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Survival of Kidney Allograft of Donors after Circulatory Death Is Similar to Donors after Brain Death: Experience in a Regional Program
Survival of Kidney Allograft of Donors after Circulatory Death Is Similar to Donors after Brain Death: Experience in a Regional Program M.A. Gentila, P. Castrob, L. Ballesterosa, M.C. Gracia-Guindoc, M. Cabellod, M.A. Mazuecose, A. Rodriguez-Benotf, C. Gonzalez-Corvilloa,*, J. Borregog, A.O. Ortegac, and M. Alonsob a Nephrology Department, Hospital Universitario Hospital U, Virgen del Rocío, Sevilla, Spain; bCoordinación Autonómica de Trasplantes, Andalucía, Spain; cNephrology Department, Hospital Universitario Virgen de las Nieves, Granada, Spain; dNephrology Department, Hospital Universitario Hospital U. Regional de Málaga, Spain; eNephrology Department, Hospital Universitario Puerta del Mar, Cádiz, Spain; fNephrology Department, Hospital Universitario Reina Sofía, Córdoba, Spain; and gNephrology Department, Hospital Universitario Ciudad de Jaén, Jaén, Spain
ABSTRACT Background. Donors after circulatory death (DCD) are an increasingly crucial source of organs to maintain deceased donor kidney transplant activity when faced with a standstill in donors after brain death (DBD). We analyzed the influence on graft survival since the use of DCD organs was implemented in Andalusia (2010e2014). Methods. We compared 164 kidney transplants from DCD (83 Maastricht type II and 81 type III) and 1488 DBD transplants in recipients over the age of 18, excluding combined transplants. Results. DCD were more frequently men from the A blood group who were younger (48.9 11 vs 55.2 15 years old for DBD, P < .001). Kidneys from DCD were implanted in younger recipients (51.2 11 vs 53.5 13 years old for DBD, P ¼ .03), more frequently in men from blood group A who spent less time in renal replacement therapy (39.8 vs 51.5 months), in a lower proportion of immunized recipients and re-transplant patients, and had worse HLA-DR compatibility. DCD presented a proportion of primary nonfunctional allografts and an initial need for dialysis of 8.8% and 69.6% vs 5.5% and 29.6% for DBD (P < .001). DCD allograft recipient survival was 96% and 96% at the first and third year respectively, vs 96% and 93% with a DBD graft (NS). Survival of the graft was 91% and 86% at the 1st and 3rd years, vs 90% and 86% with a DBD allograft (NS). No significant difference was found between Maastricht type II and III. DCD were related to lower graft survival versus DBD under the age of 50 (n ¼ 445), 86% vs 92% (P ¼ .02) in the third year, but were similar to DBD from age 50 to 59 (n ¼ 407) and higher than DBD over age 60 (n ¼ 636), 80% at the 3rd year (NS). The survival of DCD recipients was not different than DBD in those under 60 and was significantly better than DBD at or over the age of 60 (96% vs 87% in the 3rd year, P ¼ .036). In the multivariable survival study (Cox, covariates of influence previously demonstrated in our region) DCD are not a significant survival prognosis factor for the recipient or the allograft. Conclusions. With the current guidelines of donor selection and allocation of organs applied in Andalusia, the survival of kidney transplants from DCD overall is similar to DBD. The graft performance tends to be better than DBD over the age of 60, the main source of donors at present.
