Long-Term Outcome of Renal Transplantation from Older Donors
http://www.100md.com
《新英格兰医药杂志》
To the Editor: We have used an approach similar to that of Remuzzi et al. (Jan. 26 issue)1 in the assessment of kidneys from donors older than 60 years of age and the implantation of organs with minimal renal changes as assessed on biopsy before transplantation. During a three-year period, we performed 150 renal biopsies (with a mean of 80 glomeruli obtained per biopsy) of kidneys from 75 cadaveric donors 61 through 84 years of age. A pathologist evaluated the biopsy specimens using strict, objective, blinded criteria (as discussed by Karpinski et al.2).
Kidneys of cadaveric donors in their 60s were adequate for single transplantation 44.1 percent of the time (total score, 0 to 3, according to the scoring system used by Karpinski et al.) and for dual transplantation 35.2 percent of the time (total score, 4 to 6). Kidneys from cadaveric donors 70 through 80 years of age were adequate for single and dual transplantation in 40.5 percent and 35.1 percent of cases, respectively. Our data confirm that preimplantation biopsy of kidneys from older cadaveric donors may be useful for increasing the number of kidneys available for transplantation.
Maria Rosaria Raspollini, M.D., Ph.D.
Luca Messerini, M.D.
Gian Luigi Taddei, M.D.
University of Florence
50134 Florence, Italy
mariarosaria.raspollini@unifi.it
References
Remuzzi G, Cravedi P, Perna A, et al. Long-term outcome of renal transplantion from older donors. N Engl J Med 2006;354:343-352.
Karpinski J, Lajoie G, Cattran D, et al. Outcome of kidney transplantation from high-risk donors is determined by both structure and function. Transplantation 1999;67:1162-1167.
To the Editor: The methods of Remuzzi et al. do not justify the conclusions the authors reached. A major limitation of their study is that the majority of the patients were recipients of dual allografts, whereas only eight patients received single allografts. An appropriate control group would have been recipients of dual kidneys from older donors without preimplantation biopsy. In the Cox regression model the authors used, preimplantation biopsy was included as an independent factor, but not whether the transplant was dual as compared with single. The appropriate conclusions seem to be that the rate of graft survival for dual allografts from older donors matches that for single allografts from donors 60 years old or younger and is better than that for single allografts from older donors. These conclusions are not new, since it has already been demonstrated that recipients of dual kidneys from donors selected with the use of expanded criteria for donation do as well as recipients of single kidneys from donors selected with standard criteria.1
Mandip Panesar, M.D.
Jayant Kumar, M.D.
Sameh Abul-Ezz, M.D.
University of Arkansas for Medical Sciences
Little Rock, AR 72205
References
Tan JC, Alfrey EJ, Dafoe DC, Millan MT, Scandling JD. Dual-kidney transplantation with organs from expanded criteria donors: a long-term follow-up. Transplantation 2004;78:692-696.
To the Editor: In the study by Remuzzi et al., graft survival for kidneys from older cadaveric donors that are allocated on the basis of histologic evaluation approached the rate for kidneys from younger donors. However, all methods of histologic evaluation of donor kidneys are not equivalent. Remuzzi et al. examined specimens obtained by core needle biopsy, as opposed to wedge biopsy, which is used in many centers with more variable results.1,2,3,4 Core biopsy samples the full cortical thickness, including arteries near the corticomedullary junction. In contrast, wedge-biopsy specimens often lack these vessels and frequently overrepresent the superficial cortex, with the greatest degree of glomerular and tubulointerstitial scarring in older people.
Remuzzi et al. report no graft losses resulting from biopsies performed with 16-gauge needles; they also report equivalent median cold-ischemia times for kidneys that were biopsied and those that were not biopsied. Thus, the use of histologic evaluation (if it is performed on core-biopsy specimens) in the assessment of kidneys from donors selected with the use of extended criteria should markedly reduce variability in the prediction of outcome.
Mark Haas, M.D., Ph.D.
Hamid Rabb, M.D.
Edward S. Kraus, M.D.
