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Should Kidneys From Older Cadaveric Donors Be Age-Matched to the Recipient?
Should Kidneys From Older Cadaveric Donors Be Age-Matched to the Recipient? A. Foss, D. Tuvin, T. Leivestad, O. Øyen, and Ø. Bentdal
ABSTRACT Persistent shortage of kidneys for transplantation has forced most transplant centers to include procurement and use of kidneys from older donors. It is not clear whether the optimal use of these kidneys involve age-matching to the recipient. The aim of this study was to evaluate the clinical outcome of older cadaveric kidneys (⬎60 years), transplanted to young recipients (⬍50 years) and older recipients (⬎60 years). From 1989 through 2002, 252 first kidney grafts were procured from donors above the age of 60; 149 of the recipients to these grafts were above 60 years and 45 recipients were below 50. Minimum follow-up time was 12 months. Variables for waiting time to transplantation, DR mismatches, PRA, dialysis prior to transplantation, episodes of acute rejection, number of steroid-resistant rejections, creatinine levels, cold ischemia time, and causes of graft loss did not differ between the two groups. There was no significant difference in graft survival for young and older recipients receiving kidney from donors above 60 years of age. Graft survival at 1 year for young recipients was 90% and for older recipients 93% (NS). Five-year graft survival was 72% and 79%, respectively (NS). However, there was a significant positive effect on long-term graft survival if the donor kidney was less than 50 years. From our data, there is no evidence that age-matching of older donors has any beneficial effect on graft survival in kidney transplantation.
N
ORWAY HAS ONE transplant center, serving a population of 4.5 million people. At present, nearly 80 patients per million population per year enter renal replacement therapy, of whom 75%, according to the Norwegian Renal Registry, are considered potential candidates for transplantation. Based on our policy, living donors comprise 40% of the donor pool. Persistent shortage of kidneys for transplantation has forced us and most other transplant centers to broaden the criteria for donors accepted for kidney transplantation. This includes procurement of kidneys from older donors. It is widely acknowledged that the absolute mass of nephrons gradually decreases with age and that increasing age enlarges the probability of contemporary risk factors such as hypertension, diabetes mellitus, and atherosclerotic diseases. However, it is not completely clear whether the optimal use of kidneys from older donors should be agematched to the recipient.1–7 The aim of this study was to evaluate the clinical outcome of cadaveric donor kidneys above the age of 60 transplanted to young (⬍50) and old (⬎60) recipients.
PATIENTS AND METHODS From 1989 through 2002, 2364 first renal transplantations were performed at our center; 1336 grafts were procured from cadaveric donors, among which 252 grafts (19%) were from donors above the age of 60 years, mean age 67.3 (range 60.2 to 83.0; Table 1). Regarding the recipients, 149 were above 60 years of age (mean 68.9, range 60.0 to 80.1) and 45 were below 50 (mean 41.9, range 21.3 to 49.4). Variables for waiting time to transplantation, DR mismatches, PRA, dialysis prior to transplantation, episodes of acute rejection, number of steroid-resistant rejections, creatinine levels 3 months after transplantation, causes of graft loss, and cold ischemia time were measured. Graft survival rates were calculated using the Kaplan-Meier method. To evaluate the importance of age-matching on graft survival, the survival rates were censored for patient death with
From the Department of Surgery, Section of Transplant Surgery (A.F., D.T., O.Ø., Ø.B.) and Department of Immunology (T.L.), Rikshospitalet, Oslo, Norway. Address reprint requests to Aksel Foss, Department of Surgery, Section of Transplant Surgery, Rikshospitalet, N-0027 Oslo, Norway. E-mail: [email protected]
0041-1345/05/$–see front matter doi:10.1016/j.transproceed.2005.09.009
© 2005 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
3280
Transplantation Proceedings, 37, 3280 –3282 (2005)
AGE-MATCHING DONOR KIDNEYS AND RECIPIENTS
3281
Table 1. Donor and Recipient Characteristics
n Mean age, recipients Mean age, donors Waiting time for transplantation (mo) DR 0 mismatch (%) PRA ⫹ (%) Dialysis pretransplant S-creatinine (mol/L) Acute rejection episodes Steroid-resistant acute rejections Cold-ischemia time (h)
Recipients ⬎60 y
Recipients ⬍50 y
P
149 68.8 67.9 12 37 6 92 200.6 63.8% 16.8% 15.6
45 41.8 65.0 10 40 9 87 224.8 68.9% 26.7% 13.0
NS NS NS NS NS NS NS NS
functioning graft. Curves were compared using the Mantel-Haenzel test. Donors were routinely screened for malignancies, s-creatinine, renal disease, infections, and systemic pathologies. The immunosuppressive protocols have changed over the years, but were similar in the two study groups at any time point. From 1989 to 2000 it consisted of steroids, cyclosporine, and azathioprine. Between 2000 and 2001 steroids, cyclosporine, and basiliximab were used. Thereafter, mycophenolate mofetil was given as baseline immunosuppression in addition to steroids and cyclosporine. The minimum follow-up time was 12 months.
