CNI, calcineurin inhibitor; PRG, prograf (tacrolimus/twice daily administration); GRC, graceptor(tacrolimus/once daily administration); NEO, neoral (cyclosporine); IGF, immediate graft function; ATN, acute tubular necrosis; HD, hemodialysis; R-Cr, recipient creatinine; R/Age, recipient age; D/Age, donor age; R/Gender, recipient gender; Tx, transplantation; D-Cr, donorcreatinine; ECD, expanded criteria donor; HLA-MM, HLA mismatch; HD, hemodialysis.
were 0.67 0.05 mg/dL and 1.38 0.69 mg/dL in the BD and CD groups, respectively. Renal functions at 1 and 3 years after transplantation was 0.74 mg/dL and 0.77 mg/dL compared with 1.00 mg/dL and 0.98 mg/dL n the BD and CD groups, respectively. Rejection was observed in 2 patients in the CD group. One patient in the CD group was infected with cytomegalovirus after the transplantation. In the CD group, the donors tended to be younger than the recipients, but a reverse trend was found in the BD group. ATN was observed in 87% of the patients in the CD group, and its duration was an average of 8.8 9.4 days. No patients experienced primary nonfunction. We also examined the data for ECDs versus SCDs (Tables 5 and 6). Significant differences were observed for HD period, donor age, TIT, graft volume, ATN period, and Cr at 6, 12, and 36 months after renal transplantation. Renal functions at 1, 3, and 5 years, respectively, after transplantation were 1.51, 1.40, and 1.37 mg/dL in the ECD group compared with 1.00, 0.88, and 0.94 mg/dL in the SCD group. The ECD group had a significantly extended ATN Table 4. Result 2 for CD vs BD
PNF Rejection Bacteria CMV VZV Fungus Malignant CVD Return HD Cr 1Y Cr 3Y Cr 5Y
CD (n ¼ 13)
BD (n ¼ 3)
P Value
0 2 3 1 3 3 0 3 0 1.29 0.39 1.01 0.53 (n ¼ 13) 1.16 0.47 (n ¼ 7)
0 0 0 0 2 0 0 0 0 0.71 0.15 0.78 0.25 (n ¼ 2) 0.80 0.18 (n ¼ 2)
NS NS NS NS NS NS NS NS NS .001 NS NS
Abbreviations: PNF, primary nonfunction; CMV, cytomegalovirus; VZV, varicella zoster virus; CVD, cardio vascular disease; HD, hemodialysis; Cr, creatinine.
ECD (n ¼ 7)
R/Age HLA MM BMI HD duration (M) D/Age D-Cr (mg/dL) WIT (min) TIT (min) Graft Volume (g)
52.4 2.1 19.3 191.6 60.6 1.92 13.1 761.1 246.4
11.5 0.7 1.7 79.1 6.8 1.58 17.1 354.6 80.2
SCD (n ¼ 9)
52.6 2.2 18.8 245.3 37.9 1.95 7.3 429.6 181.9
11.4 1.1 3.5 68.4 9.2 1.35 12.6 237 47.8
P Value
NS NS NS .083 .00041 NS NS .029 .045
Abbreviations: R/Age, recipient age; HLA-MM, HLA mismatch; HD, hemodialysis; D/Age, donor age; D-Cr, donorcreatinine; WIT, warm ischemic time; TIT, total ischemic time.
duration. Renal function at 1 year after transplantation was significantly better in the BD group than in the CD group. However, there was no significant difference between groups in renal function at 3 and 5 years. Renal functions at 1 and 3 years after transplantation were significantly better in the SCD group than in the ECD group, but there was no difference in renal function at 5 years between the SDC and ECD groups. DISCUSSION
A total of 18 cadaveric kidney transplantations were performed at our center, and kidney graft survival and engraftment were observed in all patients. We know that the number of cases is small. However, Japan has fewer transplantations compared with other countries. Although kidney function after transplantation was better in the BD group, kidney graft survival and engraftment were observed in all patients in both groups. It has been reported that graft survival rate is poor in kidneys from ECDs compared with SCDs [1e5] and that kidney transplants with grafts from ECDs have significantly worse outcomes with higher rates of delayed graft function and acute rejection [3]. On the other hand, the reported rates of complications in recipients of ECD and SCD kidneys are similar [6], and transplantation of ECD kidneys has acceptable clinical and financial consequences in primary transplant recipients [7,8]. In our series, graft survival rates were significantly better only in allograft recipients from SCDs at 5 years of followup. At 1, 3, and 10 years, graft survival rates were similar between recipients from SCDs and ECDs. These results are Table 6. Kidney Function: ECD vs SCD
ATN (day) IGF R-Cr (Tx) R-Cr (6M) R-Cr (1Y) R-Cr (3Y) R-Cr (5Y)
ECD (n ¼ 7)
SCD (n ¼ 8)
P Value
10.9 13.2 2 (28.5%) 9.16 2.87 1.59 0.44 1.51 0.37 1.40 0.50 1.37 0.63
4.2 3.6 3 (37.5%) 7.75 3.18 1.00 0.37 1.00 0.37 0.88 0.23 0.94 0.28
.08 NS NS .0056 .0029 .0013 NS
Abbreviations: ATN, acute tubular necrosis; IGF, immediate graft function; R-Cr, recipient creatinine; Tx, transplantation.