T
HE STANDSTILL in donations from DBD has encouraged the implementation of DCD in Andalusia from Maastricht type II and type III donors since 2010. We
*Address correspondence to Carmen Gonzalez-Corvillo, Hospital Universitario Virgen Del Rocio, Sevilla, Av/ Manuel Siurot Pc: 41013, Spain. E-mail: [email protected]
0041-1345/15 http://dx.doi.org/10.1016/j.transproceed.2015.09.045
ª 2015 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
2572
Transplantation Proceedings, 47, 2572e2574 (2015)
KIDNEY GRAFT SURVIVAL AFTER CIRCULATORY DEATH
2573
analyzed the results of survival rates [1] during the implementation time (2010e2014) based on information from our regional transplant register (SICATA, the transplant coordination service for the Andalusian public health system), updated on December 31, 2014. METHODS We compared recipient and allograft survival with DCD (N ¼ 164, 83 Maastricht type II and 81 type III) versus DBD (N ¼ 1488; recipients younger than 18 years old and combined transplants were excluded). We employed the Kaplan-Meier survival curve, compared by the log-rank test. The Cox test was used for the multivariable study using pretransplant factors previously demonstrated in our region as having a significant influence on prognosis (donor and recipient age, DM as cause of renal disease, time on renal replacement therapy, HCV positive serology, retransplant, HLA immunized, and HLA-DR incompatibility) as covariates [2].
RESULTS
Transplants from DCD were significantly different from DBD in diverse characteristics of donors and recipients (Table 1). DCD were more frequently men from the A blood group who were younger (48.9 11 vs 55.2 15 years old for DBD, P < .001). DCD kidneys were implanted in younger recipients (51.2 11 vs. 53.5 13 years old for DBD, P ¼ .03) more frequently in men from the A group, with less time spent on renal replacement therapy (39.8 vs 51.5 months, due to the different proportion of the A group), implanted in a lower proportion of immunized recipients and retransplants and with worse HLA-DR compatibility. Kidney Table 1. Donor and Recipient Characteristics
Donor Donor age (y) Donor 60 years old (%) Donor sex (% male) A group donor (%) Recipient Recipient age (y) Recipient 60 years old (%) Recipient sex (% male) A group recipient (%) Time on renal replacement therapy (mo) Cause of renal disease: diabetes (%) HCV-positive recipients Retransplant PRA 0e10% 10e50% >50% DR incompatibilities (%) 0 1 2
DCD
DBD
P
48.9 11 11.6 80.5 55.5
55.2 15 42.7 58.3 45.9
.000 .039 .000 .029
51.2 11 26.8 70.1 55.5 39.8 45
53.5 13 36.9 62.1 47.8 51.5 64
.027 .039 .043 .036 .022
7.9
9.9
NS (.4)
1.2 1.7
3.0 13.4
NS (.19) .009
92.7 7.3 0
75.1 15.6 6.8
.025
7.5 58.5 34.0
18.6 59.7 21.7
.038
transplants from DCD did not show different graft survival, death-censored recipient and graft, than kidney transplants from DBD (log-rank, P > .3) (Table 2). Transplants from DBD and DCD classified by type of DCD (Maastricht type II or type III) showed no differences regarding recipient or graft survival. DBD allografts from older donors (which were implanted in older recipients) showed, as expected, a significantly lower survival rate for the graft and the recipient than in other DBD age groups. DCD kidneys showed a significantly lower survival rate than those from DBD under 50 years old, 86% vs 92% at the third year (P ¼ .02), but survival was very similar to DBD from ages 50 to 59 and tended to be better than DBD over the age of 60, 80% in the 3rd year (P ¼ .18). The survival rate for recipients of DCD kidneys did not differ from DBD kidney recipients under the age of 60 and was significantly better than that of DBD kidney recipients over 60 years old (96% vs 87% at the 3rd year, P ¼ .036). According to the multivariable study, implanting DCD kidneys is not a significant survival prognosis factor in models that included the previously mentioned covariates. Odds ratios and 95% confidence intervals for the DCD factor are 1.07 (0.4e2.6, P ¼ .89) for recipient survival, 1.26 (0.8e2.1, P ¼ .37) for graft survival, and 1.34 (0.7e2.5, P ¼ .36) for death-censored graft survival. DCD are an increasingly important source of organs to maintain transplant programs. Without a doubt, ischemic damage from cardiac arrest or a prolonged agonizing phase frequently leads to initial functional renal failure and, potentially, to worsened allograft survival [3]. In the present analysis of a very limited number of patients, we verified a high incidence rate of functional delay with a need for dialysis, but over a short-term period recipient and graft survival were not significantly different from DBD. The performance of DCD was, predictably, worse than younger DBD (under the age of 50) but was very similar in median ages (50e59 years) and tended to be better than older DBD recipients. The interpretation of this analysis was difficult due to the different profiles of donors and recipients. It is obvious that during this phase of the implementation of a new procedure the teams have been cautious with donor selection (younger for DCD) and with recipients (less immunologic risk and shorter time on replacement therapy). Nevertheless, a multivariable study with corrections for main factors that affected the survival of the transplant continued to show no significant risk related to DCD. Therefore, with the selection criteria applied in our region Table 2. DCD and DBD Survival Survival
