Faculty Bibliography

INTRODUCTION/BACKGROUND:Early post-kidney transplant (KT) changes likely impact body composition, resulting in adverse post-KT outcomes. We estimated post-KT trajectories of computed tomography (CT)-based muscle quantity/quality and tested whether they were associated with mortality and death-censored graft loss (DCGL) among frail and nonfrail recipients. METHODS:We leveraged a cohort of 294 adult KT recipients (December 2008-February 2020) with CT measurements (muscle quantity: skeletal muscle index; muscle quality: skeletal muscle radiation attenuation). We used mixed linear regression models to estimate 3-year post-KT muscle quantity/quality trajectories. Cox proportional hazard models quantified the association between time-varying pre-/post-KT muscle mass measurements and post-KT mortality and DCGL. RESULTS:) was associated with elevated mortality risk (aHR: 2.00, 95% CI: 1.08-3.70), but not among nonfrail recipients. Among older (≥65 years) recipients, lower muscle quantity was associated with increased DCGL risk (aHR: 2.70, 95% CI: 1.04-7.04), but not among younger recipients. Lower muscle quality (per 10 HU) was associated with elevated mortality (aHR: 2.23, 95% CI: 1.61-3.08) and DCGL (aHR: 1.90, 95% CI: 1.16-3.12) risk. CONCLUSION/CONCLUSIONS:Lower pre-/post-KT muscle quantity/quality were associated with higher risks of post-KT adverse outcomes. Pre-/post-KT rehabilitation to improve muscle quantity/quality may be an effective clinical intervention to minimize risks of adverse post-KT outcomes.

Given the unique risk profile of kidney transplant recipients (KTRs), characterizing their cardiovascular disease (CVD) risk after COVID-19 remains critical for targeted management. We performed a retrospective analysis of 809 clinically diagnosed symptomatic COVID-19 events among 778 KTRs from one Maryland health system (3/2020-1/2024) to characterize incidence and risk factors of post-COVID-19 CVD. We followed KTRs until composite CVD (acute coronary syndrome (ACS), stroke, heart failure (HF), CVD death), non-CVD death, or one year after COVID-19 and identified risk factors using LASSO-based sub-distribution hazards regression. Incidence of post-COVID CVD was 8.7% at one-year (2.7% ACS, 1.4% stroke, 3.6% HF, and 1.0% CVD death). KTRs with CVD history had higher incidence than those without (19.1% vs 5.0%). Older age, Black race, Hispanic ethnicity, prior CVD, and COVID-19 hospitalization increased post-COVID CVD risk; BMI>30 and treatment with remdesivir decreased post-COVID CVD risk. COVID-19 hospitalization conferred equivalent risk to prior CVD: incidence was 11.2% among KTRs with prior CVD but no hospitalization, 12.0% among KTRs with hospitalization but no prior CVD, 25.2% among KTRs with both, and 1.8% among KTRs with neither. Post-COVID-19 CVD risk was high among KTRs and hospitalization for COVID-19 was as important as having had a prior cardiovascular event.

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.

Kidney transplantation from donors with HIV has recently become standard clinical practice, but the plasma inflammatory profile is not well characterized. Thirty-two cytokines and chemokines were evaluated among donors with HIV (n = 63) and without HIV (n = 41). Wilcoxon rank sum test was used to compare cytokines between groups. Donors with and without HIV were generally similar in terms of characteristics, except those with HIV had a non-significantly lower kidney donor profile index, reflecting better graft survival, creatinine, and body mass index. Most cytokine and chemokine levels were similar between groups. However, median IL-8 levels were higher (p < 0.0015) in donors without HIV (32.6 pg/mL, IQR = 13.8-394.9) compared to donors with HIV (15.1 pg/mL, IQR = 8.4-35.5). There were no significant correlations between cytokine and chemokine concentrations and CD4 counts or HIV viral load. In summary, inflammatory profiles were similar or lower among donors with HIV compared to donors without HIV supporting the safety of this emerging kidney transplantation practice.

