Faculty Bibliography

OBJECTIVE:End-stage lung disease from severe COVID-19 infection is an increasingly common indication for lung transplantation (LT), but there are limited data on outcomes. We evaluated 1-year COVID-19 LT outcomes. METHODS:We identified all adult US LT recipients January 2020 to October 2022 in the Scientific Registry for Transplant Recipients, using diagnosis codes to identify recipients transplanted for COVID-19. We used multivariable regression to compare in-hospital acute rejection, prolonged ventilator support, tracheostomy, dialysis, and 1-year mortality between COVID-19 and non-COVID-19 recipients, adjusting for donor, recipient, and transplant characteristics. RESULTS:LT for COVID-19 increased from 0.8% to 10.7% of total LT volume during 2020 to 2021. The number of centers performing LT for COVID-19 increased from 12 to 50. Recipients transplanted for COVID-19 were younger; were more likely to be male and Hispanic; were more likely to be on a ventilator, extracorporeal membrane oxygenation support, and dialysis pre-LT; were more likely to receive bilateral LT; and had higher lung allocation score and shorter waitlist time than other recipients (all P values < .001). COVID-19 LT had higher risk of prolonged ventilator support (adjusted odds ratio, 2.28; P < .001), tracheostomy (adjusted odds ratio 5.3; P < .001), and longer length of stay (median, 27 vs 19 days; P < .001). Risk of in-hospital acute rejection (adjusted odds ratio, 0.99; P = .95) and 1-year mortality (adjusted hazard ratio, 0.73; P = .12) were similar for COVID-19 LTs and LTs for other indications, even accounting for center-level differences. CONCLUSIONS:COVID-19 LT is associated with higher risk of immediate postoperative complications but similar risk of 1-year mortality despite more severe pre-LT illness. These encouraging results support the ongoing use of LT for COVID-19-related lung disease.

Kidney transplantation from blood type A2/A2B donors to type B recipients (A2→B) has increased dramatically under the current Kidney Allocation System (KAS). Among living donor transplant recipients, A2-incompatible transplants are associated with an increased risk of all-cause and death-censored graft failure. In light of this, we used SRTR data from 12/2014-6/2022 to evaluate the association between A2→B listing and time to deceased donor kidney transplantation (DDKT) and post-DDKT outcomes for A2→B recipients. Among 53,409 type B waitlist registrants, only 12.6% were listed as eligible to accept A2→B offers ("A2-eligible"). 1-/3-/5-year DDKT rates were 32.1%/61.4%/72.1% among A2-eligible candidates and 14.1%/29.9%/44.1% among A2-ineligible candidates, with the former experiencing a 133% higher rate of DDKT (Cox weighted HR = _2.192.33_2.47; p<0.001). The 7-year adjusted mortality was comparable between A2→B and B-ABOc (type B/O donors to B recipients) recipients (wHR _0.780.94_1.13, p=0.5). Moreover, there was no difference between A2→B vs. B-ABOc DDKT recipients with regards to death-censored graft failure (wHR _0.771.00_1.29, p>0.9) or all-cause graft loss (wHR _0.820.96_1.12, p=0.6). Following its broader adoption since the implementation of KAS, A2→B DDKT appears to be a safe and effective transplant modality for eligible candidates. As such, A2→B listing for eligible type B candidates should be expanded.

BACKGROUND:Kidney transplant (KT) candidates with HIV face higher mortality on the waitlist compared with candidates without HIV. Because the HIV Organ Policy Equity (HOPE) Act has expanded the donor pool to allow donors with HIV (D+), it is crucial to understand whether this has impacted transplant rates for this population. METHODS:Using a linkage between the HOPE in Action trial (NCT03500315) and Scientific Registry of Transplant Recipients, we identified 324 candidates listed for D+ kidneys (HOPE) compared with 46 025 candidates not listed for D+ kidneys (non-HOPE) at the same centers between April 26, 2018, and May 24, 2022. We characterized KT rate, KT type (D+, false-positive [FP; donor with false-positive HIV testing], D- [donor without HIV], living donor [LD]) and quantified the association between HOPE enrollment and KT rate using multivariable Cox regression with center-level clustering; HOPE was a time-varying exposure. RESULTS:HOPE candidates were more likely male individuals (79% versus 62%), Black (73% versus 35%), and publicly insured (71% versus 52%; P < 0.001). Within 4.5 y, 70% of HOPE candidates received a KT (41% D+, 34% D-, 20% FP, 4% LD) versus 43% of non-HOPE candidates (74% D-, 26% LD). Conversely, 22% of HOPE candidates versus 39% of non-HOPE candidates died or were removed from the waitlist. Median KT wait time was 10.3 mo for HOPE versus 60.8 mo for non-HOPE candidates (P < 0.001). After adjustment, HOPE candidates had a 3.30-fold higher KT rate (adjusted hazard ratio = 3.30, 95% confidence interval, 2.14-5.10; P < 0.001). CONCLUSIONS:Listing for D+ kidneys within HOPE trials was associated with a higher KT rate and shorter wait time, supporting the expansion of this practice for candidates with HIV.

