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or elderly donors in renal transplantation: The outcome of grafts and patients
Cardiovascular Disease and/or Elderly Donors in Renal Transplantation: The Outcome of Grafts and Patients F. González-Martínez, L. Curi, S. Orihuela, G. González, N. Núñez, and M. Nin ABSTRACT Kidney transplant programs nowadays increasingly use elderly, hypertensive and cardiac disease donors (expanded criteria donors). The impact of these donors on patient and graft outcome was investigated in our transplant population. Among 257 consecutive cadaveric kidney transplants, 56 were from expanded criteria donors. The frequency of anuria, delayed graft function, and the days of renal failure were higher using organs from the expanded criteria donor group. Serum creatinine was higher in this group, although the statistical significance disappeared at 36 months. There were no significant differences in graft or patient survival during the first 3 years. The use of expanded criteria donors should not be discouraged, but recipient selection and immunosuppression use should be adapted and cold ischemia minimized.
D
UE TO the perennial shortage of transplantable organs, donor acceptability criteria are being relaxed cautiously to include marginal donors in an effort to expand the potential donor pool. The increased number of patients on the waiting list for kidney transplants has prompted medical teams to use donors who were previously rejected, namely elder by individuals or patients with cardiovascular disease (expanded donors). In spite of a normal serum creatinine, these kidneys may have a smaller glomerular mass and therefore a reduced functional reserve, which compromise outcomes.1 In the last few years we expanded our criteria to accept this kind of donor. The aim of this study was to compare the evolution of grafts and patients transplanted with kidneys from expanded criteria donors.
PATIENTS AND METHODS The analysis included 257 consecutive cadaveric kidney transplants performed in our institution between January 1997 and December 2002. The patients were subdivided into two groups: those whose grafts were from donors who were more than 50 years old and/or with cardiovascular disease donors (expanded group; n ⫽ 56) and those who were less than 51 years old and without cardiovascular disease donors (Control group, n ⫽ 201). Among the expanded donor group, 27 were elderly (more than 50 years old), 18 had cardiovascular disease (hypertension, cerebral hemorrhage, cerebral infarction, or coronary artery disease) and 11, both conditions. Female donors were more common in the expanded donor group (61% vs 24%, P ⬍ .001). There were no differences in the proportion of recipient genders, nor in age, cold ischemia time or HLA DR compatibility. The degree of HLA A-B compatibility was
higher in the expanded donor group (1.83 ⫾ 0.69 vs 1.54 ⫾ 0.83, P ⬍ .03). We analyzed the incidences of postoperative diuresis, delayed graft function (DGF), dialysis requirements, serum creatinines at months 1, 3, 6, 12, 18, 24, 30, and 36, and calculated graft and patient actuarial survivals. DGF was defined as the lack of a decrease in serum creatinine the day after the kidney transplant. Oliguria was considered to be a urinary output less than 400 mL/d. We calculated the average, standard deviations and percentage values of the groups. Comparisons were made using chi square, student’s t- and log-rank tests.
RESULTS
The frequency of expanded criteria donors was increased from 18% in 1998 to 2000 to 43% in 2001 to 2002 (P ⬍ .006). The frequency of anuria, DGF, and days of renal failure were higher in the expanded criteria donor cohort. Despite these finding, the days and number of dialysis treatments were similar (Table 1). Serum creatinine values were higher in the expanded donor group, but the statistical difference disappeared at month 36. At 1, 12, 24 and 36 months the serum creatinine was 2.9 ⫾ 1.9, 2.2 ⫾ 0.8, 2.2 ⫾ 0.7, and 2.1 ⫾ 0.7 mg% for the extended versus 2.0 ⫾ 1.4, 1.6 ⫾ 1.1, 1.7 ⫾ 0.8, and 1.8 ⫾ 0.8 mg% for the Control From the Instituto de Nefrologia y Urologia (F.G.-M., L.C., S.O., G.G., N.N., M.N.) and Centro de Nefrologia, Facultad de Medicina (F.G.-M., S.O., M.N.), Montevideo, Uruguay. Address reprint requests to F. González-Martı´nez, Solano Antuña 2990 Ap 601., Montevideo, Uruguay. E-mail: frgonzalez@ redfacil.com.uy
© 2004 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/04/$–see front matter doi:10.1016/j.transproceed.2004.07.033
Transplantation Proceedings, 36, 1687–1688 (2004)
1687
1688
GONZÁLEZ-MARTÍNEZ, CURI, ORIHUELA ET AL
Table 1. Frequency and Profile of Delayed Graft Function
Nonfunctioning grafts With anuria With delayed graft function Days of oliguria Days of renal failure Days on dialysis Numer of dialysis
Expanded Donors
Control
P
8.9 37 55 10.2 ⫾ 8.1 15.8 ⫾ 8.5 10.9 ⫾ 8.6 4.8 ⫾ 3.8
3.5 15 34 11.8 ⫾ 8.4 11.2 ⫾ 9.5 7.5 ⫾ 9.8 3.6 ⫾ 6.2
NS .004 .004 NS .04 NS NS
Abbreviation: NS, not significant.
