New Insights Into the Alleged Kidney Donor Profile Index Labeling Effect on Kidney Utilization

The Kidney Donor Profile Index (KDPI) became a driving factor in deceased donor kidney allocation on December 4, 2014, with the implementation of the kidney allocation system (KAS). On April 20, 2016, the annual recalibration of the Kidney Donor Risk Index into KDPI was incorrectly programmed in DonorNet, resulting in erroneously high KDPI values, by between 1 and 21 percentage points (e.g. actual KDPI of 70% was displayed as 86%). The error was corrected on May 19, 2016, <24 h after being recognized. During this 30‐day period, the distribution of recipients largely resembled pre‐KAS patterns. The observed discard rate of 22.9% was higher than the post‐KAS average of 19.6% (odds ratio [OR]: 1.22) but far lower than the projected rate of 31.4% (OR: 1.96) based on the usual discard rate by KDPI relationship, suggesting clinicians and patients did not rely heavily on this single number (KDPI) in kidney‐utilization decisions. Still, risk‐adjusted analyses suggest the elevated discard rate was most likely attributable to the erroneously high KDPIs, not a shift in donor characteristics or random chance. The rise in discard rate was sharply higher for kidneys with inflated KDPI that crossed the 85% policy threshold (OR: 1.46; p = 0.049) versus those that did not (OR: 1.06; p = 0.631).     

First Report on the OPTN National Variance: Allocation of A2/A2B Deceased Donor Kidneys to Blood Group B Increases Minority Transplantation

In 2002, the Organ Procurement and Transplantation Network (OPTN) Minority Affairs Committee (MAC) implemented a national, prospective, “variance of practice” to allow deceased donor, ABO blood group incompatible, A₂ antigen, kidney transplantation into blood group B recipients; outcomes of this cohort were compared to ABO compatible recipients. The goal of the variance was to increase the number of transplants to B candidates without negatively impacting survival or compromising system equity. Only B recipients with low anti‐A IgG titers (<1:8) were eligible to receive these kidneys. Across eight participating Donation Service Areas (DSA), there were 101 A₂/A₂B to B transplants through 12/31/11, of which the majority of the recipients (61%) were ethnic minorities. At 12, 24, and 36 months, Kaplan–Meier graft survival rates for the B recipients of A₂/A₂B kidneys were 95.0%, 90.6%, and 85.4%, respectively, comparable to outcomes for B recipients of B kidneys, 92.6%, 87.9%, and 82.5%, respectively (p‐value = 0.48). Five DSAs increased the proportion of B transplants during 41 months postvariance, with a lesser proportional decrease in blood group A transplants. The data support the proposition that this allocation algorithm may provide a robust mechanism to increase access of blood group B minority candidates to kidney transplantation.     

Unintended Consequences of the New National Kidney Allocation Policy in the United States

The new national Kidney Allocation System of the Organ Procurement and Transplantation Network (OPTN), effective as of December 4, 2014, was designed to improve the chances of transplanting the most highly sensitized patients on the waitlist, those with calculated panel reactive antibody values of 98%, 99% and 100%. Recently, it was suggested that these highly sensitized patients will experience inequitable access, given the reported high prevalence of antibodies to HLA‐DP, and the fact that only about 1/3 of deceased donors are typed for HLA‐DP antigens. Here we report that 320/2948 flow cytometric crossmatches performed for the Northwestern transplant program over the past 28 months were positive solely due to HLA‐DP donor‐specific antibodies (11%; 16.5% of patients with HLA antibodies—sensitized patients). We further show that 58/207 (12%) HLA‐DR serologically matched donor‐recipient pairs had a positive B cell flow crossmatch due to donor‐specific HLA class II antibodies, and 2/34 (6%) serologic zero‐HLA‐A‐B‐DR mismatch had a positive flow crossmatch due to HLA‐DSA. We therefore provide information regarding the necessity and importance of complete donor HLA typing including both chains of the HLA‐DP antigen (encoded by HLA‐DPA1 and HLA‐DPB1) at the time of organ offer.     

