Global trends and challenges in deceased donor kidney allocation
2017; Elsevier BV; Volume: 91; Issue: 6 Linguagem: Inglês
10.1016/j.kint.2016.09.054
ISSN1523-1755
AutoresDiana A. Wu, Christopher J.E. Watson, J. Andrew Bradley, Rachel Johnson, John Forsythe, Gabriel C. Oniscu,
Tópico(s)Organ Transplantation Techniques and Outcomes
ResumoWorldwide, the number of patients able to benefit from kidney transplantation is greatly restricted by the severe shortage of deceased donor organs. Allocation of this scarce resource is increasingly challenging and complex. Striking an acceptable balance between efficient use of (utility) and fair access to (equity) the limited supply of donated kidneys raises controversial but important debates at ethical, medical, and social levels. There is no international consensus on the recipient and donor factors that should be considered in the kidney allocation process. There is a general trend toward a reduction in the influence of human leukocyte antigen mismatch and an increase in the importance of other factors shown to affect posttransplant outcomes, such as cold ischemia, duration of dialysis, donor and recipient age, and comorbidity. Increased consideration of equity has led to improved access to transplantation for disadvantaged patient groups. There has been an overall improvement in the transparency and accountability of allocation policies. Novel and contentious approaches in kidney allocation include the use of survival prediction scores as a criterion for accessing the waiting list and at the point of organ offering with matching of predicted graft and recipient survival. This review compares the diverse international approaches to deceased donor kidney allocation and their evolution over the last decade. Worldwide, the number of patients able to benefit from kidney transplantation is greatly restricted by the severe shortage of deceased donor organs. Allocation of this scarce resource is increasingly challenging and complex. Striking an acceptable balance between efficient use of (utility) and fair access to (equity) the limited supply of donated kidneys raises controversial but important debates at ethical, medical, and social levels. There is no international consensus on the recipient and donor factors that should be considered in the kidney allocation process. There is a general trend toward a reduction in the influence of human leukocyte antigen mismatch and an increase in the importance of other factors shown to affect posttransplant outcomes, such as cold ischemia, duration of dialysis, donor and recipient age, and comorbidity. Increased consideration of equity has led to improved access to transplantation for disadvantaged patient groups. There has been an overall improvement in the transparency and accountability of allocation policies. Novel and contentious approaches in kidney allocation include the use of survival prediction scores as a criterion for accessing the waiting list and at the point of organ offering with matching of predicted graft and recipient survival. This review compares the diverse international approaches to deceased donor kidney allocation and their evolution over the last decade. The superior outcomes of kidney transplantation over dialysis and the growing incidence of end-stage renal disease have led to an exponential increase in the need for kidney transplantation worldwide.1Tonelli M. Wiebe N. Knoll G. et al.Systematic review: kidney transplantation compared with dialysis in clinically relevant outcomes.Am J Transplant. 2011; 11: 2093-2109Crossref PubMed Scopus (757) Google Scholar In contrast, the number of deceased donors has changed little and is vastly insufficient.2Rudge C. Matesanz R. Delmonico F.L. Chapman J. International practices of organ donation.Br J Anaesth. 2012; 108: i48-i55Crossref PubMed Scopus (121) Google Scholar Consequently, patients face longer waiting times, as well as a higher risk for morbidity and mortality while on the waiting list. In the US alone, the number of patients on the waiting list has doubled over the past decade, reaching around 100,000 patients, median waiting time has increased to over 4.5 years, and nearly 5000 patients die while waiting for a deceased donor kidney transplant every year.3Matas A.J. Smith J.M. Skeans M.A. et al.OPTN/SRTR 2013 Annual Data Report: Kidney.Am J Transplant. 