BACKGROUND:Cytomegalovirus (CMV)-seronegative lung transplant recipients (LTRs) with seropositive donors (CMV D+/R-) have the highest mortality of all CMV serostatuses. Due to immunosenescence and other factors, we hypothesized CMV D+/R- status might disproportionately impact older LTRs. Thus, we investigated whether recipient age modified the relationship between donor CMV status and mortality among CMV-seronegative LTRs. METHODS:Adult, CMV-seronegative first-time lung-only recipients were identified through the Scientific Registry of Transplant Recipients between May 2005 and December 2019. We used adjusted multivariable Cox regression to assess the relationship of donor CMV status and death. Interaction between recipient age and donor CMV was assessed via likelihood ratio testing of nested Cox models and by the relative excess risk due to interaction (RERI) and attributable proportion (AP) of joint effects. RESULTS:We identified 11,136 CMV-seronegative LTRs. The median age was 59 years; 65.2% were male, with leading transplant indication of idiopathic pulmonary fibrosis (35.6%); and 60.8% were CMV D+/R-. In multivariable modeling, CMV D+/R- status was associated with 27% increased hazard of death (adjusted hazard ratio: 1.27, 95% confidence interval: 1.21-1.34) compared to CMV D-/R-. Recipient age ≥60 years significantly modified the relationship between donor CMV-seropositive status and mortality on the additive scale, including RERI 0.24 and AP 11.4% (p = 0.001), that is, the interaction increased hazard of death by 0.24 and explained 11.4% of mortality in older CMV D+ recipients. CONCLUSIONS:Among CMV-seronegative LTRs, donor CMV-seropositive status confers higher risk of posttransplant mortality, which is amplified in older recipients. Future studies should define optimal strategies for CMV prevention and management in older D+/R- LTRs.

BACKGROUND:Disparities in pediatric kidney transplantation (KT) result in reduced access and worse outcomes for minority children. We assessed the impact of recent systems changes on these disparities. METHODS:This is a retrospective cohort study of pediatric patients utilizing data from the US Renal Data System (n = 7547) and Scientific Registry of Transplant Recipients (n = 6567 waitlisted and n = 6848 transplanted patients). We compared access to transplantation, time to deceased donor kidney transplant (DDKT), and allograft failure (ACGF) in the 5 years preceding implementation of the Kidney Allocation System (KAS) to the 5 years post-KAS implementation 2010-2014 vs. 2015-2019, respectively. RESULTS:p = 0.05) while there was no difference in 3- or 5-year ACGF among LDKT recipients. CONCLUSIONS:After KAS implementation, there is equity in time to DDKT. Pre-KAS increased hazard of ACGF among Black children has decreased in the post-KAS era; however, persistent disparities exist in time to transplant listing among Black and Hispanic children when compared to white children. A higher resolution version of the Graphical abstract is available as Supplementary information.

UNLABELLED:Incompatible living donor kidney transplant recipients (ILDKTr) require desensitization to facilitate transplantation, and this substantial upfront immunosuppression may result in serious complications, including cancer. METHODS/UNASSIGNED:To characterize cancer risk in ILDKTr, we evaluated 858 ILDKTr and 12 239 compatible living donor kidney transplant recipients (CLDKTr) from a multicenter cohort with linkage to the US transplant registry and 33 cancer registries (1997-2016). Cancer incidence was compared using weighted Cox regression. RESULTS/UNASSIGNED:Among ILDKTr, the median follow-up time was 6.7 y (maximum 16.1 y) for invasive cancers (ascertained via cancer registry linkage) and 5.0 y (maximum 16.1 y) for basal and squamous cell carcinomas (ascertained via the transplant registry and censored for transplant center loss to follow-up). Invasive cancers occurred in 53 ILDKTr (6.2%) and 811 CLDKTr (6.6%; weighted hazard ratio [wHR] 1.01; 95% confidence interval [CI], 0.76-1.35). Basal and squamous cell carcinomas occurred in 41 ILDKTr (4.8%) and 737 CLDKTr (6.0%) (wHR 0.99; 95% CI, 0.69-1.40). Cancer risk did not vary according to donor-specific antibody strength, and in an exploratory analysis, was similar between CLDKTr and ILDKTr for most cancer types and according to cancer stage, except ILDKTr had a suggestively increased risk of colorectal cancer (wHR 3.27; 95% CI, 1.23-8.71); however, this elevation was not significant after correction for multiple comparisons. CONCLUSIONS/UNASSIGNED:These findings indicate that the risk of cancer is not increased for ILDKTr compared with CLDKTr. The possible elevation in colorectal cancer risk is unexplained and might suggest a need for tailored screening or prevention.