Recipient Allograft Death-Censored Allograft
Donor
1 year
2 years
3 years
DCD DBD DCD DBD DCD DBD
96 96 91 90 95 94
96 95 86 89 89 93
96 93 86 86 89 92
2574
during those years, DCD seems to be similar to DBD concerning survival. It is possible that as the number of cases increases, with additional criteria for procurement and the use of DCD, donation after circulatory death will prove to be a more or less important risk factor for survival. The influence of DCD over graft function, which at the same time represents a main predictive element for survival over a long-term period, has yet to be observed and analyzed. On the other hand, the results of analyzing this kind of donor should not be compared with the advantageous DBD, which is scarcer each day, but rather with the DBD that is predominant nowadays in our country: older donors with a cardiovascular cause of death. CONCLUSION
In a preliminary analysis of a limited number of patients with favorable characteristics, in our region DCD seems to
GENTIL, CASTRO, BALLESTEROS ET AL
offer similar survival to DBD. Thus, DCD may allow us to increase transplant activity without compromising the quality of results. An accurate evaluation of the impact over a medium to long period of time awaits a study of a larger number of expanded applications.
REFERENCES [1] Ming Y, Shao M, Tian T, She X, Liu H, Ye S, et al. Outcome of kidney transplantation between controlled cardiac death and brain death donors: a meta-analysis. Chin Med J 2014;127:2829e36. [2] Gentil MA, Pérez-Valdivia MA, Rodriguez-Benot A, Sola E, Osuna A, Mazuecos MA, et al. Renal transplant register of Andalusia, 2010 report: survival in relation to the factors used in recipient selection. Transplant Proc 2010;42:3130e3. [3] Nagaraja P, Roberts GW, Stephens M, Horvath S, Fialova J, Chavez R, et al. Influence of delayed graft function and acute rejection on outcomes after kidney transplantation from donors after cardiac death. Transplantation 2012;94:1218e23.
ABSTRACT Background. Donors after circulatory death (DCD) are an increasingly crucial source of organs to maintain deceased donor kidney transplant activity when faced with a standstill in donors after brain death (DBD). We analyzed the influence on graft survival since the use of DCD organs was implemented in Andalusia (2010e2014). Methods. We compared 164 kidney transplants from DCD (83 Maastricht type II and 81 type III) and 1488 DBD transplants in recipients over the age of 18, excluding combined transplants. Results. DCD were more frequently men from the A blood group who were younger (48.9 11 vs 55.2 15 years old for DBD, P < .001). Kidneys from DCD were implanted in younger recipients (51.2 11 vs 53.5 13 years old for DBD, P ¼ .03), more frequently in men from blood group A who spent less time in renal replacement therapy (39.8 vs 51.5 months), in a lower proportion of immunized recipients and re-transplant patients, and had worse HLA-DR compatibility. DCD presented a proportion of primary nonfunctional allografts and an initial need for dialysis of 8.8% and 69.6% vs 5.5% and 29.6% for DBD (P < .001). DCD allograft recipient survival was 96% and 96% at the first and third year respectively, vs 96% and 93% with a DBD graft (NS). Survival of the graft was 91% and 86% at the 1st and 3rd years, vs 90% and 86% with a DBD allograft (NS). No significant difference was found between Maastricht type II and III. DCD were related to lower graft survival versus DBD under the age of 50 (n ¼ 445), 86% vs 92% (P ¼ .02) in the third year, but were similar to DBD from age 50 to 59 (n ¼ 407) and higher than DBD over age 60 (n ¼ 636), 80% at the 3rd year (NS). The survival of DCD recipients was not different than DBD in those under 60 and was significantly better than DBD at or over the age of 60 (96% vs 87% in the 3rd year, P ¼ .036). In the multivariable survival study (Cox, covariates of influence previously demonstrated in our region) DCD are not a significant survival prognosis factor for the recipient or the allograft. Conclusions. With the current guidelines of donor selection and allocation of organs applied in Andalusia, the survival of kidney transplants from DCD overall is similar to DBD. The graft performance tends to be better than DBD over the age of 60, the main source of donors at present.