OBJECTIVE:Peripheral artery disease (PAD) is a common comorbidity among patients waitlisted for deceased donor kidney transplant (DDKT). However, some centers consider PAD a contraindication for transplant given the higher risk of post-operative complications. We aimed to examine the survival benefit of DDKT among patients with and without PAD. METHODS:We used data from the Scientific Registry of Transplant Recipients (SRTR) from January 2003 to December 2022 to identify all DDK waitlist candidates. Kaplan-Meier survival estimates and multivariable Cox proportional hazards models were used to compare patient mortality for those who received a DDKT versus those remaining on the waitlist, stratified by PAD status. RESULTS:506,785 candidates were listed for adult kidney-only transplant during the study period, of which 8.7% had PAD and 36.0% received a DDKT. After a median follow-up time of 3.21 years from waitlist activation [interquartile range 1.11-7.03 years], mortality varied significantly according to DDKT and PAD status. After adjusting for baseline differences, DDKT was associated with a significantly lower hazard of death compared to remaining on the waitlist, regardless of PAD status [adjusted hazards ratio (aHR) 0.45-0.60, P<0.001]. Further stratifying by sex, race and ethnicity, and diabetes status did not substantially alter these results. CONCLUSION/CONCLUSIONS:PAD includes a spectrum of diseases with varying mortality risks. As captured and dichotomized in the SRTR database, DDKT conferred a similar long-term benefit relative to remaining on the waitlist for candidates with and without PAD. Therefore, PAD should not be an absolute contraindication to DDKT.

Transplantation from donors with hepatitis C virus (HCV) viremia to recipients without HCV-viremia (HCV D⁺/R^-) is common, but no data exist for recipients with HIV or donors with HCV/HIV coinfection. We assessed outcomes of HCV D⁺/R^- transplants within 3 HIV Organ Policy Equity Act studies of HIV⁺ abdominal transplantation to recipients with HIV between 2017 and 2023. Eighteen kidney and 6 liver transplant recipients with HIV received organs from 19 donors with HCV viremia, including 7 with HCV/HIV coinfection. Median recipient age was 58 years, 96% were male, and median waitlist time was 1 year. All recipients had undetectable HIV RNA at time of transplant with median cluster of differentiation 4 count 499 cells/mm³. HCV/HIV-coinfected donors had median cluster of differentiation 4 count 210 cells/mm³, and 4 of the 7 had detectable HIV RNA. HCV treatment with direct-acting antivirals was initiated at median 33 days after transplant and sustained virologic response was achieved in 23 of the 23 treated recipients without HCV-related adverse events; data unavailable for 1 participant. Kaplan-Meier survival analysis demonstrated 100% 1-year and 96% 3-year survival. Graft survival was 96% at 1 and 3 years. HCV D⁺/R^- abdominal transplantation, including donors with HCV/HIV coinfection, demonstrates favorable patient and graft survival in recipients with HIV and is a viable strategy to increase organ utilization.

[This corrects the article DOI: 10.1016/j.lana.2024.100895.].

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.

Older (aged ≥55 years) kidney transplant (KT) recipients diagnosed with a sleep disorder after transplantation may be at increased risk for developing dementia. Using the United States Renal Data System/Medicare claims (2010-2020), we identified 16 573 older KT recipients with a functioning graft 1-year post-KT. First-time sleep disorders and newly prescribed sleep medications were ascertained within the first year post-KT. We used cause-specific hazard models to estimate the adjusted hazard ratio of diagnosed dementia with inverse probability of treatment weights. Overall, 3615 (21.8%) KT recipients were newly diagnosed with sleep disorders. Recipients diagnosed with a sleep disorder had a 1.32-fold increased risk for dementia (95% CI:1.15-1.51); those with insomnia had a 1.56-fold increased risk (95% CI:1.20-2.03). Of those diagnosed with insomnia, only 7.5% underwent cognitive behavioral therapy for insomnia. Of the recipients, 12.9% with a sleep disorder were prescribed sleep medications. Recipients prescribed sleep medication had a 1.44-fold increased risk for dementia (95% CI:1.16-1.77). Those prescribed zolpidem, the most commonly prescribed medication (80.1%), had a 1.41-fold increased risk (95% CI:1.12-1.78) for dementia; those prescribed other sleep medications had 3.13-fold (95% CI:1.41-6.98) increased risk for dementia. Post-KT sleep disorders are modifiable dementia risk factors; medication-associated dementia risk should be weighed against other therapies such as cognitive behavioral therapy for insomnia during management.