Faculty Bibliography

Pediatric deceased donor kidneys with acute kidney injury (ped-AKI) are at increased risk for non-utilization. To evaluate the post-transplant outcomes of ped-AKI recipients, we conducted a retrospective cohort study, comparing 17,731 adult recipients of kidneys from pediatric donors without AKI (ped-non-AKI, terminal serum creatinine (SCr)<1 mg/dL) to 1,589 ped-AKI recipients (SCr≥2 mg/dL). We used weighted logistic regression to estimate the association between ped-AKI and delayed graft function (DGF), and weighted Cox regression to estimate the association between ped-AKI and primary non-function (PNF) and all-cause graft failure (ACGF). Ped-AKI kidney recipients were at 6.0-fold (aOR=_5.325.98_6.72), 1.9-fold (aHR=_1.361.87_2.58), and 1.4-fold (aHR=_1.161.43_1.76) higher risk of DGF, PNF, and 1-year ACGF compared to ped-non-AKI recipients. En bloc ped-AKI recipients were at 5.6-fold (aOR=_3.295.57_9.43), 3.3-fold (aHR=_1.723.25_6.15), and 2.9-fold (aHR=_1.702.92_5.01) higher risk of DGF, PNF, 1-year ACGF compared to en bloc ped-non-AKI recipients. Among recipients of single kidneys from donors<20kg, ped-AKI recipients were at 8.9-fold (aOR=_4.348.87_18.12), 5-fold (aHR=_1.694.99_14.75), and 3.4-fold (aHR=_1.473.44_8.05) higher risk of DGF, PNF, 1-year ACGF compared to ped-non-AKI recipients. Ped-AKI kidney recipients have higher risks of early graft complications and failure. Risks are greatest for recipients of single kidneys from donors<20kg. Careful recipient selection and counseling are prudent when considering ped-AKI kidney offers.

Normothermic machine perfusion (NMP) may increase utilization of non-ideal donor kidneys through improved preservation and assessment. We assessed the use of a centralized perfusion service to rescue declined kidneys for transplant. Kidneys that exhausted standard OPTN allocation underwent 2 hours of NMP for additional assessment. The primary outcome was rescue for transplantation. Outcomes of NMP kidneys were compared to non-NMP kidneys transplanted during the study period at the same transplant centers. NMP was performed on 104 declined kidneys, and 94 (90%) were rescued for transplant. NMP donors were older, with a higher kidney donor profile index (KDPI) compared to non-NMP donors. Cold ischemia time was significantly longer in the NMP cohort (median 37.6 vs. 22.1 hours, p<0.001). The weighted percentage of delayed graft function (DGF) was 26.3% in the NMP group vs 60.2% in the non-NMP group (p=0.023). Overall graft survival was similar between the groups. With the use of a centralized NMP service, kidneys declined based on standard clinical parameters may be evaluated, rescued, and successfully transplanted. Kidneys undergoing NMP experienced significantly lower rates of DGF compared to non-NMP kidneys. Additional follow up is needed to determine the effects of NMP on long-term graft function.

We sought to understand the potential impacts of a rapidly evolving donor pool on the annual recalibration of the kidney donor profile index (KDPI). Using OPTN data, we examined the kidney donor risk index (KDRI) among deceased kidney donors recovered 2011-2024. We mimicked the OPTN's annual re-mapping process to measure the KDRI-to-KDPI calibration drift and used Cox regression to translate this drift into all-cause graft failure rate differences. The 50th/75th/95th KDRI percentile among recovered donors rose from 1.19/1.47/2.0 in 2011 to 1.40/1.77/2.36 in 2024. For donors with the same KDRI, the KDPI assigned in 2024 was as much as 13 points lower than the KDPI assigned in 2012. Holding other factors constant, the KDRI-KDPI calibration shift equated to 7 years of increased age (65 vs. 58) for KDPI 86% donors. Five-year graft failure risk was 9% higher (RR: _1.0871.093_1.097) for a kidney assigned a KDPI of 86% in 2024 versus 2012. Organ recovery practices have changed. The relationship between KDPI and organ quality has become a moving target, complicating shared decision-making and altering the meaning of allocation policy thresholds. Alternative solutions to annually remapping KDPI, such as establishing a fixed reference cohort or migrating away from KDPI, could be considered.

