Abstract
This study uses US national data to examine Epstein-Barr virus–seronegative donor kidney use among Epstein-Barr virus–seronegative children.
Epstein-Barr virus (EBV) increases risk of posttransplant lymphoproliferative disorder (PTLD), a rare neoplastic complication associated with high morbidity and mortality.1 Incidence of PTLD is highest among EBV-seronegative recipients (R−) receiving organs from EBV-seropositive donors (D+).2 Children are especially vulnerable to PTLD because approximately 40% to 50% are EBV seronegative, whereas less than 10% of adults are EBV seronegative.1,3 An estimated 7% to 15% of children who undergo a D+/R− kidney transplant develop PTLD.2,3 Infection with EBV after transplant and PTLD generally require a reduction in immunosuppression and aggressive therapies (eg, rituximab, chemotherapy), contributing to increased risk of graft loss and decreased patient survival.1,2,4 Transplanting organs from EBV-seronegative donors into seronegative recipients significantly reduces risk of PTLD.3
The US kidney allocation system prioritizes children to receive kidneys from deceased donors with a Kidney Donor Profile Index (KDPI) score less than 35% because they have superior predicted graft survival.5 The KDPI combines several donor factors to estimate likelihood of graft failure after transplant. However, organ allocation does not prioritize D−/R− transplants. Using US national data, we examined D− kidney use among EBV-seronegative children.
Methods
This cohort study used Organ Procurement and Transplantation Network data to examine national organ use in the US by assembling a cohort of deceased donor kidney transplant recipients from January 1, 2018, to December 31, 2023. Exposure of interest was donor EBV serostatus. Outcome was transplant into children (<18 years at listing) and adult recipients, stratified by recipient EBV serostatus. Donors with KDPI score greater than or equal to 35% and donors and children with unknown EBV serostatus were excluded. Because pediatric transplant centers are selective regarding donor quality, we defined an ideal pediatric-quality kidney as procured from a brain-dead donor younger than 35 years, with terminal creatinine level less than 1.5 mg/dL, no diabetes or hypertension history, and low infection risk.6 The University of Pennsylvania institutional review board approved this study. R version 4.5.1 (R Core Team) was used for data analysis.
Results
During the study period, at least 1 kidney was transplanted from 61 368 deceased donors, of whom 24 639 (40.1%) had KDPI score less than 35% and documented EBV serostatus. Among donors meeting inclusion criteria, 2421 (9.8%) were EBV seronegative, resulting in 4730 transplanted kidneys. Compared with seropositive donors, seronegative donors were younger (median age, 22 vs 29 years) and more often had ideal pediatric-quality kidneys (44.2% vs 31.4%) (Table 1). Among 24 639 donors, 1071 were both EBV seronegative and with ideal pediatric-quality kidneys.
Table 1. Demographic and Clinical Characteristics of Deceased Donors With KDPI Score Less Than 35% Stratified by Epstein-Barr Virus (EBV) Serostatus.
| Donor factors | EBV serostatus, No. (%) | Standardized mean difference | |
|---|---|---|---|
| Negative (D−) | Positive (D+) | ||
| No. of donorsa (N = 24 639) | 2421 (9.8) | 22 218 (90.2) | |
| No. of kidneys transplanteda (N = 48 005) | 4730 (9.9) | 43 275 (90.1) | |
| Age, median (IQR), y | 22 (17-29) | 29 (22-36) | 0.611 |
| Sex | |||
| Male | 1796 (74.2) | 15 387 (69.3) | 0.110 |
| Female | 625 (25.8) | 6831 (30.7) | |
| Race | |||
| Asian | 46 (1.9) | 433 (1.9) | 0.004 |
| Black | 142 (5.9) | 2339 (10.5) | 0.171 |
| Hispanic | 262 (10.8) | 4135 (18.6) | 0.221 |
| Otherb | 40 (1.7) | 416 (1.9) | 0.017 |
| White | 1931 (79.8) | 14 895 (67.0) | 0.291 |
| Creatinine level ≥1.5 mg/dL | 405 (16.7) | 3620 (16.3) | 0.012 |
| Hypertension | 121 (5.0) | 1244 (5.6) | 0.027 |
| Diabetes | 44 (1.8) | 322 (1.4) | 0.029 |
| Ideal pediatric-quality kidney | 1071 (44.2) | 6976 (31.4) | 0.267 |
| Donation after circulatory death | 565 (23.3) | 4414 (19.9) | 0.084 |
| KDPI score, median (IQR), %c | 12 (5-23) | 17 (9-26) | 0.310 |
Abbreviations: EBV, Epstein-Barr virus; KDPI, Kidney Donor Profile Index. Blank cells indicate not applicable.
