Faculty Bibliography

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.

BACKGROUND:Sarcopenia has been associated with adverse postoperative outcomes in older age cohorts, but has not been assessed in older adults with inflammatory bowel disease (IBD). Further, current assessments of sarcopenia among all aged individuals with IBD have used various measures of muscle mass as well as cutoffs to define its presence, leading to heterogeneous findings. METHODS:In this single-institution, multihospital retrospective study, we identified all patients aged 60 years and older with IBD who underwent disease-related intestinal resection between 2012 and 2022. Skeletal Muscle Index (SMI) and Total Psoas Index (TPI) were measured at the superior L3 endplate on preoperative computed tomography scans and compared through receiver operating characteristic curve. We then performed multivariable logistic regression to assess risk factors associated with an adverse 30-day postoperative outcome. Our primary outcome included a 30-day composite of postoperative mortality and complications, including infection, bleeding, cardiac event, cerebrovascular accident, acute kidney injury, venous thromboembolism, reoperation, all-cause rehospitalization, and need for intensive care unit-level care. RESULTS:A total of 120 individuals were included. Overall, 52% were female, 40% had ulcerative colitis, 60% had Crohn's disease, and median age at time of surgery was 70 years (interquartile range: 65-75). Forty percent of older adults had an adverse 30-day postoperative outcome, including infection (23%), readmission (17%), acute kidney injury (13%), bleeding (13%), intensive care unit admission (10%), cardiac event (8%), venous thromboembolism (7%), reoperation (6%), mortality (5%), and cerebrovascular accident (2%). When evaluating the predictive performance of SMI vs TPI for an adverse 30-day postoperative event, SMI had a significantly higher area under the curve of 0.66 (95% CI, 0.56-0.76) as compared to 0.58 (95% CI, 0.48-0.69) for TPI (P = .02). On multivariable logistic regression, prior IBD-related surgery (adjusted odds ratio [adjOR] 6.46, 95% CI, 1.85-22.51) and preoperative sepsis (adjOR 5.74, 95% CI, 1.36-24.17) significantly increased the odds of adverse postoperative outcomes, whereas increasing SMI was associated with a decreased risk of an adverse postoperative outcome (adjOR 0.88, 95% CI, 0.82-0.94). CONCLUSIONS:Sarcopenia, as measured by SMI, is associated with an increased risk of postoperative complications among older adults with IBD. Measurement of SMI from preoperative imaging can help risk stratify older adults with IBD undergoing intestinal resection.

RATIONALE & OBJECTIVE/OBJECTIVE:Despite national efforts, the uptake of home dialysis (peritoneal dialysis or home hemodialysis) remains low. Characteristics of the built environment may differentially impact home dialysis use. STUDY DESIGN/METHODS:Retrospective cohort study (2010-2019). SETTING & PARTICIPANTS/METHODS:1,103,695 adults (aged≥18 years) initiating dialysis in the US Renal Data System. EXPOSURE/METHODS:We examined 3 built environment domains based on residential ZIP code: (1) medically underserved areas (MUAs), defined as neighborhoods with limited primary care access; (2) distance to the nearest dialysis facility; and (3) distribution of housing characteristics (structure and overcrowding). OUTCOME/RESULTS:Uptake of home dialysis modalities at dialysis initiation. ANALYTICAL APPROACH/METHODS:We quantified associations between built environment characteristics and home dialysis initiation using multilevel logistic regression stratified by urbanicity type (urban, suburban, small-town, and rural). RESULTS:Among adults initiating dialysis, 40.8% lived in MUAs. Across ZIP codes, the mean percentage of overcrowded housing was 4.2% (SD, 4.7%), and the percentage of detached housing was 61.1% (SD, 21.1%); mean distance to the nearest dialysis facility was 5.5km (SD, 9.1km). Living in MUAs was associated with reduced home dialysis use only in urban (OR, 0.94; 95% CI, 0.91-0.96) and suburban (OR, 0.92; 95% CI, 0.89-0.94) areas. Similarly, housing overcrowding was associated with decreased home dialysis use only in urban (OR, 0.88; 95% CI, 0.86-0.89) and suburban (OR, 0.91; 95% CI, 0.90-0.93) areas. Longer distance to a dialysis facility was the most salient neighborhood factor associated with increased home dialysis use in small towns (OR, 1.14; 95% CI, 1.12-1.16) and rural areas (OR, 1.17; 95% CI, 1.15-1.19). LIMITATIONS/CONCLUSIONS:Housing characteristics were measured at the ZIP code level. CONCLUSIONS:Built environment characteristics associated with home dialysis uptake vary by urbanicity. Policies should address built environment barriers that are specific to urbanicity level. For example, increasing the frequency of dialysate delivery schedules could address housing space constraints in urban and suburban areas, and promoting home dialysis might be more effective for patients living far from dialysis centers in small-town and rural areas.

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.