2015; 15: 1-34Crossref PubMed Scopus (334) Google Scholar Similar trends have been noted in other countries (Figure 1 and Table 1).Table 1Kidney transplant and waiting list figures 2003 versus 2013Data sources: UK,87NHS UK Transplant. Transplant Activity Report 2003-2004. Bristol, 2004. Available at: http://www.odt.nhs.uk/uk-transplant-registry/annual-activity-report/. Accessed August 1, 2016.Google Scholar, 88NHS Blood and Transplant. Organ Donation and Transplantation Activity Report 2013/14. Bristol, 2013. Available at: http://www.odt.nhs.uk/uk-transplant-registry/annual-activity-report/. 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Eurotransplant 2013 = Austria, Belgium, Croatia, Germany, Hungary, the Netherlands, Luxembourg, and Slovenia.ScandiatransplantbScandiatransplant: Denmark, Finland, Iceland, Norway, and Sweden.IsraelSpainFrance200320132003201320032013200320132003201320032013200320132003201320032013Population (million)cData from United Nations. Department of Economic and Social Affairs Population Division. World Population Prospects: The 2015 Revision. Total Population – Both Sexes. Available at: https://esa.un.org/unpd/wpp/Download/Standard/Population/. Accessed April 11, 2016.59.564.0291.0317.119.723.34.04.5118.8133.824.426.16.47.842.546.560.563.8Total kidney transplantsn1836325615138168955438821111153991458692611031262642051255221273074pmp30.950.95253.327.637.927.825.633.634.33842.319.733.848.354.935.248.2DD transplantsn13862142866811163325630675733453183654756551281991217019912673pmp23.333.529.835.216.52716.812.728.123.826.8298.616.446.846.732.941.9LD transplantsn450111464705732218252445864614032723477113660382136401pmp7.617.422.218.111.210.81112.95.410.511.113.311.117.41.48.22.26.3Patients on waiting list at year endn50745881dNote this number represents a downward trend since 2009.56514992531591105631843812382111201231133346976240264328538010736pmp85.391.9194.231380.845.379.597.3104.283.150.551.173.397.794.793.188.9168.3Died on waiting listn29827938954644453xx64659320741630xx113252pmp54.413.414.62.30.1xx5.44.40.82.82.53.8xx1.93.9Median waiting time, yr2.32.73.24.53.72.7xx3.33.71.11.2xxxx1.42.4DD, deceased donor; LD, living donor; pmp, per million population; x, data not available.a Eurotransplant 2003: Austria, Belgium, Germany, the Netherlands, Luxembourg and Slovenia. Eurotransplant 2013 = Austria, Belgium, Croatia, Germany, Hungary, the Netherlands, Luxembourg, and Slovenia.b Scandiatransplant: Denmark, Finland, Iceland, Norway, and Sweden.c Data from United Nations. Department of Economic and Social Affairs Population Division. World Population Prospects: The 2015 Revision. Total Population – Both Sexes. Available at: https://esa.un.org/unpd/wpp/Download/Standard/Population/. Accessed April 11, 2016.d Note this number represents a downward trend since 2009. Open table in a new tab DD, deceased donor; LD, living donor; pmp, per million population; x, data not available. While living donors usually donate to a specified recipient, in most countries, deceased organ donation is non-directed and organs are offered to patients on a waiting list via an allocation scheme. Allocation schemes are generally governed by appointed transplant organizations that may operate at a regional, national, or even international level. Ownership of deceased donor organs is a controversial matter; in some countries, they are considered a national resource, whereas in others, they are retained within the donor region, and sharing among regions may be limited to payback requirements. Thus, allocation schemes vary from simple local programs to complex national algorithms. Furthermore, there is no universal consensus on the factors that should be considered in the allocation process, leading to considerable variation in the way patients are prioritized within different schemes. The major debate in the allocation of scarce donor organs centers on the competing ethical values of utility (maximum outcomes) and equity (fairness). Consideration must be given to the efficient use of