Greater complexity and monitoring of the new Kidney Allocation System: Implications and unintended consequences of concentric circle kidney allocation on network complexity

The deceased donor kidney allocation system in the United States has undergone several rounds of iterative changes, but these changes were not explicitly designed to address the geographic variation in access to transplantation. The new allocation system, expected to start in December 2020, changes the definition of “local allocation” from the Donation Service Area to 250 nautical mile circles originating from the donor hospital. While other solid organs have adopted a similar approach, the larger number of both kidney transplant centers and transplant candidates is likely to have different consequences. Here, we discuss the incredible increase in complexity in allocation, discuss some of the likely intended and unintended consequences, and propose metrics to monitor the new system.     

Kidney Transplantation From a Donor With Sickle Cell Disease

In the United States, >100 000 patients are waiting for a kidney transplant. Given the paucity of organs available for transplant, expansion of eligibility criteria for deceased donation is of substantial interest. Sickle cell disease (SCD) is viewed as a contraindication to kidney donation, perhaps because SCD substantially alters renal structure and function and thus has the potential to adversely affect multiple physiological processes of the kidney. To our knowledge, transplantation from a donor with SCD has never been described in the literature. In this paper, we report the successful transplantation of two kidneys from a 37‐year‐old woman with SCD who died from an intracranial hemorrhage. Nearly 4 mo after transplant, both recipients are doing well and are off dialysis. The extent to which kidneys from donors with SCD can be safely transplanted with acceptable outcomes is unknown; however, this report should provide support for the careful expansion of kidneys from donors with SCD without evidence of renal dysfunction and with normal tissue architecture on preimplantation biopsies.     

A Share 21 model in liver transplantation: Impact on waitlist outcomes

With the introduction of Model for End‐Stage Liver Disease‐Sodium (MELD‐Na)–based allocation, the score at which patients benefit from liver transplantation (LT) has shifted from a score of 15 to 21. This study aimed to evaluate waitlist outcomes in patients with MELD‐Na scores <21 and explore the utility of replacing “Share 15” with “Share 21.” The study uses data from the Organ Procurement and Transplantation Network/United Network for Organ Sharing registry. All adult patients registered for LT after implementation of the MELD‐Na–based allocation were evaluated. Waitlist patients with initial and final scores <21 were eligible. Patients with exception scores were excluded. To explore the potential impact of a Share 21 model, patients with an initial MELD‐Na score of 6‐14 (Group 1) and those with a score of 15‐20 (Group 2) were compared for waitlist outcomes. There were 3686 patients with an initial score of 6‐14 (Group 1) and 3282 with a score of 15‐20 (Group 2). Group 2, when compared to Group 1, showed comparable risk of mortality (adjusted hazard ratio [aHR] 1.00, P = .97), higher transplant probability (aHR 3.25, P < .001), and lower likelihood of removal from listing because of improvement (aHR 0.74, P = .011). Share 21 may enhance transplant opportunities and increase parity for patients with higher MELD‐Na scores without compromising waitlist outcomes.     

A2/A2B to B Renal Transplantation: Past,Present, and Future Directions

One component of the new national kidney allocation system (KAS) in the United States that was implemented on December 4, 2014, was the allocation of kidneys from A₂ and A₂B (A, non‐A₁ and AB, non‐A₁B) deceased donors into blood group B candidates (A₂/A₂B → B). In so far as this is an important component of the new KAS that has the potential to further increase the access to transplantation for blood group B candidates on the waiting list, most of whom are minority candidates, we will review the body of evidence and historical perspectives that led to its inclusion in the new KAS. This review will also describe prospects for more widespread use of A₂/A₂B → B transplantation and a novel mechanism of humoral immunosuppression in B patients before and after transplantation with an A₂ or A₂B kidney.     