The EBV serostatus was unknown for 2285 kidneys from deceased donors with a KDPI score less than 35%, and they were excluded from the analyses; 42 of these kidneys were transplanted into EBV-seronegative children.
Other race included donors who were Pacific Islander, American Indian or Alaska Native, Arab, Indian subcontinent, and other race categories. The race and ethnicity of deceased donors were reported by organ procurement organizations (OPOs), and the ascertainment of race and ethnicity may vary between OPOs.
The KDPI is a risk score that ranges from 0% to 100%, summarizing the likelihood of graft survival for deceased donor kidneys. Lower KDPI scores indicate longer expected graft survival after transplant.
During the same period, 1399 of 3330 children (42.0%) who underwent a kidney transplant were EBV seronegative. Among EBV-seronegative children, 188 (13.4%) underwent D−/R− transplant and 1211 (86.6%) underwent D+/R− transplant (Table 2); 3778 adults underwent D−/EBV-seropositive recipient transplant.
Table 2. Epstein-Barr Virus (EBV) Donor and Recipient Serostatus Stratified by Recipient Age at Transplant.
| Recipient age category, ya | Donor/recipient EBV serostatus, No. (%) | |||
|---|---|---|---|---|
| D−/R− | D+/R− | D−/R+ | D+/R+ | |
| All children (0 to <18) (N = 3330)b | 188 (5.6) | 1211 (36.4) | 227 (6.8) | 1704 (51.2) |
| 0-10 (n = 1245) | 113 (9.1) | 632 (50.7) | 63 (5.1) | 437 (35.1) |
| 11-17 (n = 2085) | 75 (3.6) | 579 (27.8) | 164 (7.9) | 1267 (60.8) |
| All adults (≥18)b (N = 42 784) | 353 (0.8) | 2473 (5.8) | 3778 (8.8) | 36 180 (84.6) |
| 18-29 (n = 5179) | 81 (1.6) | 494 (9.5) | 519 (10.0) | 4085 (78.9) |
| ≥30 (n = 37 605) | 272 (0.7) | 1979 (5.3) | 3259 (8.7) | 32 095 (85.3) |
Abbreviations: D−, donor seronegative; D+, donor seropositive; R−, recipient seronegative; R+, recipient seropositive.
Recipients were stratified by age because younger transplant recipients are more likely to be EBV seronegative and more at risk of developing EBV-associated neoplastic complications.
The EBV serostatus was unknown for 96 children and 1891 adult recipients, and they are excluded from the table.
Discussion
Despite well-documented risks of EBV infection after transplant, less than 14% of EBV-seronegative children in this national cohort received an EBV-seronegative kidney. Most EBV-seronegative kidneys were transplanted into EBV-seropositive adults, who are at low risk for PTLD.2,4
Based on the results presented, the number of available EBV-seronegative kidneys in the US exceeded the number of EBV-seronegative children awaiting kidney transplant, thus providing an opportunity to increase D−/R− transplants and reduce the burden of EBV-associated PTLD among children. An approach to facilitate D−/R− transplants is to award priority to EBV-seronegative children for EBV-seronegative organs during organ allocation.
This study has limitations. It could not determine whether organs were declined for children (due to donor comorbidities, anatomic concerns, or other reasons) nor how many immunologically compatible children awaiting transplant were within allocation boundaries when organs were offered. Although additional simulation work is required to determine feasibility and examine how this approach might affect other allocation priorities for children (eg, human leukocyte antigen matching), as well as access for other candidates, the relatively small number of EBV-seronegative children awaiting kidney transplant suggests that policies facilitating D−/R− transplants might have a limited effect on others. Policymakers should consider the feasibility of prioritizing D−/R− transplants to reduce the burden of PTLD among children.
Data Sharing Statement
References
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Supplementary Materials
Data Sharing Statement
