【进展】UNOS/OPTN 改进尸体供肾的分配制度Kidney Donor Profile Index (KDPI)
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UNOS and OPTN are considering a new allocation method for donor kidneys. Known as the Kidney Donor Profile Index (KDPI), kidney allocation would be based on survival-matching and age-matching with the recipient.
http://www.nejm.org/doi/full/10.1056/NEJMp1102728?query=featured_home
On February 16, 2011, the Organ Procurement and Transplantation Network (OPTN), the federal contractor responsible for overseeing solid-organ allocation in the United States, released for public comment three proposed concepts for the allocation of kidneys from deceased donors: using a Kidney Donor Profile Index (KDPI) to rank each kidney according to the length of time that it would be expected to function in an average transplant recipient, allocating the highest-quality 20% of kidneys to the 20% of candidates with the longest expected post-transplantation survival, and giving candidates within 15 years of the donor's age the highest priority in the allocation of the remaining 80% of kidneys.1 If these concepts were adopted, validated prediction models2,3 would be used to introduce into the kidney-allocation algorithm an element of matching of the estimated future survival of transplanted kidneys with that of recipients.
To place into context the importance of these concepts, it is necessary to understand the existing system. At its core, the current U.S. system for allocating kidneys from deceased donors focuses primarily on how long patients have been waiting for a transplant. This approach contrasts with the allocation algorithms for liver and heart transplantation, which allocate organs on the basis of medical urgency, and the lung-allocation system, which allocates organs on the basis of a mixture of medical urgency and expected survival for 1 year after transplantation.
Under the current system, approximately 15% of donated kidneys (those from older, or a subgroup of less healthy, donors) are designated as “expanded criteria donor” (ECD) kidneys and are allocated according to waiting time alone to transplant candidates who have consented to receive such an organ in anticipation of reducing their pretransplantation waiting time.4 The remaining kidneys are referred to as “standard criteria donor” (SCD) kidneys, and approximately 4% of them are allocated for simultaneous transplantation with a lifesaving organ (liver, heart, or lung), 9% are allocated to patients with zero HLA-A, -B, and -DR antigen mismatches with the donor organ, and the balance are allocated to candidates according to a point system. The point system awards one point for each year a patient is on the waiting list. For SCD kidneys, candidates are awarded one point for each HLA-DR antigen match with a donor organ and four points if they are sensitized against 80% or more of the deceased-donor pool. In addition, patients with kidney failure who have previously donated an organ are awarded priority on their local lists, and pediatric candidates are awarded preferential access to kidneys from deceased donors younger than 35 years of age. About half of all candidates are removed from the list, typically owing to death or worsening health status, without having undergone transplantation.
The United States is divided into 58 donor service areas (DSAs), each served by a single organ procurement organization (OPO) that is responsible for recovering deceased-donor organs for transplantation. Most DSAs have a population of 3 million to 10 million people. Waiting time varies considerably among DSAs according to the prevalence of end-stage kidney disease (which is generally higher in large urban populations); the efficiency of the OPO in identifying possible donors, obtaining consent for donation, and recovering organs from donors; the opportunities within the DSA for referral and wait-listing for transplantation; and the practices of the individual transplant centers regarding the acceptance and discard of organs. The typical time to transplantation among recipients ranges from less than 6 months to more than 72 months, depending on their DSA and blood type. Therefore, the value of the extra allocation priority (1 to 4 years) given for sensitization and HLA-DR matching varies by geographic location.
The current allocation algorithm does not (with the exception of ECD transplantation) account for differences in potential survival of recipients and donated organs, and the dichotomous ECD–SCD distinction does not accurately assess the relative survival potential of many deceased-donor kidneys.4,5 Moreover, the allocation priority awarded for longer waiting time, HLA-DR match, and sensitization does not reflect the biologic effects of these elements on the survival of candidates, allografts, or recipients. By focusing on waiting time, rather than appropriately weighted medical factors, the current system makes access to transplants very different for otherwise similar patients.
We strongly support the introduction of “survival matching” between donated kidneys and wait-listed kidney-transplant recipients. The current allocation system allows kidneys with very short potential post-transplantation survival to be distributed to candidates who are expected to survive for a long time after transplantation. This practice leads to a higher-than-necessary rate of repeat transplantation: candidates with long potential lifespans who receive kidneys with short expected survival have twice the rate of repeat transplantation of similar recipients who receive organs with longer expected survival. Conversely, the system allows kidneys with long expected post-transplantation survival to be distributed to candidates with only a limited potential for post-transplantation survival, leading to a high rate of allograft loss due to the death of the patient.