Decreased postdonation eGFR is associated with a higher risk of ESRD after living kidney donation, even when accounting for predonation characteristics. The Toulouse-Rangueil model (TRM) estimates 12 month postdonation eGFR (eGFR12) to inform counseling of candidates for living donation. The TRM was validated in several single-center European cohorts but has not been validated in US donors. We assessed the TRM in living kidney donors in the US using SRTR data 1/2000-6/2021. We compared the 2021 CKD-EPI equation eGFR12 observed estimates to the TRM eGFR12 predictions. Median (IQR) bias was -3.4 (-9.3, 3.4) mL/min/1.73 m². Bias was higher for males vs. females (bias [IQR] -4.4 [-9.9, 1.8] vs. -2.9 [-8.8, 4.1]) and younger (31-40) vs. older donors (>50) (bias -4.9 [-10.6, 3.0] vs. -2.1 [-7.5, 4.0]). Bias was also larger for Black vs. White donors (bias (-6.7 [-12.1, -0.3], p < 0.001) vs. (-3.4 [-9.1, 3.1], p < 0.001)). Overall correlation was 0.71. In a sensitivity analysis using the 2009 CKD-EPI equation, results were generally consistent with exception to a higher overall bias (bias -4.2 [-9.8, 2.4]). The TRM overestimates postdonation renal function among US donors. Overestimation was greatest for those at higher risk for postdonation ESRD including male, Black, and younger donors. A new equation is needed to estimate postdonation renal function.

Older compatible living donor kidney transplant (CLDKT) recipients have higher mortality and death-censored graft failure (DCGF) compared to younger recipients. These risks may be amplified in older incompatible living donor kidney transplant (ILDKT) recipients who undergo desensitization and intense immunosuppression. In a 25-center cohort of ILDKT recipients transplanted between September 24, 1997, and December 15, 2016, we compared mortality, DCGF, delayed graft function (DGF), acute rejection (AR), and length of stay (LOS) between 234 older (age ≥60 years) and 1172 younger (age 18-59 years) recipients. To investigate whether the impact of age was different for ILDKT recipients compared to 17 542 CLDKT recipients, we used an interaction term to determine whether the relationship between posttransplant outcomes and transplant type (ILDKT vs CLDKT) was modified by age. Overall, older recipients had higher mortality (hazard ratio: _1.632.07_2.65, P < .001), lower DCGF (hazard ratio: _0.360.53_0.77, P = .001), and AR (odds ratio: _0.390.54_0.74, P < .001), and similar DGF (odds ratio: _0.461.03_2.33, P = .9) and LOS (incidence rate ratio: _0.880.98_1.10, P = 0.8) compared to younger recipients. The impact of age on mortality (interaction P = .052), DCGF (interaction P = .7), AR interaction P = .2), DGF (interaction P = .9), and LOS (interaction P = .5) were similar in ILDKT and CLDKT recipients. Age alone should not preclude eligibility for ILDKT.

BACKGROUND:In the context of the organ shortage, donation after circulatory death (DCD) provides an opportunity to expand the donor pool. Although deceased-donor liver transplantation from DCD donors has expanded, DCD livers continue to be discarded at elevated rates; the use of DCD livers from older donors, or donors with comorbidities, is controversial. METHODS:Using US registry data from 2009 to 2020, we identified 1564 candidates on whose behalf a DCD liver offer was accepted ("acceptors") and 16 981 candidates on whose behalf the same DCD offers were declined ("decliners"). We characterized outcomes of decliners using a competing risk framework and estimated the survival benefit (adjusted hazard ratio [95% confidence interval]) of accepting DCD livers using Cox regression. RESULTS:Within 10 y of DCD offer decline, 50.9% of candidates died or were removed from the waitlist before transplantation with any type of allograft. DCD acceptors had lower mortality compared with decliners at 10 y postoffer (35.4% versus 48.9%, P < 0.001). After adjustment for candidate covariates, DCD offer acceptance was associated with a 46% reduction in mortality (0.54 [0.49-0.61]). Acceptors of older (age ≥50), obese (body mass index ≥30), hypertensive, nonlocal, diabetic, and increased risk DCD livers had 44% (0.56 [0.42-0.73]), 40% (0.60 [0.49-0.74]), 48% (0.52 [0.41-0.66]), 46% (0.54 [0.45-0.65]), 32% (0.68 [0.43-1.05]), and 45% (0.55 [0.42-0.72]) lower mortality risk compared with DCD decliners, respectively. CONCLUSIONS:DCD offer acceptance is associated with considerable long-term survival benefits for liver transplant candidates, even with older DCD donors or donors with comorbidities. Increased recovery and utilization of DCD livers should be encouraged.