BACKGROUND:Transplant waitlist registrants in the United States may be delisted because of receipt of a transplant abroad. Although not universally unethical, "travel for transplantation" poses risks to posttransplant care. To better understand this phenomenon, this study identifies temporal trends, geographic patterns, and demographic factors associated with cross-border transplantation. METHODS:Using Scientific Registry of Transplant Recipients data, we identified 818 US waitlist candidates who were removed because of transplantation abroad between 2010 and 2023. We described recipient characteristics overall, by organ, and by top transplant destinations. We used a Cox regression framework to identify characteristics associated with waitlist removal due to transplantation abroad. RESULTS:Transplants abroad averaged 58.4 per year. Incidence peaked at 80 transplants in 2017, with an upward trend after 2021. Kidney transplants made up 92.1% of cases. The most common destinations were the Philippines (19.8%), India (16.5%), Mexico (9.4%), China (8.4%), and Iran (4.4%). India and Mexico experienced the smallest drop-off during the height of the COVID-19 pandemic 2020-2021. Most recipients were US citizens (65.0%) or residents (23.5%). Female (adjusted hazard ratio [aHR], 0.520.610.71; P < 0.001) and Black candidates (aHR, 0.120.180.26; P < 0.001) were less likely to travel abroad compared with Asian candidates (aHR, 5.927.108.52; P < 0.001). Nonresidents (aHR, 6.708.6911.26; P < 0.001) and, among registrations in 2012 or later, nonresidents who traveled to the United States for transplantation (aHR, 27.2738.9155.50; P < 0.001) had a greater chance of undergoing transplantation abroad. CONCLUSIONS:Understanding patterns of international travel for transplantation is key not only for preventing resource drains from destination countries but also for providing adequate posttransplant care for recipients.

Procurement biopsies are routinely obtained in the United States to evaluate kidneys considered for transplantation, but some argue that they may contribute to kidney nonutilization. Historically, biopsy decisions have been left solely to the discretion of organ procurement organizations (OPOs) and transplant centers. In September 2022, an organ procurement and transplantation network (OPTN) policy designating donors meeting specific clinical criteria as "biopsy-required" went into effect. Using OPTN data from 1 year before and after policy implementation, we used causal inference methods to estimate the policy's impacts on biopsy practices and kidney utilization. The overall biopsy rate remained stable at 62%, rising from 90.6% to 95.8% (P < .001) among biopsy-required kidneys while falling from 49.1% to 43.4% (P < .001) among biopsy-optional kidneys. After adjusting for changing donor characteristics, the policy was associated with a 5% decline in the biopsy rate (adjusted risk ratio = 0.95; P = .007). The overall kidney nonuse rate rose from 27.2% to 28.7%. After accounting for changes in donor characteristics, the policy was not associated with elevated nonuse (adjusted risk ratio = 0.96, P = .06). Although most OPOs are now biopsying nearly all required kidneys, practices still vary widely regarding biopsy-optional kidneys. No correlation was found between OPO-level changes in adjusted biopsy and nonuse rates (ρ = 0.05, P = .70). The OPTN policy has partially standardized biopsy practices without harming kidney utilization.

BACKGROUND AND HYPOTHESIS/OBJECTIVE:Hepatitis C virus (HCV) positive-to-negative kidney transplants (KT) require direct acting antiviral therapy, but the optimal timing and duration remain unclear. We hypothesized that 14-day prophylactic course of glecaprevir/pibrentasvir 300/120 mg (GLE/PIB) would be safe and effective at treating donor-derived HCV viremia. METHODS:This was a prospective, single-center, single-arm, open-label pilot study. 20 adult HCV negative recipients of HCV nucleic acid amplification test positive deceased-donor kidneys (HCV positive-to-negative) received a 14-day course of GLE/PIB, with the first dose pre-transplant. HCV RNA viral loads (VL) were monitored on post-operative days (POD) 1, 3, 7, and 13. If VL was undetectable on POD 13, GLE/PIB was stopped, and if detectable, GLE/PIB was continued to complete an 8-week course. Surveillance monitoring continued after treatment to ensure sustained viral response (SVR). The primary outcome was efficacy of 14-day prophylactic GLE/PIB. Secondary outcomes included patient and allograft survival, the incidence, timing, and clearance of HCV viremia, and safety events. RESULTS:7/20 subjects (35%) never developed detectable HCV viremia. Only one subject had a detectable, but nonquantifiable, VL on POD 13 and completed an 8-week course. All subjects achieved SVR 12 weeks post-treatment with no relapses through 1-year follow-up. Mean time to undetectable HCV RNA VL was 10.5 (±4.7) days and mean peak VL was 371 (±715) copies/mL. 6-month and 1-year patient and allograft survival were 100% and 95%. CONCLUSION/CONCLUSIONS:A 14-day course of prophylactic GLE/PIB is safe and effective for HCV positive-to-negative KT and may prevent HCV transmission or significantly reduce the VL for those with detectable transmission allowing for rapid clearance within 2 weeks.