Johns Hopkins University School of Medicine
Baltimore, MD 21287
mhaas@jhmi.edu
References
Wang HJ, Kjellstrand CM, Cockfield SM, Solez K. On the influence of sample size on the prognostic accuracy and reproducibility of renal transplant biopsy. Nephrol Dial Transplant 1998;13:165-172.
Randhawa P. Role of donor kidney biopsies in renal transplantation. Transplantation 2001;71:1361-1365.
Ugarte R, Kraus E, Montgomery RA, et al. Excellent outcomes after transplantation of deceased donor kidneys with high terminal creatinine and mild pathologic lesions. Transplantation 2005;80:794-800.
Pokorna E, Vitko S, Chadimova M, Schuck O, Ekberg H. Proportion of glomerulosclerosis in procurement wedge renal biopsy cannot alone discriminate for acceptance of marginal donors. Transplantation 2000;69:36-43.
To the Editor: Remuzzi et al. suggest that a strategy based on histologic evaluation of kidneys from older donors improves outcome while expanding the donor pool. However, the data are inconclusive.
First, it appears that patients in the positive-reference group (who received single kidney transplants from donors 60 years of age or younger) were recruited from various transplantation centers without matching for retransplantation, panel-reactive antibodies, and immunosuppressive therapy. Moreover, the shorter waiting time of the patients in the study group, which is explained by their preferential position on the waiting list, might have biased the results.1
Second, there is no evidence supporting expansion of the donor pool. The numbers of discarded kidneys in the study and reference groups are not provided, and in their presentation of data, the authors do not take into account that more patients remain on dialysis if dual transplantation is performed. If such potential patients are included in the analysis, the proposed strategy results in more patients who remain on dialysis (Table 1). Such patients would be harmed, since the life expectancy of patients receiving dialysis is worse than that of graft recipients, even when the kidney comes from a donor selected with the use of expanded criteria for donation.2
Table 1. Effects of Histologic Evaluation of Donor Kidneys.
Luuk B. Hilbrands, M.D.
Jack F.M. Wetzels, M.D.
Radboud University Nijmegen Medical Center
6500 HB Nijmegen, the Netherlands
l.hilbrands@nier.umcn.nl
References
Meier-Kriesche HU, Kaplan B. Waiting time on dialysis as the strongest modifiable risk factor for renal transplant outcomes: a paired donor kidney analysis. Transplantation 2002;74:1377-1381.
Merion RM, Ashby VB, Wolfe RA, et al. Deceased-donor characteristics and the survival benefit of kidney transplantation. JAMA 2005;294:2726-2733.
The authors reply: We observed that a strategy based on histologic evaluation of kidneys from older donors improves outcome while expanding the donor pool. Hilbrands and Wetzels suggest that our data might be confounded by positive-reference recipients recruited from various centers. We addressed this concern with an additional analysis of the outcome of recipients of grafts from older donors that had undergone histologic evaluation and of age-matched and sex-matched recipients in the positive-reference group, with both groups of patients coming from two centers of the Double Kidney Group network. Graft survival in the two cohorts was similar.
The shorter waiting time in the study group is explained not by the preferential position on the waiting list but, rather, by the expansion of the donor pool, which enhanced the chance of retransplantation and was an additional advantage of our proposed strategy. Twenty-four percent of donors of kidneys that were biopsied were more than 74 years old. Kidneys from donors older than 74 years of age were never used for transplantation without preimplantation biopsy. Thus, our strategy actually translates into an expansion of the donor pool. This is a major advantage for patients on waiting lists, and this issue is not considered in the table provided by Hilbrands and Wetzels. They are correct in saying that more patients remain on dialysis if dual transplantations are performed. However, they do not mention that patients who return to dialysis after undergoing transplantation have a higher death rate than do patients receiving dialysis who have not undergone transplantation, a fact that should be considered in their calculations.1
Our mathematical modeling indicates that for 100 patients on a waiting list, at 10 years there will be 3 deaths among recipients of grafts that have undergone histologic evaluation and 11 deaths among recipients of grafts that have not undergone histologic evaluation (Figure 1). At the same time, the numbers of patients who are predicted to be alive with a functioning kidney are similar in the two groups (45 and 43, respectively).