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in accordance with similar studies and United Network for Organ Sharing (UNOS) data [2,9]. In our patients, there was no significant difference between the groups. The results were good in all patients. Compared with the CD group, the mean age of donors tended to be lower and the recipient’s age tended to be higher in the BD group. ATN was observed in 87% of patients in the CD group, and its duration was an average of 8.8 9.4 days. The ECD group had significantly extended ATN duration. Kidney function at 1 year after transplantation was significantly better in the BD group compared with the CD group. However, there was no significant difference between groups in kidney function at 3 and 5 years. Kidney function at 1 and 3 years after transplantation was significantly better in the SCD group than in the ECD group, although there was no difference between the groups in renal function at 5 years. There have been many reports stating that graft survival rate at 3e5 years after transplantation from ECDs is poor compared with SCDs. Aubert et al reported that compared with SCDs, the graft survival rate after 7 years from ECDs was lower (88% vs 80%; P < .001), and prognostic determinants of ECD transplants were donor-specific antiHLA antibodies and cold ischemia time [1]. Papachristou et al reported that patient survival after ECD is similar to that after SCD but graft survival is significantly lower. However, because the renal function of recipients from ECD is adequate for a long period, the grafts from ECDs could be used in older patients [2]. However, in our patients, no statistically significant difference between the ECD and SCD groups was found in kidney function after 5 years. Our study suggests the potential to achieve good performance even in ECD kidneys. We would like to continue research this topic in the future. CONCLUSION
In our patients, there was no significant difference between patient outcomes after receiving transplants from
KIHARA, NAKAMURA, YOKOYAMA ET AL
ECDs or SCDs. Therefore, the recipients’ quality of life was improved by receiving kidneys from ECDs. Owing to the low donor pool in Japan, we think that actively using ECD kidneys will increase the number of renal transplantations. REFERENCES [1] Aubert O, Kamar N, Vernerey D, Viglietti D, Martinez F, Duong-Van-Huyen JP, et al. Long term outcomes of transplantation using kidneys from expanded criteria donors: prospective, population based cohort study. BMJ 2015;351:h3557. [2] 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;46:3172e4. [3] Ferrer F, Mota A, Alves R, Bastos C, Macário F, Figueiredo A, et al. Renal transplantation with expanded criteria donors: the experience of one Portuguese center. Transplant Proc 2009;41:791e3. [4] Schnitzler MA, Whiting JF, Brennan DC, Lin G, Chapman W, Lowell J, et al. The expanded criteria donor dilemma in cadaveric renal transplantation. Transplantation 2003;75:1940e5. [5] Hassanain M, Tchervenkov J, Cantarovich M, Metrakos P, Paraskevas S, Keith D, et al. Delayed graft function has an equally bad impact on deceased donor renal graft survival in both standard criteria donors and expanded criteria donors. Transplant Proc 2009;41:133e4. [6] Domagala P, Kwiatkowski A, Wszola M, Czerwinski J, Cybula K, Trzebicki J, et al. Complications of transplantation of kidneys from expanded-criteria donors. Transplant Proc 2009;41: 2970e1. [7] Sellers MT, Velidedeoglu E, Bloom RD, Grossman RA, Markmann JW, Naji A, et al. Expanded-criteria donor kidneys: a single-center clinical and short-term financial analysisdcause for concern in retransplantation. Transplantation 2004;78:1670e5. [8] Ratner LE, Kraus E, Magnuson T, Bender JS. Transplantation of kidneys from expanded criteria donors. Surgery 1996;119:372e7. [9] Heuer M, Zeiger A, Kaiser GM, Mathé Z, Goldenberg A, Sauerland S, et al. Use of marginal organs in kidney transplantation for marginal recipients: too close to the margins of safety? Eur J Med Res 2010;15:31e4.