As a consequence of the current allocation system and the aging of the candidate pool, the lifespan of patients after kidney transplantation in the United States has declined by 18 months since 1995. Computer simulations based on the current donor pool suggest that more than 35,000 years of post-transplantation survival, and more than 10,000 years of incremental post-transplantation survival (i.e., extra years of life that would not have been achieved if the patient had continued to undergo dialysis rather than receiving a transplant), are lost each year.2 We believe that survival matching as described in the OPTN concept document has the potential to reclaim many of these lost years of life and therefore warrants serious consideration.
We also strongly support replacing the current ECD–SCD distinction with the KDPI.5 Based on characteristics collected at the time of organ recovery, the KDPI would rank the potential post-transplantation survival of each deceased-donor kidney in relation to that of all other recovered kidneys, so that, for example, a kidney with a KDPI of 0.3 would be recognized as having an expected survival potential lower than that of 29% and greater than that of 70% of recovered kidneys. The KDPI provides a far more granular and accurate characterization of a kidney's survival potential than the ECD–SCD dichotomy does and permits survival matching between donated kidneys and wait-listed transplant candidates. We suspect that utilization rates of shorter-lived kidneys will increase as accurate information about their survival potential becomes available and as the opportunity for potentially short-lived candidates to be allocated kidneys with long estimated post-transplantation survival is reduced.
The post-transplantation survival models have been validated (R2≥0.994) and are useful metrics for predicting lifetimes for use in kidney allocation.2,3 These models are highly successful in distinguishing patients with similar survival potential from those with very different survival potential and are in fact more accurate in their ability to predict long-term survival than those currently utilized in lung and liver allocation.3
The loss of tens of thousands of future life-years that might be realized and enjoyed by transplant recipients and the increase in the waiting list resulting from an unnecessarily high rate of repeat transplantation are intolerable consequences of the current kidney-transplant algorithm and urgently need correction through the mechanism of survival matching. Although we suspect that there are opportunities for improvements to the kidney-allocation concepts that have been submitted for public comment by the OPTN, we believe that the core concepts — adoption of the KDPI and survival matching — warrant the strongest endorsement and the earliest possible implementation by the kidney-transplant community.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
This article (10.1056/NEJMp1102728) was published on March 16, 2011, at NEJM.org.
Source Information
From the Department of Medicine, University of Michigan Medical School (A.B.L.), and the Arbor Research Collaborative for Health (K.P.M., R.A.W.) — both in Ann Arbor.
http://www.nejm.org/doi/full/10.1056/NEJMp1102728?query=featured_home
On February 16, 2011, the Organ Procurement and Transplantation Network (OPTN), the federal contractor responsible for overseeing solid-organ allocation in the United States, released for public comment three proposed concepts for the allocation of kidneys from deceased donors: using a Kidney Donor Profile Index (KDPI) to rank each kidney according to the length of time that it would be expected to function in an average transplant recipient, allocating the highest-quality 20% of kidneys to the 20% of candidates with the longest expected post-transplantation survival, and giving candidates within 15 years of the donor's age the highest priority in the allocation of the remaining 80% of kidneys.1 If these concepts were adopted, validated prediction models2,3 would be used to introduce into the kidney-allocation algorithm an element of matching of the estimated future survival of transplanted kidneys with that of recipients.
To place into context the importance of these concepts, it is necessary to understand the existing system. At its core, the current U.S. system for allocating kidneys from deceased donors focuses primarily on how long patients have been waiting for a transplant. This approach contrasts with the allocation algorithms for liver and heart transplantation, which allocate organs on the basis of medical urgency, and the lung-allocation system, which allocates organs on the basis of a mixture of medical urgency and expected survival for 1 year after transplantation.
Under the current system, approximately 15% of donated kidneys (those from older, or a subgroup of less healthy, donors) are designated as “expanded criteria donor” (ECD) kidneys and are allocated according to waiting time alone to transplant candidates who have consented to receive such an organ in anticipation of reducing their pretransplantation waiting time.4 The remaining kidneys are referred to as “standard criteria donor” (SCD) kidneys, and approximately 4% of them are allocated for simultaneous transplantation with a lifesaving organ (liver, heart, or lung), 9% are allocated to patients with zero HLA-A, -B, and -DR antigen mismatches with the donor organ, and the balance are allocated to candidates according to a point system. The point system awards one point for each year a patient is on the waiting list. For SCD kidneys, candidates are awarded one point for each HLA-DR antigen match with a donor organ and four points if they are sensitized against 80% or more of the deceased-donor pool. In addition, patients with kidney failure who have previously donated an organ are awarded priority on their local lists, and pediatric candidates are awarded preferential access to kidneys from deceased donors younger than 35 years of age. About half of all candidates are removed from the list, typically owing to death or worsening health status, without having undergone transplantation.