Figure 1. Projected Deaths during a 10-Year Follow-up Period for 100 Patients on a Waiting List for Kidney Transplants.
Projections are made according to the use of kidneys from donors older than 60 years for single or dual transplantation on the basis of the histologic-evaluation score and for single transplantation without histologic evaluation. Data have been adjusted to include a projected 24 percent increase in the number of available donors (resulting from the use of biopsy-based histologic evaluation) and similar death rates among patients who receive a transplant, who remain on dialysis, or who return to dialysis after their transplant has failed. In the equation, x denotes time, y number, and Ln(x) the natural logarithm of time.
In the series by Tan and colleagues2 cited by Panesar et al., the two-year rate of graft survival (82.1 percent) was less than that in our series (94 percent), despite a younger mean age of donors (61±1 vs. 69±8, respectively). Other series of dual transplantations without histologic evaluation report even lower rates of survival.3 Moreover, the systematic use of kidneys from older donors for dual transplantation would unnecessarily reduce the number of transplantations. Raspollini et al. correctly report that some 40 percent of kidneys that are harvested from donors older than 60 years of age appear to be adequate for single transplantation on the basis of histologic evaluation. We agree with Haas et al. that core biopsy markedly reduces variability in the prediction of outcome for recipients of renal transplants.
Piero Ruggenenti, M.D.
Borislav D. Dimitrov, M.D.
Giuseppe Remuzzi, M.D.
Ospedali Riuniti di Bergamo
24128 Bergamo, Italy
manuelap@marionegri.it
References
Mortality rate comparisons of never, previously, and currently transplanted ESRD patients. Am J Kidney Dis 1992;20:Suppl 2:55-60.
Tan JC, Alfrey EJ, Dafoe DC, Millan MT, Scandling JD. Dual-kidney transplantation with organs from expanded criteria donors: a long-term follow-up. Transplantation 2004;78:692-696.
Bunnapradist S, Gritsch HA, Peng A, Jordan SC, Cho YW. Dual kidneys from marginal adult donors as a source for cadaveric renal transplantation in the United States. J Am Soc Nephrol 2003;14:1031-1036.
Kidneys of cadaveric donors in their 60s were adequate for single transplantation 44.1 percent of the time (total score, 0 to 3, according to the scoring system used by Karpinski et al.) and for dual transplantation 35.2 percent of the time (total score, 4 to 6). Kidneys from cadaveric donors 70 through 80 years of age were adequate for single and dual transplantation in 40.5 percent and 35.1 percent of cases, respectively. Our data confirm that preimplantation biopsy of kidneys from older cadaveric donors may be useful for increasing the number of kidneys available for transplantation.
Maria Rosaria Raspollini, M.D., Ph.D.
Luca Messerini, M.D.
Gian Luigi Taddei, M.D.
University of Florence
50134 Florence, Italy
mariarosaria.raspollini@unifi.it
References
Remuzzi G, Cravedi P, Perna A, et al. Long-term outcome of renal transplantion from older donors. N Engl J Med 2006;354:343-352.
Karpinski J, Lajoie G, Cattran D, et al. Outcome of kidney transplantation from high-risk donors is determined by both structure and function. Transplantation 1999;67:1162-1167.
To the Editor: The methods of Remuzzi et al. do not justify the conclusions the authors reached. A major limitation of their study is that the majority of the patients were recipients of dual allografts, whereas only eight patients received single allografts. An appropriate control group would have been recipients of dual kidneys from older donors without preimplantation biopsy. In the Cox regression model the authors used, preimplantation biopsy was included as an independent factor, but not whether the transplant was dual as compared with single. The appropriate conclusions seem to be that the rate of graft survival for dual allografts from older donors matches that for single allografts from donors 60 years old or younger and is better than that for single allografts from older donors. These conclusions are not new, since it has already been demonstrated that recipients of dual kidneys from donors selected with the use of expanded criteria for donation do as well as recipients of single kidneys from donors selected with standard criteria.1
Mandip Panesar, M.D.