organs to optimize outcomes and the overall benefits to society, as well as to the welfare of individual patients and fair access to transplantation.4Gutmann T. Land W. The ethics of organ allocation: the state of debate.Transplant Rev. 1997; 11: 191-207Abstract Full Text PDF Scopus (27) Google Scholar Utility-based allocation prioritizes patients with the best chance of a favorable outcome, aiming to achieve the maximum benefit from every transplanted organ. Inevitably, this gives rise to a debate over how benefit should be measured, that is whether by graft survival, patient survival, life years gained from transplant, or quality of life. Furthermore, it disadvantages patients who are less likely to experience a good outcome, such as those who are older, have diabetes, have more comorbidity, or have been on dialysis for a longer period of time.5Meier-Kriesche H.-U. Port F.K. Ojo A.O. et al.Effect of waiting time on renal transplant outcome.Kidney Int. 2000; 58: 1311-1317Abstract Full Text Full Text PDF PubMed Scopus (515) Google Scholar, 6Meier-Kriesche H.U. Kaplan B. Waiting time on dialysis as the strongest modifiable risk factor for renal transplant outcomes: a paired donor kidney analysis.Transplantation. 2002; 74: 1377-1381Crossref PubMed Scopus (610) Google Scholar, 7Morris P.J. Johnson R.J. Fuggle S.V. et al.Analysis of factors that affect outcome of primary cadaveric renal transplantation in the UK. HLA Task Force of the Kidney Advisory Group of the United Kingdom Transplant Support Service Authority (UKTSSA).Lancet. 1999; 354: 1147-1152Abstract Full Text Full Text PDF PubMed Scopus (216) Google Scholar, 8Johnson R.J. Fuggle S.V. O'Neill J. et al.Factors influencing outcome after deceased heart beating donor kidney transplantation in the United Kingdom: an evidence base for a new national kidney allocation policy.Transplantation. 2010; 89: 379-386Crossref PubMed Scopus (51) Google Scholar, 9Wu C. Evans I. Joseph R. et al.Comorbid conditions in kidney transplantation: association with graft and patient survival.J Am Soc Nephrol. 2005; 16: 3437-3444Crossref PubMed Scopus (122) Google Scholar Although an increasing proportion of patients on the waiting list fall into the above categories, they still derive a significant survival benefit from transplantation.1Tonelli M. Wiebe N. Knoll G. et al.Systematic review: kidney transplantation compared with dialysis in clinically relevant outcomes.Am J Transplant. 2011; 11: 2093-2109Crossref PubMed Scopus (757) Google Scholar, 10Oniscu G.C. Brown H. Forsythe J.L. How great is the survival advantage of transplantation over dialysis in elderly patients?.Nephrol Dial Transplant. 2004; 19: 945-951Crossref PubMed Scopus (142) Google Scholar, 11Wolfe R.A. Ashby V.B. Milford E.L. et al.Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant.N Engl J Med. 1999; 341: 1725-1730Crossref PubMed Scopus (3953) Google Scholar, 12Rabbat C.G.T.K. Russell J.D. Churchill D.N. Comparison of mortality risk for dialysis patients and cadaveric first renal transplant recipients in Ontario, Canada.J Am Soc Nephrol. 2000; 11: 917-922Crossref PubMed Google Scholar The principle of equity necessitates fairness in organ allocation; however, this may be interpreted in various ways. Equity is commonly conceived as “equal opportunity,” that is, every person who may benefit from a transplant should have an equal opportunity of receiving one.13Courtney A.E. Maxwell A.P. The challenge of doing what is right in renal transplantation: balancing equity and utility.Nephron Clin Pract. 2008; 111: c62-c68Crossref PubMed Scopus (42) Google Scholar It is important not to misinterpret this as equality; although equality involves treating all patients exactly the same (i.e., allocation by lottery), it neglects the fact that patients do not start from equal circumstances.14Braveman P. Gruskin S. Defining equity in health.J Epidemiol Community Health. 