The United States is divided into 58 donor service areas (DSAs), each served by a single organ procurement organization (OPO) that is responsible for recovering deceased-donor organs for transplantation. Most DSAs have a population of 3 million to 10 million people. Waiting time varies considerably among DSAs according to the prevalence of end-stage kidney disease (which is generally higher in large urban populations); the efficiency of the OPO in identifying possible donors, obtaining consent for donation, and recovering organs from donors; the opportunities within the DSA for referral and wait-listing for transplantation; and the practices of the individual transplant centers regarding the acceptance and discard of organs. The typical time to transplantation among recipients ranges from less than 6 months to more than 72 months, depending on their DSA and blood type. Therefore, the value of the extra allocation priority (1 to 4 years) given for sensitization and HLA-DR matching varies by geographic location.
The current allocation algorithm does not (with the exception of ECD transplantation) account for differences in potential survival of recipients and donated organs, and the dichotomous ECD–SCD distinction does not accurately assess the relative survival potential of many deceased-donor kidneys.4,5 Moreover, the allocation priority awarded for longer waiting time, HLA-DR match, and sensitization does not reflect the biologic effects of these elements on the survival of candidates, allografts, or recipients. By focusing on waiting time, rather than appropriately weighted medical factors, the current system makes access to transplants very different for otherwise similar patients.
We strongly support the introduction of “survival matching” between donated kidneys and wait-listed kidney-transplant recipients. The current allocation system allows kidneys with very short potential post-transplantation survival to be distributed to candidates who are expected to survive for a long time after transplantation. This practice leads to a higher-than-necessary rate of repeat transplantation: candidates with long potential lifespans who receive kidneys with short expected survival have twice the rate of repeat transplantation of similar recipients who receive organs with longer expected survival. Conversely, the system allows kidneys with long expected post-transplantation survival to be distributed to candidates with only a limited potential for post-transplantation survival, leading to a high rate of allograft loss due to the death of the patient.
As a consequence of the current allocation system and the aging of the candidate pool, the lifespan of patients after kidney transplantation in the United States has declined by 18 months since 1995. Computer simulations based on the current donor pool suggest that more than 35,000 years of post-transplantation survival, and more than 10,000 years of incremental post-transplantation survival (i.e., extra years of life that would not have been achieved if the patient had continued to undergo dialysis rather than receiving a transplant), are lost each year.2 We believe that survival matching as described in the OPTN concept document has the potential to reclaim many of these lost years of life and therefore warrants serious consideration.
We also strongly support replacing the current ECD–SCD distinction with the KDPI.5 Based on characteristics collected at the time of organ recovery, the KDPI would rank the potential post-transplantation survival of each deceased-donor kidney in relation to that of all other recovered kidneys, so that, for example, a kidney with a KDPI of 0.3 would be recognized as having an expected survival potential lower than that of 29% and greater than that of 70% of recovered kidneys. The KDPI provides a far more granular and accurate characterization of a kidney's survival potential than the ECD–SCD dichotomy does and permits survival matching between donated kidneys and wait-listed transplant candidates. We suspect that utilization rates of shorter-lived kidneys will increase as accurate information about their survival potential becomes available and as the opportunity for potentially short-lived candidates to be allocated kidneys with long estimated post-transplantation survival is reduced.
The post-transplantation survival models have been validated (R2≥0.994) and are useful metrics for predicting lifetimes for use in kidney allocation.2,3 These models are highly successful in distinguishing patients with similar survival potential from those with very different survival potential and are in fact more accurate in their ability to predict long-term survival than those currently utilized in lung and liver allocation.3
The loss of tens of thousands of future life-years that might be realized and enjoyed by transplant recipients and the increase in the waiting list resulting from an unnecessarily high rate of repeat transplantation are intolerable consequences of the current kidney-transplant algorithm and urgently need correction through the mechanism of survival matching. Although we suspect that there are opportunities for improvements to the kidney-allocation concepts that have been submitted for public comment by the OPTN, we believe that the core concepts — adoption of the KDPI and survival matching — warrant the strongest endorsement and the earliest possible implementation by the kidney-transplant community.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
This article (10.1056/NEJMp1102728) was published on March 16, 2011, at NEJM.org.
Source Information
From the Department of Medicine, University of Michigan Medical School (A.B.L.), and the Arbor Research Collaborative for Health (K.P.M., R.A.W.) — both in Ann Arbor.