RESULTS
Waiting time to transplantation, variables for DR mismatches, PRA, dialysis prior to transplantation, creatinine levels, episodes of acute rejection during the first 3 months posttransplant, number of steroid-resistant rejections, and cold ischemia time were not significantly different between the two groups (Table 1). Causes of graft loss for recipients above 60 years were mainly patient death with functioning graft. For young recipients it was chronic allograft nephropathy. There was no significant difference in graft survival for recipients above 60 and recipients below 50 years of age (P ⫽ .33), receiving an old kidney above 60 years of age, compared by the Mantel-Haenzel test (Fig 1). Graft sur-
vival at 1 year for young recipients was 90% and for old recipients it was 93% (NS). At 5 years, graft survivals were 72% and 79%, respectively (NS), while the 5-year graft survivals of recipients receiving a kidney less than 50 years were 93% and 94% (data not shown).
DISCUSSION
Our data show no significant difference in graft survival for young and old recipients transplanted with a kidney donor above the age of 60. However, it is obvious that there has been an age-matched allocation of kidneys in our center, since 149 grafts out of the 252 old kidneys were transplanted to old recipients compared with only 45 to young recipients. If the recipients less than 50 years actually were transplanted with an old kidney of a better quality compared to old recipients (ie, donors with less comorbidity, such as hypertension, diabetes, and/or atherosclerotic disease), our data could be biased. However, when evaluating the donors retrospectively we do not find any such selection. The donors were primarily selected by DR mismatches, since we have previously demonstrated the importance of DR-matching in kidney transplantation,8 and secondly by waiting time and age. It has frequently been suggested that older kidneys have increased survival in older recipients as a result of the reduced physiological stress placed on the allograft by the older recipient.1,2,4 Our data do not confirm this, and do correspond with some other authors.5,7,8,9 Alexander et al found that the impact of both donor age and recipient age on the risk of graft failure were independent of one another up to 2 years after transplantation.5 Newstead and Dyer recommended that agematching should not be used as a recipient selection criterion7 and finally Kasiske and Snyder concluded that matching older kidneys with older patients did not improve allograft survival.9 Each transplant center should define a threshold for what is considered an old (or marginal) donor. This threshold should be set according to the level of graft survival aimed for and be related to the number of patients on the waiting list and the mean age of the donor pool.10 As shown, age-matching of older donors do not enhance graft survival. Consequently, there should be no medical argument for age-matching of these donors. However, an ethical dilemma exists since it is well documented that donor age has become the most important factor for long-term graft survival in kidney transplantation.11 Therefore, the overall graft survival of transplanted kidneys would probably increase by age-matching, since patient death with functioning graft would be reduced. The society should decide whether this is justified or not.
REFERENCES Fig 1. Graft survival (censored for patient death with a functioning graft). P ⫽ .33 (NS).
1. Swanson SJ, Hypolite IO, Agodoa LY, et al: Factors on early graft survival in adult cadaveric renal transplantation. Am J Transplant 2:68, 2002
3282 2. Waiser J, Schreiber M, Budde K, et al: Age-matching in renal transplantation. Nephrol Dial Transplant 2:696, 2000 3. Donnelly PK, Simpson AR, Milner AD, et al: Age-matching improves the results of renal transplantation with older donors. Nephrol Dial Transplant 5:808, 1990 4. Cecka JM, Terasaki PI: Optimal use for older donor kidneys: older recipients. Transplant Proc 27:801, 1995 5. Alexander JW, Bennet LE, Breen TJ: Effect of donor age on outcome of kidney transplantation. Transplantation 57:871, 1994 6. Roodnat JI, Zietse R, Mulder PG, Rischen-Vos J, et al: The vanishing importance of age in renal transplantation. Transplantation 67:576, 1999 7. Newstead CG, Dyer PA: The influence of increased age and
FOSS, TUVIN, LEIVESTAD ET AL age matching on graft survival after first cadaveric renal transplantation. Transplantation 54:441, 1992 8. Leivestad T, Albrechtsen D, Bratlie A, et al: The role of HLA compatibility in renal transplantation from living donors: an analysis of 379 grafts. Transplant Proc 22:153, 1990 9. Kasiske BL, Snyder J: Matching older kidneys with older patients does not improve allograft survival. J Am Soc Nephrol 13:1067, 2002 10. Persson NH, Persson MO, Ekberg H, et al: Renal transplantation from marginal donors: results and allocation stratatgies. Transplant Proc 33:3759, 2001 11. Terasaki PI, Cecka JM, Gjertson DW: Impact analysis: a method for evaluating the impact of factors in clinical renal transplantation. Clin Transplant 1998, p. 437
ABSTRACT Persistent shortage of kidneys for transplantation has forced most transplant centers to include procurement and use of kidneys from older donors. It is not clear whether the optimal use of these kidneys involve age-matching to the recipient. The aim of this study was to evaluate the clinical outcome of older cadaveric kidneys (⬎60 years), transplanted to young recipients (⬍50 years) and older recipients (⬎60 years). From 1989 through 2002, 252 first kidney grafts were procured from donors above the age of 60; 149 of the recipients to these grafts were above 60 years and 45 recipients were below 50. Minimum follow-up time was 12 months. Variables for waiting time to transplantation, DR mismatches, PRA, dialysis prior to transplantation, episodes of acute rejection, number of steroid-resistant rejections, creatinine levels, cold ischemia time, and causes of graft loss did not differ between the two groups. There was no significant difference in graft survival for young and older recipients receiving kidney from donors above 60 years of age. Graft survival at 1 year for young recipients was 90% and for older recipients 93% (NS). Five-year graft survival was 72% and 79%, respectively (NS). However, there was a significant positive effect on long-term graft survival if the donor kidney was less than 50 years. From our data, there is no evidence that age-matching of older donors has any beneficial effect on graft survival in kidney transplantation.
