Bekir Tanriover

Viral infections influence every stage of the kidney transplantation continuum, shaping immunologic risk, graft outcomes, and long term patient survival. Pre transplant serologic assessments guide critical decisions, including vaccinations, the avoidance of lymphocyte depleting induction in Epstein-Barr virus (EBV) mismatched candidates and the selection of Cytomegalovirus (CMV) prophylaxis tailored to donor–recipient serostatus. Acceptance of hepatitis C viremic donor organs has significantly reduced wait times, while human immunodeficiency virus (HIV) positive donor organs remain restricted to HIV positive recipients. Post transplant, viral pathogens are major drivers of morbidity: CMV functions as an immunomodulator that increases susceptibility to rejection and opportunistic fungal infections, and routine surveillance for CMV and BK viremia is essential, especially following rejection therapies. BK virus nephropathy, adenovirus nephropathy, and JC virus nephropathy can lead to progressive allograft dysfunction. Additionally, COVID 19 and parvovirus infections have been associated with collapsing focal segmental glomerulosclerosis (FSGS) and severe graft injury. Persistent viral infections and virus associated glomerulopathies contribute to chronic graft loss, while EBV driven post transplant lymphoproliferative disorder (PTLD) remains a significant cause of cancer related mortality. Transplant recipients are also at increased risk for persistent human papillomavirus infection (HPV) and progression to anogenital and oropharyngeal malignancies. Finally, donor derived viral infections, including rabies, West Nile virus (WNV), and lymphocytic choriomeningitis virus (LCMV), though rare, are well described in the literature. Collectively, these viral complications substantially impact morbidity, graft survival, and overall mortality in kidney transplant recipients.

The persistent imbalance between organ supply and demand poses a significant challenge for the lifesaving treatment of transplantation. This study introduces innovative targeted priority mechanisms inspired by the Eurotransplant Senior Program (ESP), designed to bridge the supply-demand gap while optimizing the matching between organs and recipients without mandating offer acceptance. These mechanisms diverge from traditional prioritization by offering voluntary participation and granting explicit priority to disadvantaged patients for a specified range of organs, provided they restrict their offer acceptance to this set. Using a comprehensive queueing model, our study analyzes the strategic decisions of waitlisted candidates under targeted priority mechanisms in equilibrium, establishing the optimal program design. Our evaluation of these mechanisms’ impact on social welfare underscores their potential to improve overall welfare without adversely affecting any patient group. The practical applicability and impact of these mechanisms are demonstrated through a case study within the U.S. kidney allocation system, using a clinically detailed simulation model targeting elderly patients aged 65 and above. Simulation outcomes reveal a significant participation rate (70%) even when the program offers priority over kidneys that are conventionally perceived as marginal. Furthermore, our findings highlight the mechanisms’ potential to increase transplants by up to 920, decrease nonuse by 25%, and prevent up to 193 waitlist deaths annually compared with the current system. Improvements in the outcomes of even nonelderly patients highlight the mechanisms’ potential to comprehensively address organ underutilization and improve organ-recipient matching in a real-world context. This paper was accepted by Nicos Savva, healthcare management. Funding: This work was supported by the Division of Civil, Mechanical and Manufacturing Innovation [Grant 2339767]. This work was supported in part by the Health Resources and Services Administration [Contract HHSH250-2019-00001C]. Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2024.05724 .

Background: During the COVID-19 pandemic, uncertainty regarding the safety of kidneys from COVID-19-positive donors led to a reduction in kidney transplants and increased organ non-use in the United States. This study aims to evaluate whether donor COVID-19 positivity is associated with one-year post-transplant estimated glomerular filtration rate (eGFR) among kidney transplant recipients. Methods: This retrospective cohort study used data from the United States Organ Procurement and Transplantation Network (OPTN) 2020–2024. Donor COVID-19 status was determined by the SARS-CoV-2 nucleic acid amplification technique (NAT) and antibody test results. The main outcome was recipients’ one-year eGFR, estimated by the CKD-EPI 2021 formula. Linear regression models were used to compare the mean one-year eGFR among donor COVID-19 groups, adjusted by inverse probability of treatment weights. Interaction terms of donor acute kidney injury status and race were assessed to evaluate effect modification. Results: Among 38,199 included kidney transplant recipients, 1090 (2.9%) received kidneys from donors with active COVID-19 infection, 423 (1.1%) from donors with resolved infection, and 36,686 (96.0%) from COVID-19-negative donors. After weighting and adjustment, there was no significant difference in one-year eGFR for recipients of kidneys from donors with active COVID-19 (mean difference, 0.05 [95% CI, −1.08 to 1.18]) or resolved infection (mean difference, −0.27 [95% CI, −2.19 to 1.64]) compared with COVID-19-negative donors. Neither donor AKI nor donor race modified the association between donor COVID-19 status and one-year eGFR. Conclusions: This study suggests that kidneys from COVID-19-positive donors may be a viable option without compromising short-term allograft function as measured by 1-year eGFR.

Key Points: We assessed whether an initial donor-derived cell-free DNA elevation during routine surveillance was associated with allograft dysfunction and loss in kidney transplant recipients. Intermediate and high donor-derived cell-free DNA states were independently associated with 3.7-fold and 6.4-fold higher risks of allograft loss, respectively. Persistently low donor-derived cell-free DNA levels were associated with low rates of rejection and allograft loss, identifying a low-risk population. Background: Although donor-derived cell-free DNA (dd-cfDNA) correlates with histologic rejection and injury severity, its association with long-term graft outcomes has yet to be well established in kidney transplant recipients. We hypothesize that among patients monitored with dd-cfDNA, an initial elevation may be associated with subsequent allograft dysfunction and loss. Methods: The Kidney Allograft Outcomes AlloSure Registry is a prospective, multicenter cohort of 1743 adult kidney transplant recipients from 56 US centers; this analysis included 1258 patients who initiated dd-cfDNA surveillance 15–60 days post-transplant with up to 3-year follow-up. A multistate model was applied to characterize transitions from a low dd-cfDNA state (no elevations) to intermediate (0.5%–1.0% with ≥61% relative change value) or high (≥1.0%) dd-cfDNA states, and their unadjusted and covariate-adjusted associations with allograft loss or all-cause death were quantified using hazard regression models. Results: Within 3 years, 36% of patients transitioned to an elevated dd-cfDNA state (intermediate n =216; high n =233). Allograft dysfunction by 36 months occurred significantly more often in patients with dd-cfDNA elevations despite preserved allograft function at the time of elevation (eGFR ≥60 ml/min per 1.73 m ² in 42% of intermediate and 33% of high), consistent with subclinical injury. Transitions from low to elevated dd-cfDNA states were strongly associated with subsequent allograft loss (adjusted hazard ratios, 3.70 [95% confidence interval [CI], 1.38 to 9.90] for intermediate; 6.36 [95% CI, 2.80 to 14.42] for high), while mortality did not differ by dd-cfDNA state. Conclusions: Initial dd-cfDNA elevations exceeding established thresholds were independently associated with higher risks of allograft dysfunction and loss across both elevation categories, whereas patients who remained in the low dd-cfDNA state experienced favorable outcomes.