Kidney Exchange to Overcome Financial Barriers to Kidney Transplantation

Organ shortage is the major limitation to kidney transplantation in the developed world. Conversely, millions of patients in the developing world with end‐stage renal disease die because they cannot afford renal replacement therapy—even when willing living kidney donors exist. This juxtaposition between countries with funds but no available kidneys and those with available kidneys but no funds prompts us to propose an exchange program using each nation's unique assets. Our proposal leverages the cost savings achieved through earlier transplantation over dialysis to fund the cost of kidney exchange between developed‐world patient–donor pairs with immunological barriers and developing‐world patient–donor pairs with financial barriers. By making developed‐world health care available to impoverished patients in the developing world, we replace unethical transplant tourism with global kidney exchange—a modality equally benefitting rich and poor. We report the 1‐year experience of an initial Filipino pair, whose recipient was transplanted in the United states with an American donor's kidney at no cost to him. The Filipino donor donated to an American in the United States through a kidney exchange chain. Follow‐up care and medications in the Philippines were supported by funds from the United States. We show that the logistical obstacles in this approach, although considerable, are surmountable.     

Measuring and monitoring equity in access to deceased donor kidney transplantation

The Organ Procurement and Transplantation Network monitors progress toward strategic goals such as increasing the number of transplants and improving waitlisted patient, living donor, and transplant recipient outcomes. However, a methodology for assessing system performance in providing equity in access to transplants was lacking. We present a novel approach for quantifying the degree of disparity in access to deceased donor kidney transplants among waitlisted patients and determine which factors are most associated with disparities. A Poisson rate regression model was built for each of 29 quarterly, period‐prevalent cohorts (January 1, 2010‐March 31, 2017; 5 years pre–kidney allocation system [KAS], 2 years post‐KAS) of active kidney waiting list registrations. Inequity was quantified as the outlier‐robust standard deviation (SD_w) of predicted transplant rates (log scale) among registrations, after “discounting” for intentional, policy‐induced disparities (eg, pediatric priority) by holding such factors constant. The overall SD_w declined by 40% after KAS implementation, suggesting substantially increased equity. Risk‐adjusted, factor‐specific disparities were measured with the SD_w after holding all other factors constant. Disparities associated with calculated panel‐reactive antibodies decreased sharply. Donor service area was the factor most associated with access disparities post‐KAS. This methodology will help the transplant community evaluate tradeoffs between equity and utility‐centric goals when considering new policies and help monitor equity in access as policies change.     

Geographic disparity in kidney transplantation under KAS

The Kidney Allocation System fundamentally altered kidney allocation, causing a substantial increase in regional and national sharing that we hypothesized might impact geographic disparities. We measured geographic disparity in deceased donor kidney transplant (DDKT) rate under KAS (6/1/2015‐12/1/2016), and compared that with pre‐KAS (6/1/2013‐12/3/2014). We modeled DSA‐level DDKT rates with multilevel Poisson regression, adjusting for allocation factors under KAS. Using the model we calculated a novel, improved metric of geographic disparity: the median incidence rate ratio (MIRR) of transplant rate, a measure of DSA‐level variation that accounts for patient casemix and is robust to outlier values. Under KAS, MIRR was _1.751.81_1.86 for adults, meaning that similar candidates across different DSAs have a median 1.81‐fold difference in DDKT rate. The impact of geography was greater than the impact of factors emphasized by KAS: having an EPTS score ≤20% was associated with a 1.40‐fold increase (IRR = _1.351.40_1.45, P < .01) and a three‐year dialysis vintage was associated with a 1.57‐fold increase (IRR = _1.561.57_1.59, P < .001) in transplant rate. For pediatric candidates, MIRR was even more pronounced, at _1.661.92_2.27. There was no change in geographic disparities with KAS (P = .3). Despite extensive changes to kidney allocation under KAS, geography remains a primary determinant of access to DDKT.

