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Editorial the National Kidney Registry Editorial The National Kidney Registry Time to Buy In? Bushra Syed and Joshua J. Augustine CJASN 15: 168–170, 2020. doi: https://doi.org/10.2215/CJN.14581119 In this issue of CJASN, Leeser et al. (1) describe patient as measured by panel reactive antibody (PRA). Despite Department of and graft survival in patients who participated in the these risk factors, the National Kidney Registry recip- Nephrology and National Kidney Registry, a nonprofit, 501(c) organi- ients displayed superior death-censored graft survival. Hypertension, Cleveland Clinic, zation founded in 2007 to facilitate living kidney donor It is unclear what may have led to improved outcomes Cleveland, Ohio exchange. Outcomes of recipients of paired kidneys in in the National Kidney Registry recipients. Recipients n5 the National Kidney Registry ( 2363) were compared who participated in the National Kidney Registry may Correspondence: with outcomes in all living donor recipients from have been carefully selected with favorable resources, Dr. Joshua J. registry data (n554,497), control unrelated living do- education, and adherence. National Kidney Registry Augustine, nor recipients (n525,900), and control patients who recipients may also have had lower rates of donor- Department of fi Nephrology and received kidneys through non-National Kidney Regis- speci c antibodies or need for desensitization, although Hypertension, try paired donation (n54535). Because of shipping of such data were not available for the non-National Cleveland Clinic most kidneys, National Kidney Registry transplants had Kidney Registry cohort. Rates of desensitization in the Lerner College of a notably greater cold ischemic time (9 hours versus National Kidney Registry have dropped to ,5% since Medicine, 9500 1 hour for the primary control group). This correlated 2018 (3). This illustrates a strength of the program, Euclide Ave., Mailstop Q7, Cleveland, OH with a higher risk of delayed graft function in National allowing for matching of compatible donors despite 44195. Email: Kidney Registry recipients, with a 1.4 times risk (5% an over one fifth of recipients being highly sensitized [email protected] versus 3%; P,0.001) compared with other living donor with a PRA.80%. Recipients with a PRA $98% re- recipients.However,at amedianof3.7yearsoffollow-up mained disadvantaged as expected in the National for National Kidney Registry recipients, death-censored Kidney Registry (4). This risk can be mollified by graft survival and patient survival were similar com- matching with a paired donor with a lower titer cross- pared with control living donor recipients as a whole. match compared with the intended pair. In contrast to analysis of National Kidney Registry Original concepts of paired donation envisioned data, an Australian paired exchange cohort with a single hospitals and simultaneous transplants between median follow-up of 6.6 years demonstrated that cold paired donors (5). However, the success of national ischemic time was associated with outcomes in recip- exchange programs relies on the ability to separate ients of donors .50 years of age. Compared with transplants by geographic space and time, particularly cold ischemic time of 1–2 hours, cold ischemic time of when they involve longer transplant chains. One 4–8 hours was associated with an increased odds of concern with delaying subsequent transplants is that overall and death-censored graft failure with these chains may be broken, but a recent report from the older paired donors (hazard ratio, 1.93; 95% confidence National Kidney Registry found a low rate of broken interval, 1.21 to 3.09; P50.006 and hazard ratio, 1.91; chains of 5.8% (6). Primary reasons for chain breakage 95% confidence interval, 1.05 to 3.49; P50.04, respec- in that analysis included donor medical issues or tively (2). The follow-up in the current National Kidney donors backing out while serving as bridge donors Registry analysis is relatively short, and future studies (i.e., donors who donate at least 1 day after their with longer follow-up times are required to determine intended recipient has received a kidney). whether long-term survival is negatively affected by One trend has been a shift away from bridge donors, the greater cold ischemic time and delayed graft func- and to greater participation in an advanced donation tion in the National Kidney Registry cohort. program. Advanced donation occurs before transplan- One surprising finding is that National Kidney tation of the intended recipient, sometimes by months, Registry recipients appeared to have superior death- and before an alternative donor being selected for their censored allograft survival compared with recipients intended recipient. Preliminary data showed that of non-National