N
ORWAY HAS ONE transplant center, serving a population of 4.5 million people. At present, nearly 80 patients per million population per year enter renal replacement therapy, of whom 75%, according to the Norwegian Renal Registry, are considered potential candidates for transplantation. Based on our policy, living donors comprise 40% of the donor pool. Persistent shortage of kidneys for transplantation has forced us and most other transplant centers to broaden the criteria for donors accepted for kidney transplantation. This includes procurement of kidneys from older donors. It is widely acknowledged that the absolute mass of nephrons gradually decreases with age and that increasing age enlarges the probability of contemporary risk factors such as hypertension, diabetes mellitus, and atherosclerotic diseases. However, it is not completely clear whether the optimal use of kidneys from older donors should be agematched to the recipient.1–7 The aim of this study was to evaluate the clinical outcome of cadaveric donor kidneys above the age of 60 transplanted to young (⬍50) and old (⬎60) recipients.
PATIENTS AND METHODS From 1989 through 2002, 2364 first renal transplantations were performed at our center; 1336 grafts were procured from cadaveric donors, among which 252 grafts (19%) were from donors above the age of 60 years, mean age 67.3 (range 60.2 to 83.0; Table 1). Regarding the recipients, 149 were above 60 years of age (mean 68.9, range 60.0 to 80.1) and 45 were below 50 (mean 41.9, range 21.3 to 49.4). Variables for waiting time to transplantation, DR mismatches, PRA, dialysis prior to transplantation, episodes of acute rejection, number of steroid-resistant rejections, creatinine levels 3 months after transplantation, causes of graft loss, and cold ischemia time were measured. Graft survival rates were calculated using the Kaplan-Meier method. To evaluate the importance of age-matching on graft survival, the survival rates were censored for patient death with
From the Department of Surgery, Section of Transplant Surgery (A.F., D.T., O.Ø., Ø.B.) and Department of Immunology (T.L.), Rikshospitalet, Oslo, Norway. Address reprint requests to Aksel Foss, Department of Surgery, Section of Transplant Surgery, Rikshospitalet, N-0027 Oslo, Norway. E-mail: [email protected]
0041-1345/05/$–see front matter doi:10.1016/j.transproceed.2005.09.009
© 2005 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
3280
Transplantation Proceedings, 37, 3280 –3282 (2005)
AGE-MATCHING DONOR KIDNEYS AND RECIPIENTS
3281
Table 1. Donor and Recipient Characteristics
n Mean age, recipients Mean age, donors Waiting time for transplantation (mo) DR 0 mismatch (%) PRA ⫹ (%) Dialysis pretransplant S-creatinine (mol/L) Acute rejection episodes Steroid-resistant acute rejections Cold-ischemia time (h)
Recipients ⬎60 y
Recipients ⬍50 y
P
149 68.8 67.9 12 37 6 92 200.6 63.8% 16.8% 15.6
45 41.8 65.0 10 40 9 87 224.8 68.9% 26.7% 13.0
NS NS NS NS NS NS NS NS
functioning graft. Curves were compared using the Mantel-Haenzel test. Donors were routinely screened for malignancies, s-creatinine, renal disease, infections, and systemic pathologies. The immunosuppressive protocols have changed over the years, but were similar in the two study groups at any time point. From 1989 to 2000 it consisted of steroids, cyclosporine, and azathioprine. Between 2000 and 2001 steroids, cyclosporine, and basiliximab were used. Thereafter, mycophenolate mofetil was given as baseline immunosuppression in addition to steroids and cyclosporine. The minimum follow-up time was 12 months.