Unauthorized immigrants and permanent residents may experience challenges in accessing kidney transplantation due to limited healthcare access, socioeconomic and cultural barriers. Understanding the United States (US) national landscape of kidney transplantation for non-citizens may inform policy changes. To evaluate this, we utilized two cohorts from the US national registry (2013-2023): 287,481 adult candidates for first transplant listing and 190,176 adult first transplant recipients. Citizenship was categorized as US citizen (reference), permanent resident, and presumed unauthorized immigrant. Negative binomial regression was used to quantify the incidence rate ratio over time by citizenship status. Cause-specific hazards models, with clustering at the state of listing/transplant, were used to calculate the adjusted hazard ratio of waitlist mortality, kidney transplant, and post-transplant outcomes (mortality/death-censored graft failure) by citizenship category. The crude proportion of presumed unauthorized immigrants listed increased over time (2013: 0.9%, 2023:1.9%). However, after accounting for case mix and waitlist size, there was no change in listing over time. Presumed unauthorized immigrants were less likely to experience waitlist mortality (adjusted Hazard Ratio 0.54, 95% Confidence Interval: 0.46-0.62), were more likely to obtain deceased donor kidney transplant (1.11: 1.05-1.18), but less likely to receive live donor (0.80: 0.71-0.90) or preemptive kidney transplant (0.52: 0.43- 0.62). When stratified by insurance status, presumed unauthorized immigrants on Medicaid were less likely to receive deceased donor kidney transplants compared to their citizen counterparts; however, presumed unauthorized immigrants with Private insurance or Medicare were more likely to receive deceased donor kidney transplants. Presumed unauthorized immigrants were less likely to experience post-transplant death (0.56: 0.43-0.69) and graft failure (0.69: 0.57-0.84). Residents had similar pre- and post-transplant outcomes. Despite the barriers to kidney transplantation faced by presumed unauthorized immigrants and residents in the US, better post-transplant outcomes for presumed unauthorized immigrants compared to citizens persisted, even after accounting for differences in patient characteristics.

Transplantation of kidneys from donors with HIV to recipients with HIV (HIV D+/R+) has been shown to be safe and effective, but there is a unique risk of donor-derived HIV-superinfection (HIV-SI) in these recipients. Recipients from a multicenter observational HIV D+/R+ study were examined for HIV-SI using site-directed next-generation sequencing (Illumina). Eighteen HIV D+/R+ kidney transplant recipients had both baseline and follow-up samples that successfully amplified. One recipient was confirmed to have experienced donor-derived HIV-SI at week 26, but did not experience any clinically significant changes. HIV-SI in HIV D+/R+ transplant recipients is rare, and the clinical ramifications appear negligible.

The benefits of bilateral lung transplantation (BLT) versus single lung transplantation (SLT) are still debated. One impediment to clinical recommendations is that BLT vs. SLT advantages may vary based on underlying disease. Since both options are clinically tenable in patients with emphysema, we conducted a comprehensive assessment of lung allograft survival in this population. Using U.S. registry data, we studied time to all-cause allograft failure in 8,092 patients 12 years or older transplanted from 2006 to 2022, adjusting for recipient, donor, and transplant factors by inverse propensity weighting. Median allograft survival was 6.6 years in BLT compared to 5.3 years in SLT, a 25% risk-adjusted survival advantage of _0.81.3_1.8 years. Risk-adjusted bilateral survival advantages varied between 0.9 and 2.4 years across eleven subgroups. Median allograft survival in BLT was 1.2 years greater than right SLT and 2.0 years greater than left SLT. During the 16-year study period, allograft survival steadily improved for BLT but not for SLT. Although the 25% BLT survival advantage pre-dated the pandemic, COVID-19 may have contributed to an apparent SLT survival decline. Recognizing the possible influence of residual confounding due to selection biases, these findings may aid offer decision-making when both donor lungs are available.

BACKGROUND:Due to high prevalence of Kaposi Sarcoma (KS)-Associated Herpesvirus (KSHV) among people with HIV, KSHV-associated disease (KAD) may be increased after kidney transplantation from donors with HIV (HIV D+) to recipients with HIV (HIV R+). METHODS:Anti-KSHV antibodies were measured in HIV R+ and donors with and without HIV (HIV D-) using a 30-antigen multiplex assay within three multicenter kidney transplantation studies. KSHV seropositivity was defined as reactivity to conventional KSHV antigens (≥1 ORF73 or K8.1); reactivity to expanded 5-antigen and 30-antigen panels were also reported. Risk factors were identified using modified Poisson regression. Recipients were monitored for post-transplant anti-KSHV antibody changes and KAD. RESULTS:KSHV seroprevalence was 40.6% (143/352) among HIV R+, 25.2% (33/131) among HIV D+, and 7.5% (4/53) among HIV D-. In the multivariable model, only men who have sex with men (MSM) was associated with KSHV seropositivity: relative risk 1.51 (95% confidence interval [CI] 1.07-2.14) in recipients and 2.39 (95%CI 1.03-5.53) in donors. Among 418 HIV R+ (215 HIV D+/R+, 203 HIV D-/R+), there were 5 KAD cases (incidence 0.63 cases/100 person-years, 95%CI 0.26-1.52): 3 skin-only KS, 1 multicentric Castleman disease, 1 allograft KS. The allograft KS occurred in a female HIV D+/R+ and was likely donor-derived. Remaining KAD cases occurred in male HIV D-/R+ and were likely recipient KSHV reactivation or acquisition. CONCLUSIONS:In the United States, KSHV seroprevalence in donors and recipients with HIV was high, particularly among MSM. Reassuringly, KSHV-associated disease was rare, and primarily attributed to recipient rather than donor-derived KSHV.