Kidney Registry paired exchange advanced donation facilitated chains of transplants kidneys. Compared with this control group, National in National Kidney Registry, with approximately five Kidney Registry recipients were more likely to be black, transplants averaged for each advanced donation- with a higher percentage with prior transplantation, associated chain (7). One advantage of advanced greater dialysis vintage, greater cold ischemic time, and donation is that a prospective caregiver for the recipient a substantially higher rate of alloantibody sensitization may donate, recover from donor surgery, and later 168 Copyright © 2020 by the American Society of Nephrology www.cjasn.org Vol 15 February, 2020 CJASN 15: 168–170, February, 2020 National Kidney Paired Donation, Syed and Augustine 169 serve as a healthy support person for their intended re- key in preventing an accumulation of hard to match recipi- cipient. Additionally, a donor who has a specificwindowof ents in the National Kidney Registry (10). timefordonation,relatedtoworkortravel,maydonateatan The expectation from the National Kidney Registry is earlier convenient time. A risk related to advanced donation that centers participating will have an “all in” policy and is that the intended recipient may later encounter medical contribute all nondirected donors and incompatible paired issues leading to deactivation from the transplant list, and donors to the registry. Some transplant centers may prefer this risk is emphasized in the consent of donor–recipient internal swaps to maximize their own transplant numbers pairs for advanced donation in the National Kidney as well as avoiding costs and greater cold ischemic time Registry (7). associated with a national program. However, individual Other innovation has led to the success of national registry programs will still have difficulty in matching their most programs, and such innovation has been spearheaded by highly sensitized candidates, and may choose to enter such the National Kidney Registry (3). As above, at the expense of patients into a national registry. Such a registry will not longer cold ischemic time, shipping of kidneys has improved succeed if only the most difficult patients to match are convenience and willingness of living donors to participate entered. A key component of the success of the National without the need to travel to recipient centers, which may be Kidney Registry is to have large buy in from multiple thousands of miles away (8). The National Kidney Registry transplant programs, with the consistent addition of altru- utilizes global positioning system to track donor kidneys istic donors, particularly with blood group O, as well as during transport, allowing for monitoring of displaced compatible donor–recipient pairs. Compatible pairs who kidneys. The National Kidney Registry also implemented could otherwise proceed locally without exchange may be donor blood cryopreservation in 2015 allowing for cryo- particularly helpful in facilitating transplant chains in the preserved donor cells to be shipped to recipient centers. This National Kidney Registry, especially if the donor is O process improved the timeliness of crossmatches and elim- with a non-O recipient, or the recipient is AB with a non- inated the need for donors to provide repeat blood samples. AB donor (V. Chipman, B. Lee, M. Cooper, M.C. Cuffy, Donor computerized tomography scans are shared on the M. Ronin, G. Hil, S. Flechner, A. Thomas, D.A. Mandelbrot, National Kidney Registry website to avoid the need for A.D. Waterman, C.E. Freise, G.R. Roll, unpublished data). shipping of hard copies of films. Finally, a concept of Ideally there will be greater uni fication and national donation with “family vouchers” has been implemented participationinlargedonorexchangeprogramsinthe (9). This process allows for living donation in exchange for United States over time. If the early success of the National nontransferrable “vouchers” for a number of intended Kidney Registry is sustained, it may be the program of choice recipients (up to five immediate family members in the for national participation. The National Kidney Registry has National Kidney Registry, with cancellation of additional led the way in technology and innovation, and outcomes vouchers if one voucher is utilized). Such recipients do not demonstrate success for those classically disadvantaged for yet (and may never) need or qualify for transplantation, thus living donor transplant, including black recipients and blurring the lines between nondirected donation and donor those who are highly sensitized. The current report on exchange. Scenarios where the voucher program may be 10 years of transplantation through the registry is encourag- considered include older living donors with younger
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