RESULTS
Waiting time to transplantation, variables for DR mismatches, PRA, dialysis prior to transplantation, creatinine levels, episodes of acute rejection during the first 3 months posttransplant, number of steroid-resistant rejections, and cold ischemia time were not significantly different between the two groups (Table 1). Causes of graft loss for recipients above 60 years were mainly patient death with functioning graft. For young recipients it was chronic allograft nephropathy. There was no significant difference in graft survival for recipients above 60 and recipients below 50 years of age (P ⫽ .33), receiving an old kidney above 60 years of age, compared by the Mantel-Haenzel test (Fig 1). Graft sur-
vival at 1 year for young recipients was 90% and for old recipients it was 93% (NS). At 5 years, graft survivals were 72% and 79%, respectively (NS), while the 5-year graft survivals of recipients receiving a kidney less than 50 years were 93% and 94% (data not shown).
DISCUSSION
Our data show no significant difference in graft survival for young and old recipients transplanted with a kidney donor above the age of 60. However, it is obvious that there has been an age-matched allocation of kidneys in our center, since 149 grafts out of the 252 old kidneys were transplanted to old recipients compared with only 45 to young recipients. If the recipients less than 50 years actually were transplanted with an old kidney of a better quality compared to old recipients (ie, donors with less comorbidity, such as hypertension, diabetes, and/or atherosclerotic disease), our data could be biased. However, when evaluating the donors retrospectively we do not find any such selection. The donors were primarily selected by DR mismatches, since we have previously demonstrated the importance of DR-matching in kidney transplantation,8 and secondly by waiting time and age. It has frequently been suggested that older kidneys have increased survival in older recipients as a result of the reduced physiological stress placed on the allograft by the older recipient.1,2,4 Our data do not confirm this, and do correspond with some other authors.5,7,8,9 Alexander et al found that the impact of both donor age and recipient age on the risk of graft failure were independent of one another up to 2 years after transplantation.5 Newstead and Dyer recommended that agematching should not be used as a recipient selection criterion7 and finally Kasiske and Snyder concluded that matching older kidneys with older patients did not improve allograft survival.9 Each transplant center should define a threshold for what is considered an old (or marginal) donor. This threshold should be set according to the level of graft survival aimed for and be related to the number of patients on the waiting list and the mean age of the donor pool.10 As shown, age-matching of older donors do not enhance graft survival. Consequently, there should be no medical argument for age-matching of these donors. However, an ethical dilemma exists since it is well documented that donor age has become the most important factor for long-term graft survival in kidney transplantation.11 Therefore, the overall graft survival of transplanted kidneys would probably increase by age-matching, since patient death with functioning graft would be reduced. The society should decide whether this is justified or not.
REFERENCES Fig 1. Graft survival (censored for patient death with a functioning graft). P ⫽ .33 (NS).
1. Swanson SJ, Hypolite IO, Agodoa LY, et al: Factors on early graft survival in adult cadaveric renal transplantation. Am J Transplant 2:68, 2002
3282 2. Waiser J, Schreiber M, Budde K, et al: Age-matching in renal transplantation. Nephrol Dial Transplant 2:696, 2000 3. Donnelly PK, Simpson AR, Milner AD, et al: Age-matching improves the results of renal transplantation with older donors. Nephrol Dial Transplant 5:808, 1990 4. Cecka JM, Terasaki PI: Optimal use for older donor kidneys: older recipients. Transplant Proc 27:801, 1995 5. Alexander JW, Bennet LE, Breen TJ: Effect of donor age on outcome of kidney transplantation. Transplantation 57:871, 1994 6. Roodnat JI, Zietse R, Mulder PG, Rischen-Vos J, et al: The vanishing importance of age in renal transplantation. Transplantation 67:576, 1999 7. Newstead CG, Dyer PA: The influence of increased age and
FOSS, TUVIN, LEIVESTAD ET AL age matching on graft survival after first cadaveric renal transplantation. Transplantation 54:441, 1992 8. Leivestad T, Albrechtsen D, Bratlie A, et al: The role of HLA compatibility in renal transplantation from living donors: an analysis of 379 grafts. Transplant Proc 22:153, 1990 9. Kasiske BL, Snyder J: Matching older kidneys with older patients does not improve allograft survival. J Am Soc Nephrol 13:1067, 2002 10. Persson NH, Persson MO, Ekberg H, et al: Renal transplantation from marginal donors: results and allocation stratatgies. Transplant Proc 33:3759, 2001 11. Terasaki PI, Cecka JM, Gjertson DW: Impact analysis: a method for evaluating the impact of factors in clinical renal transplantation. Clin Transplant 1998, p. 437