T
HE STANDSTILL in donations from DBD has encouraged the implementation of DCD in Andalusia from Maastricht type II and type III donors since 2010. We
*Address correspondence to Carmen Gonzalez-Corvillo, Hospital Universitario Virgen Del Rocio, Sevilla, Av/ Manuel Siurot Pc: 41013, Spain. E-mail: [email protected]
0041-1345/15 http://dx.doi.org/10.1016/j.transproceed.2015.09.045
ª 2015 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
2572
Transplantation Proceedings, 47, 2572e2574 (2015)
KIDNEY GRAFT SURVIVAL AFTER CIRCULATORY DEATH
2573
analyzed the results of survival rates [1] during the implementation time (2010e2014) based on information from our regional transplant register (SICATA, the transplant coordination service for the Andalusian public health system), updated on December 31, 2014. METHODS We compared recipient and allograft survival with DCD (N ¼ 164, 83 Maastricht type II and 81 type III) versus DBD (N ¼ 1488; recipients younger than 18 years old and combined transplants were excluded). We employed the Kaplan-Meier survival curve, compared by the log-rank test. The Cox test was used for the multivariable study using pretransplant factors previously demonstrated in our region as having a significant influence on prognosis (donor and recipient age, DM as cause of renal disease, time on renal replacement therapy, HCV positive serology, retransplant, HLA immunized, and HLA-DR incompatibility) as covariates [2].
RESULTS
Transplants from DCD were significantly different from DBD in diverse characteristics of donors and recipients (Table 1). DCD were more frequently men from the A blood group who were younger (48.9 11 vs 55.2 15 years old for DBD, P < .001). DCD kidneys were implanted in younger recipients (51.2 11 vs. 53.5 13 years old for DBD, P ¼ .03) more frequently in men from the A group, with less time spent on renal replacement therapy (39.8 vs 51.5 months, due to the different proportion of the A group), implanted in a lower proportion of immunized recipients and retransplants and with worse HLA-DR compatibility. Kidney Table 1. Donor and Recipient Characteristics
Donor Donor age (y) Donor 60 years old (%) Donor sex (% male) A group donor (%) Recipient Recipient age (y) Recipient 60 years old (%) Recipient sex (% male) A group recipient (%) Time on renal replacement therapy (mo) Cause of renal disease: diabetes (%) HCV-positive recipients Retransplant PRA 0e10% 10e50% >50% DR incompatibilities (%) 0 1 2
DCD
DBD
P
48.9 11 11.6 80.5 55.5
55.2 15 42.7 58.3 45.9
.000 .039 .000 .029
51.2 11 26.8 70.1 55.5 39.8 45
53.5 13 36.9 62.1 47.8 51.5 64
.027 .039 .043 .036 .022
7.9
9.9
NS (.4)
1.2 1.7
3.0 13.4
NS (.19) .009
92.7 7.3 0
75.1 15.6 6.8
.025
7.5 58.5 34.0
18.6 59.7 21.7
.038
transplants from DCD did not show different graft survival, death-censored recipient and graft, than kidney transplants from DBD (log-rank, P > .3) (Table 2). Transplants from DBD and DCD classified by type of DCD (Maastricht type II or type III) showed no differences regarding recipient or graft survival. DBD allografts from older donors (which were implanted in older recipients) showed, as expected, a significantly lower survival rate for the graft and the recipient than in other DBD age groups. DCD kidneys showed a significantly lower survival rate than those from DBD under 50 years old, 86% vs 92% at the third year (P ¼ .02), but survival was very similar to DBD from ages 50 to 59 and tended to be better than DBD over the age of 60, 80% in the 3rd year (P ¼ .18). The survival rate for recipients of DCD kidneys did not differ from DBD kidney recipients under the age of 60 and was significantly better than that of DBD kidney recipients over 60 years old (96% vs 