group (P ⫽ .000, .01, .03, and NS, respectively). However, there were no significant differences in the graft or patient survival during the first 3 years: patient survivals at 12, 24, and 36 months were 99%, 99%, and 94% for the expanded group and 97%, 97%, and 97% for the Controls. The graft survivals for the same periods were 84%, 76%, and 71% for the expanded group and 91%, 90%, and 72% for the Control group. The length of first posttransplant hospitalization was higher in the expanded (24.5 ⫾ 15.0 days) versus the Control group (18.6 ⫾ 10.8 days; P ⬍ .001). While 55.6% of patients grafted with kidneys from donors with cardiovascular disease had DGF, only 29.6% of patients receiving organs from elderly donors had this complication (P ⬍ .07). The oliguria was also more frequent in the expanded criteria group (72.2%), including 44.41% from the elderly (P ⬍ .006). There were no statistical differences in mean serum creatinine values between both groups. DISCUSSION AND CONCLUSIONS
According to our results, the evolution of grafts from expanded donors was worse than that of grafts from conventional donors: oliguria and DGF function were more frequent. The evolution of renal function was also worse,
but at the end of the second year the difference was not significant. On the contrary, the actuarial kidney survival showed no statistical differences from those from conventional donors during the first 3 years. Therefore, our results show good graft survival despite more frequent DGF, results consistent with the literature.2,3 Ojo et al4 demonstrated a moderately negative impact of hypertensive donors on transplant outcome, concluding that these donors should not be used. We think these results are acceptable and that we must continue to expand the pool of donors using the expanded criteria donors to decrease the organ shortage. However, to improve graft outcomes, we must discuss recipient selection criteria for these organs, minimizing the ischemic/toxic aggressive factors in the donor,4 recipient, and preservation period. In the same way, we need to tailor immunosuppression regimes to avoid or decrease the doses of calcineurin inhibitors, expanding the use of induction with antilymphocyte antibodies. More studies are necessary to more accurately establish clinical, serum, and histologic markers of succesful outcomes. On the other hand, we need to emphasize renal protection from chronic damage to improve long-term results: low doses of steroids, optimized treatment of hypertension and hyperlipidemia, as well as minimized drug toxicity. REFERENCES 1. Alfrey EJ, Boissy AR, Lerner SM: Dual-kidney transplants: long-term results1. Transplantation 75:1232, 2003 2. Kumar A, Dasa SK, Srivastavaa A: Expanding the living related donor pool in renal transplantation: use of marginal donors. Transplant Proc 35:28, 2003 3. Michelon T, Piovesan F, Castilho C, et al: Marginal cadaveric kidney donors: an attractive way to expand the donor pool. Transplant Proc 34:2515, 2002 4. Ojo AO, Leichtman AB, Punch JD, et al: Survival in recipients of marginal cadaveric donor kidneys compared with other recipients and wait-listed transplant candidates. Am J Kidney Dis 36:589, 2000
D
UE TO the perennial shortage of transplantable organs, donor acceptability criteria are being relaxed cautiously to include marginal donors in an effort to expand the potential donor pool. The increased number of patients on the waiting list for kidney transplants has prompted medical teams to use donors who were previously rejected, namely elder by individuals or patients with cardiovascular disease (expanded donors). In spite of a normal serum creatinine, these kidneys may have a smaller glomerular mass and therefore a reduced functional reserve, which compromise outcomes.1 In the last few years we expanded our criteria to accept this kind of donor. The aim of this study was to compare the evolution of grafts and patients transplanted with kidneys from expanded criteria donors.
PATIENTS AND METHODS The analysis included 257 consecutive cadaveric kidney transplants performed in our institution between January 1997 and December 2002. The patients were subdivided into two groups: those whose grafts were from donors who were more than 50 years old and/or with cardiovascular disease donors (expanded group; n ⫽ 56) and those who were less than 51 years old and without cardiovascular disease donors (Control group, n ⫽ 201). Among the expanded donor group, 27 were elderly (more than 50 years old), 18 had cardiovascular disease (hypertension, cerebral hemorrhage, cerebral infarction, or coronary artery disease) and 11, both conditions. Female donors were more common in the expanded donor group (61% vs 24%, P ⬍ .001). There were no differences in the proportion of recipient genders, nor in age, cold ischemia time or HLA DR compatibility. The degree of HLA A-B compatibility was
higher in the expanded donor group (1.83 ⫾ 0.69 vs 1.54 ⫾ 0.83, P ⬍ .03). We analyzed the incidences of postoperative diuresis, delayed graft function (DGF), dialysis requirements, serum creatinines at months 1, 3, 6, 12, 18, 24, 30, and 36, and calculated graft and patient actuarial survivals. DGF was defined as the lack of a decrease in serum creatinine the day after the kidney transplant. Oliguria was considered to be a urinary output less than 400 mL/d. We calculated the average, standard deviations and percentage values of the groups. Comparisons were made using chi square, student’s t- and log-rank tests.