2003; 57: 254-258Crossref PubMed Scopus (910) Google Scholar The discovery of human leukocyte antigen (HLA) matching as a major determinant of graft survival led to its principal role in the first formal allocation schemes.15Takemoto S. Terasaki P.I. Cecka J.M. et al.Survival of Nationally Shared, HLA-Matched Kidney Transplants from Cadaveric Donors.N Engl J Med. 1992; 327: 834-839Crossref PubMed Scopus (181) Google Scholar, 16Opelz G. The benefit of exchanging donor kidneys among transplant centers.N Engl J Med. 1988; 318: 1289-1292Crossref PubMed Scopus (71) Google Scholar, 17Gilks W.R. Bradley B.A. Gore S.M. Klouda P.T. Substantial benefits of tissue matching in renal transplantation.Transplantation. 1987; 43: 669-674Crossref PubMed Scopus (63) Google Scholar However, it became apparent that such schemes resulted in inequitable access to transplantation for difficult-to-match patients.18Gaston R.S. Ayres I. Dooley L.G. Diethelm A.G. Racial equity in renal transplantation. The disparate impact of HLA-based allocation.JAMA. 1993; 270: 1352-1356Crossref PubMed Scopus (129) Google Scholar, 19Rebellato L.M. Arnold A.N. Bozik K.M. Haisch C.E. HLA matching and the United Network for Organ Sharing Allocation System: impact of HLA matching on African-American recipients of cadaveric kidney transplants.Transplantation. 2002; 74: 1634-1636Crossref PubMed Scopus (22) Google Scholar, 20Rudge C. Johnson R.J. Fuggle S.V. Forsythe J.L. Renal transplantation in the United Kingdom for patients from ethnic minorities.Transplantation. 2007; 83: 1169-1173Crossref PubMed Scopus (53) Google Scholar Consequently, most schemes now award extra priority to highly sensitized patients and patients with rare HLA types (most commonly from ethnic minorities) who are biologically disadvantaged in finding a compatible donor, to equalize their opportunity for transplantation. “Queuing” (first come, first served) is another concept of equity that has been widely accepted in kidney allocation. However, with the increasing age and morbidity of patients on the waiting list, this approach has been challenged for favoring those who are able to survive the ever-increasing wait. Furthermore, with growing evidence for disparities in access to the waiting list, many schemes now measure the waiting time from the start date of dialysis as opposed to the listing date, although some countries are yet to adopt this approach. Priority for pediatric patients is universally acknowledged in view of the detrimental impact of renal failure and prolonged dialysis on growth and development (although the age cutoff and priority level substantially varies among different schemes). In contrast, the prioritization of younger adults over older ones is widely disputed. While advocates of the “fair innings” concept believe that equity should be measured by the opportunity to reach a normal life expectancy, critics argue that preferential allocation to younger patients is age discrimination.21Ladin K. Hanto D.W. Rational rationing or discrimination: balancing equity and efficiency considerations in kidney allocation.Am J Transplant. 2011; 11: 2317-2321Crossref PubMed Scopus (22) Google Scholar The “prudential lifespan” provides an alternative concept of equity through the allocation of kidneys by age matching. This justifies the allocation of younger (and therefore “higher quality” kidneys) to younger recipients and the allocation of older kidneys to older recipients because all patients are treated similarly at a particular stage of life.22Ross L.F. Parker W. Veatch R.M. et al.Equal Opportunity Supplemented by Fair Innings: equity and efficiency in allocating deceased donor kidneys.Am J Transplant. 2012; 12: 2115-2124Crossref PubMed Scopus (29) Google Scholar However, this approach becomes problematic if there is a discrepancy in the age distribution of donor and recipient pools. Moreover, age is just one of the many factors that influence the outcome of transplanted kidneys. A range of survival predictors are utilized in the emerging concept of longevity matching, where kidneys are allocated on the basis of matching estimated graft and recipient survival. This approach remains controversial, reflecting the enduring difficulties in achieving an acceptable balance between utility and equity. This review compares the allocation schemes of several different countries and explores their evolution over the last decade. The first UK national kidney allocation scheme was a simple HLA-matching scheme that was introduced in 1989.23Fuggle S.V. Johnson R.J. Rudge C.J. Forsythe J.L. Human leukocyte antigen and the allocation of kidneys from cadaver donors in the United Kingdom.Transplantation. 