Jayant Kumar, M.D.
Sameh Abul-Ezz, M.D.
University of Arkansas for Medical Sciences
Little Rock, AR 72205
References
Tan JC, Alfrey EJ, Dafoe DC, Millan MT, Scandling JD. Dual-kidney transplantation with organs from expanded criteria donors: a long-term follow-up. Transplantation 2004;78:692-696.
To the Editor: In the study by Remuzzi et al., graft survival for kidneys from older cadaveric donors that are allocated on the basis of histologic evaluation approached the rate for kidneys from younger donors. However, all methods of histologic evaluation of donor kidneys are not equivalent. Remuzzi et al. examined specimens obtained by core needle biopsy, as opposed to wedge biopsy, which is used in many centers with more variable results.1,2,3,4 Core biopsy samples the full cortical thickness, including arteries near the corticomedullary junction. In contrast, wedge-biopsy specimens often lack these vessels and frequently overrepresent the superficial cortex, with the greatest degree of glomerular and tubulointerstitial scarring in older people.
Remuzzi et al. report no graft losses resulting from biopsies performed with 16-gauge needles; they also report equivalent median cold-ischemia times for kidneys that were biopsied and those that were not biopsied. Thus, the use of histologic evaluation (if it is performed on core-biopsy specimens) in the assessment of kidneys from donors selected with the use of extended criteria should markedly reduce variability in the prediction of outcome.
Mark Haas, M.D., Ph.D.
Hamid Rabb, M.D.
Edward S. Kraus, M.D.
Johns Hopkins University School of Medicine
Baltimore, MD 21287
mhaas@jhmi.edu
References
Wang HJ, Kjellstrand CM, Cockfield SM, Solez K. On the influence of sample size on the prognostic accuracy and reproducibility of renal transplant biopsy. Nephrol Dial Transplant 1998;13:165-172.
Randhawa P. Role of donor kidney biopsies in renal transplantation. Transplantation 2001;71:1361-1365.
Ugarte R, Kraus E, Montgomery RA, et al. Excellent outcomes after transplantation of deceased donor kidneys with high terminal creatinine and mild pathologic lesions. Transplantation 2005;80:794-800.
Pokorna E, Vitko S, Chadimova M, Schuck O, Ekberg H. Proportion of glomerulosclerosis in procurement wedge renal biopsy cannot alone discriminate for acceptance of marginal donors. Transplantation 2000;69:36-43.
To the Editor: Remuzzi et al. suggest that a strategy based on histologic evaluation of kidneys from older donors improves outcome while expanding the donor pool. However, the data are inconclusive.
First, it appears that patients in the positive-reference group (who received single kidney transplants from donors 60 years of age or younger) were recruited from various transplantation centers without matching for retransplantation, panel-reactive antibodies, and immunosuppressive therapy. Moreover, the shorter waiting time of the patients in the study group, which is explained by their preferential position on the waiting list, might have biased the results.1
Second, there is no evidence supporting expansion of the donor pool. The numbers of discarded kidneys in the study and reference groups are not provided, and in their presentation of data, the authors do not take into account that more patients remain on dialysis if dual transplantation is performed. If such potential patients are included in the analysis, the proposed strategy results in more patients who remain on dialysis (Table 1). Such patients would be harmed, since the life expectancy of patients receiving dialysis is worse than that of graft recipients, even when the kidney comes from a donor selected with the use of expanded criteria for donation.2
Table 1. Effects of Histologic Evaluation of Donor Kidneys.
Luuk B. Hilbrands, M.D.
Jack F.M. Wetzels, M.D.
Radboud University Nijmegen Medical Center
6500 HB Nijmegen, the Netherlands
l.hilbrands@nier.umcn.nl
References
Meier-Kriesche HU, Kaplan B. Waiting time on dialysis as the strongest modifiable risk factor for renal transplant outcomes: a paired donor kidney analysis. Transplantation 2002;74:1377-1381.