     

Kidney accelerated placement project: Outcomes and lessons learned

Opportunities continue to be lost with a high rate of kidneys recovered for transplant but not utilized, particularly those considered less than ideal quality. The Organ Procurement and Transplantation Network (OPTN) Organ Center is tasked with allocating arguably the most difficult-to-place kidneys, and we hypothesized an accelerated placement pathway would increase utilization of kidneys placed by the Organ Center. The Kidney Accelerated Placement (KAP) project, implemented by the Organ Center from July 18, 2019 to July 15, 2020, aimed to offer kidneys with a high kidney donor profile index to programs that had a history of accepting such organs. We compared OPTN kidney match run, donor, and transplant recipient data during the project period and 1 year prior. There was no statistically significant change in the percentage of KAP-eligible donors accepted during the project period (16.4%) compared to the prior year (17.5%). Conversion from acceptance to transplant was higher under KAP (72.7% vs. 71.2%), though not significant. Waiting to accelerate placement after kidneys have been declined by multiple transplant programs locally and regionally is an intervention that may come too late to effectively increase utilization. Transplant rates of nationally shared and marginal kidneys remain a challenge, and future iterations of this project should be investigated.

     

Potential yield of imminent death kidney donation

About 99 000 people are waiting for a kidney in the United States, and many will die waiting. The concept of “imminent death” donation, a type of living donation, has been gaining attention among physicians, patients, and ethicists. We estimated the number of potential imminent death kidney donors at the University of Wisconsin Hospital and Clinics by assessing the number of annual deaths in individuals with normal kidney function. Based on a previous survey suggesting that one‐third of patients might be willing to donate at imminent death, we estimate that between 76 and 396 people in the state of Wisconsin would be medically eligible and willing to donate each year at the time of imminent death. We extrapolated these numbers to all transplant centers in the United States, estimating that between 5925 and 31 097 people might be eligible and willing to donate each year. Our results suggest that allowing donation at imminent death and including discussions about organ donation in end‐of‐life planning could substantially reduce the nation's kidney waiting list while providing many more donors the opportunity to give this gift.     

Changes in Pediatric Renal Transplantation After Implementation of the Revised Deceased Donor Kidney Allocation Policy

In October 2005, the United Network for Organ Sharing (UNOS) implemented a revised allocation policy requiring that renal allografts from young deceased donors (DDs) (<35 years old) be offered preferentially to pediatric patients (<18 years old). In this study, we compare the pre- and postpolicy quarterly pediatric transplant statistics from 2000 to 2008. The mean number of pediatric renal transplants with young DDs increased after policy implementation from 62.8 to 133 per quarter (p < 0.001), reflecting a change in the proportion of all transplants from young DDs during the study period from 0.33 to 0.63 (p < 0.001). The mean number of pediatric renal transplants from old DDs (≥35 years old) decreased from 22.4 to 2.6 per quarter (p < 0.001). The proportion of all pediatric renal transplants from living donors decreased from 0.55 to 0.35 (p < 0.001). The proportion from young DDs with five or six mismatched human leukocyte antigen (HLA) loci increased from 0.16 to 0.36 (p < 0.001) while those with 0 to 4 HLA mismatches increased from 0.18 to 0.27 (p < 0.001). Revision of UNOS policy has increased the number of pediatric renal transplants with allografts from young DDs, while increasing HLA-mismatched allografts and decreasing the number from living donors.     

The cost of procuring deceased donor kidneys: Evidence from OPO cost reports 2013‐2017

Using 5 years of US organ procurement organization (OPO) data, we determined the cost of recovering a viable (ie, transplanted) kidney for each of 51 OPOs. We also examined the effects on OPO costs of the recovery of nonviable (ie, discarded) kidneys and other OPO metrics. Annual cost reports from 51 independent OPOs were used to determine the cost per recovered kidney for each OPO. A quadratic regression model was employed to estimate the relationship between the cost of kidneys and the number of viable kidneys recovered, as well as other OPO performance indicators. The cost of transplanted kidneys at individual OPOs ranged widely from $24 000 to $56 000, and the average was $36 000. The cost of a viable kidney tended to decline with the number of kidneys procured up to 549 kidneys per year and then increase. Of the total 81 401 kidneys recovered, 66 454 were viable and 14 947 (18.4%) were nonviable. The costs of kidneys varied widely over the OPOs studied, and costs were a function of the recovered number of viable and nonviable organs, local cost levels, donation after cardiac death, year, and Standardized Donor Rate Ratio. Cost increases were 3% per year.