2004; 77: 618-620Crossref PubMed Scopus (22) Google Scholar One kidney from each donor was allocated nationally to a “beneficially mismatched recipient” (defined as HLA-A, -B, and -DR mismatch 000, 100, or 010), whereas the paired donor kidney was allocated locally according to individual center policies.17Gilks W.R. Bradley B.A. Gore S.M. Klouda P.T. Substantial benefits of tissue matching in renal transplantation.Transplantation. 1987; 43: 669-674Crossref PubMed Scopus (63) Google Scholar, 23Fuggle S.V. Johnson R.J. Rudge C.J. Forsythe J.L. Human leukocyte antigen and the allocation of kidneys from cadaver donors in the United Kingdom.Transplantation. 2004; 77: 618-620Crossref PubMed Scopus (22) Google Scholar A revised scheme was implemented in 1998, after 3 distinct tiers of HLA mismatch were identified as major influences on graft outcome.24Fuggle S.V. Johnson R.J. Bradley J.A. et al.Impact of the 1998 UK National Allocation Scheme for deceased heartbeating donor kidneys.Transplantation. 2010; 89: 372-378Crossref PubMed Scopus (15) Google Scholar Allocation was prioritized on a national basis for tier 1 (000 mismatch) followed by tier 2 (100, 010, and 110 mismatch) patients; allocation was on a local basis for tier 3 patients (all other HLA-mismatch grades). Within tiers 1 and 2, priority was given to pediatric patients ( 85%)534.719516.8Waiting time<1 yr49743.923620.31–3 yr39234.637031.93–5 yr14312.632628.15–7 yr484.215913.7≥7 yr534.7706.0Recipient age0–5 yr100.970.66–11 yr211.9171.512–17 yr524.6342.918–29 yr12210.81079.230–39 yr20017.717114.740–49 yr27324.127823.950–59 yr26623.526923.260–69 yr16314.420918≥70 yr262.3695.9Donor-recipient age difference 25 yr18516.313011.2Recipient blood groupO46741.251244.1A46040.642336.4B15013.216614.3AB564.9605.2HomozygosityHLA-A16114.214812.7HLA-B907.9847.2HLA-DR1039.114612.6HLA-A,B,DR161.4292.5Graft number195484.293980.9214913.218616.03242.1312.7460.550.4Diabetic746.5756.5Gender (male)69761.571761.8EthnicityWhite98186.682471.0Asian968.520517.7Black433.8958.2Other111.0312.7Not reported20.260.5ExchangeLocal center40235.518916.3Local area39935.260452.0Other33229.336831.7Median CIT18.5 h(IQR: 15.9–22.4)14.5 h(IQR: 11.4–17.9)1-year graft survival91.2%(95% CI: 89.3–92.7)94.1%(95% CI: 92.4–95.4)1-year patient survival95.5%(95% CI: 93.9–96.7)95.9%(95% CI: 94.2–97.1)CIT, cold ischemia time; cRF, calculated reaction frequency; DBD, donor after brain death; HLA, human leukocyte antigen; IQR, interquartile range; MM. mismatch. Open table in a new tab CIT, cold ischemia time; cRF, calculated reaction frequency; DBD, donor after brain death; HLA, human leukocyte antigen; IQR, interquartile range; MM. mismatch. The first US kidney allocation scheme was introduced in 1987, and a completely revised scheme was implemented for the first time in 2014.28Organ Procurement and Transplantation Network. Policy 8: Allocation of Kidneys. Virginia, 2014. Available at: https://optn.transplant.hrsa.gov/media/1200/optn_policies.pdf#nameddest=Policy_08. Accessed October 7, 2015.Google Scholar Under the former system, the country was divided into 58 donor service areas (DSAs), responsible for local procurement and allocation of deceased donor organs.29Organ Procurement and Transplantation Network. Kidney Allocation Policy 3.5. 2013. Available at: https://optn.transplant.hrsa.gov/media/1277/policynotice_20130701.pdf. Accessed October 7, 2015.Google Scholar Although there was mandatory national sharing of zero HLA-mismatched kidneys, these were required to be paid back to the procuring DSA. The large majority of organs were retained within and allocated by individual DSAs. Given that local organ supply relative to the demand varied widely among DSAs, substantial disparities were observed in the waiting time across the country.30Davis A.E. Mehrotra S. Ladner D.P. et al.Changes in geographic disparity in kidney transplantation since the final rule.Transplantation. 2014; 98: 931-936Cros
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