RESULTS
The frequency of expanded criteria donors was increased from 18% in 1998 to 2000 to 43% in 2001 to 2002 (P ⬍ .006). The frequency of anuria, DGF, and days of renal failure were higher in the expanded criteria donor cohort. Despite these finding, the days and number of dialysis treatments were similar (Table 1). Serum creatinine values were higher in the expanded donor group, but the statistical difference disappeared at month 36. At 1, 12, 24 and 36 months the serum creatinine was 2.9 ⫾ 1.9, 2.2 ⫾ 0.8, 2.2 ⫾ 0.7, and 2.1 ⫾ 0.7 mg% for the extended versus 2.0 ⫾ 1.4, 1.6 ⫾ 1.1, 1.7 ⫾ 0.8, and 1.8 ⫾ 0.8 mg% for the Control From the Instituto de Nefrologia y Urologia (F.G.-M., L.C., S.O., G.G., N.N., M.N.) and Centro de Nefrologia, Facultad de Medicina (F.G.-M., S.O., M.N.), Montevideo, Uruguay. Address reprint requests to F. González-Martı´nez, Solano Antuña 2990 Ap 601., Montevideo, Uruguay. E-mail: frgonzalez@ redfacil.com.uy
© 2004 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/04/$–see front matter doi:10.1016/j.transproceed.2004.07.033
Transplantation Proceedings, 36, 1687–1688 (2004)
1687
1688
GONZÁLEZ-MARTÍNEZ, CURI, ORIHUELA ET AL
Table 1. Frequency and Profile of Delayed Graft Function
Nonfunctioning grafts With anuria With delayed graft function Days of oliguria Days of renal failure Days on dialysis Numer of dialysis
Expanded Donors
Control
P
8.9 37 55 10.2 ⫾ 8.1 15.8 ⫾ 8.5 10.9 ⫾ 8.6 4.8 ⫾ 3.8
3.5 15 34 11.8 ⫾ 8.4 11.2 ⫾ 9.5 7.5 ⫾ 9.8 3.6 ⫾ 6.2
NS .004 .004 NS .04 NS NS
Abbreviation: NS, not significant.
group (P ⫽ .000, .01, .03, and NS, respectively). However, there were no significant differences in the graft or patient survival during the first 3 years: patient survivals at 12, 24, and 36 months were 99%, 99%, and 94% for the expanded group and 97%, 97%, and 97% for the Controls. The graft survivals for the same periods were 84%, 76%, and 71% for the expanded group and 91%, 90%, and 72% for the Control group. The length of first posttransplant hospitalization was higher in the expanded (24.5 ⫾ 15.0 days) versus the Control group (18.6 ⫾ 10.8 days; P ⬍ .001). While 55.6% of patients grafted with kidneys from donors with cardiovascular disease had DGF, only 29.6% of patients receiving organs from elderly donors had this complication (P ⬍ .07). The oliguria was also more frequent in the expanded criteria group (72.2%), including 44.41% from the elderly (P ⬍ .006). There were no statistical differences in mean serum creatinine values between both groups. DISCUSSION AND CONCLUSIONS
According to our results, the evolution of grafts from expanded donors was worse than that of grafts from conventional donors: oliguria and DGF function were more frequent. The evolution of renal function was also worse,
but at the end of the second year the difference was not significant. On the contrary, the actuarial kidney survival showed no statistical differences from those from conventional donors during the first 3 years. Therefore, our results show good graft survival despite more frequent DGF, results consistent with the literature.2,3 Ojo et al4 demonstrated a moderately negative impact of hypertensive donors on transplant outcome, concluding that these donors should not be used. We think these results are acceptable and that we must continue to expand the pool of donors using the expanded criteria donors to decrease the organ shortage. However, to improve graft outcomes, we must discuss recipient selection criteria for these organs, minimizing the ischemic/toxic aggressive factors in the donor,4 recipient, and preservation period. In the same way, we need to tailor immunosuppression regimes to avoid or decrease the doses of calcineurin inhibitors, expanding the use of induction with antilymphocyte antibodies. More studies are necessary to more accurately establish clinical, serum, and histologic markers of succesful outcomes. On the other hand, we need to emphasize renal protection from chronic damage to improve long-term results: low doses of steroids, optimized treatment of hypertension and hyperlipidemia, as well as minimized drug toxicity. REFERENCES 1. Alfrey EJ, Boissy AR, Lerner SM: Dual-kidney transplants: long-term results1. Transplantation 75:1232, 2003 2. Kumar A, Dasa SK, Srivastavaa A: Expanding the living related donor pool in renal transplantation: use of marginal donors. Transplant Proc 35:28, 2003 3. Michelon T, Piovesan F, Castilho C, et al: Marginal cadaveric kidney donors: an attractive way to expand the donor pool. Transplant Proc 34:2515, 2002 4. Ojo AO, Leichtman AB, Punch JD, et al: Survival in recipients of marginal cadaveric donor kidneys compared with other recipients and wait-listed transplant candidates. Am J Kidney Dis 36:589, 2000