Human leukocyte antigen-level matching in US kidney allocation has been deemphasized due to its role in elevating racial disparities. Molecular matching based on eplets might improve risk stratification compared to antigen matching, but the magnitude of racial disparities in molecular matching is not known. To assign eplets unambiguously, we utilized a cohort of 5193 individuals with high-resolution allele-level human leukocyte antigen genotypes from the National Kidney Registry. Using repeated random sampling to simulate donor-recipient genotype pairings based on the ethnic composition of the historical US deceased-donor pool, we profiled the percentage of well-matched donors available for candidates by ethnicity. The prevalence of well-matched donors with 0-DR/DQ eplet mismatch was 3-fold less racially disparate for Black and Asian candidates and 2-fold less for Latino candidates compared to 0-ABDR antigen mismatches. Compared to 0-DR antigen mismatch, 0-DR eplet mismatch was 1.33-fold more racially disparate for Asian and 1.28-fold more for Latino, with similar disparity for Black candidates, whereas 0-DQ eplet mismatch reduced disparities, showing 1.26-fold less disparity for Black, 1.14-fold less for Latino, but 1.26-fold higher for Asian candidates. The prevalence of well-matched donors for candidates of different ethnicities varied according to which molecules were chosen to define a low-risk match.

BACKGROUND:Given the cardiovascular, renal, and survival benefits of GLP-1 receptor agonists for diabetes, these agents could be effective among kidney transplant recipients. However, kidney transplant recipients are distinct from GLP-1 receptor agonist trial participants, with longer diabetes duration and severity, greater end-organ damage, increased cardiovascular risk, and multimorbidity. We examined GLP-1 receptor agonist real-world effectiveness and safety in kidney transplant recipients with diabetes. METHODS:This USA-based retrospective cohort study included kidney transplant recipients with type 2 diabetes at transplantation and Medicare as their primary insurance from a national registry linked with Medicare claims. Post-transplantation GLP-1 receptor agonist use was identified through Medicare claims. Death-censored graft loss was estimated using the Fine-Gray sub-distribution hazard model and extended Cox models were used for mortality and safety endpoints. Models incorporated inverse probability of treatment weights. To further test whether bias could affect the main results, a cohort was created in which each GLP-1 receptor agonist user was matched with a kidney transplant recipient who had not started a GLP-1 receptor agonist, was alive with a functioning graft, and had accrued the same amount of post-transplant survival time. FINDINGS/RESULTS:Between Jan 1, 2013 and Dec 31, 2020, we identified 44 536 first time kidney transplant recipients with Medicare as primary payer in the 6 months before and at transplantation. 24 192 patients were excluded as they did not have type 2 diabetes. 2328 patients were ineligible (1916 had missing values and 412 used GLP-1 receptor agonists before transplantation). The primary cohort thus consisted of 18 016 kidney transplant recipients with diabetes. Of these patients, 1969 (10·9%) had at least one GLP-1 receptor agonist prescription filled post-transplant. Compared with patients who had not received a GLP-1 receptor agonist, GLP-1 receptor agonist users were younger (median age at transplant 57 years [IQR 49-64] vs 60 years [51-66], p<0·0001) and more likely to be female (786 [39·9%] vs 5645 [35·2%], p<0·0001). Among GLP-1 receptor agonist users, 552 [28·0%] were non-Hispanic White, 703 [35·7%] were non-Hispanic Black, and 568 [28·8%] were Hispanic. The 5-year unadjusted cumulative incidence of death-censored graft loss from a cohort matched on survival time before GLP-1 receptor agonist initiation was 6·0% for GLP-1 receptor agonist users and 10·7% for non-users (Gray's test p=0·004). The 5-year unadjusted cumulative incidence for mortality from a cohort matched on survival time before GLP-1 receptor agonist initiation was 17·0% for GLP-1 receptor agonist users and 25·8% for non-users (log-rank p=0·0006). The 5-year unadjusted cumulative incidence for mortality was 13·5% for GLP-1 receptor agonist users and 19·9% for non-users (log-rank p<0·0001). GLP-1 receptor agonist use was associated with a 49% lower incidence of death-censored graft loss (adjusted subhazard ratio [aSHR] 0·51, 95% CI 0·36-0·71; p=0·0001) and 31% lower mortality (adjusted hazard ratio [aHR] 0·69, 95% CI 0·55-0·86; p=0·001). Inferences were robust when matched on survival time (death-censored graft loss aSHR 0·53, 95% CI 0·37-0·75; p=0·0005; mortality aHR 0·70, 95% CI 0·55-0·88; p=0·003). Safety endpoints were rare and not associated with GLP-1 receptor agonists, with the exception of diabetic retinopathy (aHR 1·49, 1·11-2·00; p=0·008). INTERPRETATION/CONCLUSIONS:GLP-1 receptor agonists were associated with better graft and patient survival. Clinical trials are needed to confirm these findings. FUNDING/BACKGROUND:National Institutes of Health.