87% at the 3rd year, P ¼ .036). According to the multivariable study, implanting DCD kidneys is not a significant survival prognosis factor in models that included the previously mentioned covariates. Odds ratios and 95% confidence intervals for the DCD factor are 1.07 (0.4e2.6, P ¼ .89) for recipient survival, 1.26 (0.8e2.1, P ¼ .37) for graft survival, and 1.34 (0.7e2.5, P ¼ .36) for death-censored graft survival. DCD are an increasingly important source of organs to maintain transplant programs. Without a doubt, ischemic damage from cardiac arrest or a prolonged agonizing phase frequently leads to initial functional renal failure and, potentially, to worsened allograft survival [3]. In the present analysis of a very limited number of patients, we verified a high incidence rate of functional delay with a need for dialysis, but over a short-term period recipient and graft survival were not significantly different from DBD. The performance of DCD was, predictably, worse than younger DBD (under the age of 50) but was very similar in median ages (50e59 years) and tended to be better than older DBD recipients. The interpretation of this analysis was difficult due to the different profiles of donors and recipients. It is obvious that during this phase of the implementation of a new procedure the teams have been cautious with donor selection (younger for DCD) and with recipients (less immunologic risk and shorter time on replacement therapy). Nevertheless, a multivariable study with corrections for main factors that affected the survival of the transplant continued to show no significant risk related to DCD. Therefore, with the selection criteria applied in our region Table 2. DCD and DBD Survival Survival
Recipient Allograft Death-Censored Allograft
Donor
1 year
2 years
3 years
DCD DBD DCD DBD DCD DBD
96 96 91 90 95 94
96 95 86 89 89 93
96 93 86 86 89 92
2574
during those years, DCD seems to be similar to DBD concerning survival. It is possible that as the number of cases increases, with additional criteria for procurement and the use of DCD, donation after circulatory death will prove to be a more or less important risk factor for survival. The influence of DCD over graft function, which at the same time represents a main predictive element for survival over a long-term period, has yet to be observed and analyzed. On the other hand, the results of analyzing this kind of donor should not be compared with the advantageous DBD, which is scarcer each day, but rather with the DBD that is predominant nowadays in our country: older donors with a cardiovascular cause of death. CONCLUSION
In a preliminary analysis of a limited number of patients with favorable characteristics, in our region DCD seems to
GENTIL, CASTRO, BALLESTEROS ET AL
offer similar survival to DBD. Thus, DCD may allow us to increase transplant activity without compromising the quality of results. An accurate evaluation of the impact over a medium to long period of time awaits a study of a larger number of expanded applications.
REFERENCES [1] Ming Y, Shao M, Tian T, She X, Liu H, Ye S, et al. Outcome of kidney transplantation between controlled cardiac death and brain death donors: a meta-analysis. Chin Med J 2014;127:2829e36. [2] Gentil MA, Pérez-Valdivia MA, Rodriguez-Benot A, Sola E, Osuna A, Mazuecos MA, et al. Renal transplant register of Andalusia, 2010 report: survival in relation to the factors used in recipient selection. Transplant Proc 2010;42:3130e3. [3] Nagaraja P, Roberts GW, Stephens M, Horvath S, Fialova J, Chavez R, et al. Influence of delayed graft function and acute rejection on outcomes after kidney transplantation from donors after cardiac death. Transplantation 2012;94:1218e23.