Merion RM, Ashby VB, Wolfe RA, et al. Deceased-donor characteristics and the survival benefit of kidney transplantation. JAMA 2005;294:2726-2733.
The authors reply: We observed that a strategy based on histologic evaluation of kidneys from older donors improves outcome while expanding the donor pool. Hilbrands and Wetzels suggest that our data might be confounded by positive-reference recipients recruited from various centers. We addressed this concern with an additional analysis of the outcome of recipients of grafts from older donors that had undergone histologic evaluation and of age-matched and sex-matched recipients in the positive-reference group, with both groups of patients coming from two centers of the Double Kidney Group network. Graft survival in the two cohorts was similar.
The shorter waiting time in the study group is explained not by the preferential position on the waiting list but, rather, by the expansion of the donor pool, which enhanced the chance of retransplantation and was an additional advantage of our proposed strategy. Twenty-four percent of donors of kidneys that were biopsied were more than 74 years old. Kidneys from donors older than 74 years of age were never used for transplantation without preimplantation biopsy. Thus, our strategy actually translates into an expansion of the donor pool. This is a major advantage for patients on waiting lists, and this issue is not considered in the table provided by Hilbrands and Wetzels. They are correct in saying that more patients remain on dialysis if dual transplantations are performed. However, they do not mention that patients who return to dialysis after undergoing transplantation have a higher death rate than do patients receiving dialysis who have not undergone transplantation, a fact that should be considered in their calculations.1
Our mathematical modeling indicates that for 100 patients on a waiting list, at 10 years there will be 3 deaths among recipients of grafts that have undergone histologic evaluation and 11 deaths among recipients of grafts that have not undergone histologic evaluation (Figure 1). At the same time, the numbers of patients who are predicted to be alive with a functioning kidney are similar in the two groups (45 and 43, respectively).
Figure 1. Projected Deaths during a 10-Year Follow-up Period for 100 Patients on a Waiting List for Kidney Transplants.
Projections are made according to the use of kidneys from donors older than 60 years for single or dual transplantation on the basis of the histologic-evaluation score and for single transplantation without histologic evaluation. Data have been adjusted to include a projected 24 percent increase in the number of available donors (resulting from the use of biopsy-based histologic evaluation) and similar death rates among patients who receive a transplant, who remain on dialysis, or who return to dialysis after their transplant has failed. In the equation, x denotes time, y number, and Ln(x) the natural logarithm of time.
In the series by Tan and colleagues2 cited by Panesar et al., the two-year rate of graft survival (82.1 percent) was less than that in our series (94 percent), despite a younger mean age of donors (61±1 vs. 69±8, respectively). Other series of dual transplantations without histologic evaluation report even lower rates of survival.3 Moreover, the systematic use of kidneys from older donors for dual transplantation would unnecessarily reduce the number of transplantations. Raspollini et al. correctly report that some 40 percent of kidneys that are harvested from donors older than 60 years of age appear to be adequate for single transplantation on the basis of histologic evaluation. We agree with Haas et al. that core biopsy markedly reduces variability in the prediction of outcome for recipients of renal transplants.
Piero Ruggenenti, M.D.
Borislav D. Dimitrov, M.D.
Giuseppe Remuzzi, M.D.
Ospedali Riuniti di Bergamo
24128 Bergamo, Italy
manuelap@marionegri.it
References
Mortality rate comparisons of never, previously, and currently transplanted ESRD patients. Am J Kidney Dis 1992;20:Suppl 2:55-60.
Tan JC, Alfrey EJ, Dafoe DC, Millan MT, Scandling JD. Dual-kidney transplantation with organs from expanded criteria donors: a long-term follow-up. Transplantation 2004;78:692-696.
Bunnapradist S, Gritsch HA, Peng A, Jordan SC, Cho YW. Dual kidneys from marginal adult donors as a source for cadaveric renal transplantation in the United States. J Am Soc Nephrol 2003;14:1031-1036.