Faculty Bibliography

Nondirected kidney donors can initiate living donor chains that end to patients on the waitlist. We compared 749 National Kidney Registry (NKR) waitlist chain end transplants to other transplants from the NKR and the Scientific Registry of Transplant Recipients between February 2008 and September 2020. Compared to other NKR recipients, chain end recipients were more often older (53 vs. 52 years), black (32% vs. 15%), publicly insured (71% vs. 46%), and spent longer on dialysis (3.0 vs. 1.0 years). Similar differences were noted between chain end recipients and non-NKR living donor recipients. Black patients received chain end kidneys at a rate approaching that of deceased donor kidneys (32% vs. 34%). Chain end donors were older (52 vs. 44 years) with slightly lower glomerular filtration rates (93 vs. 98 ml/min/1.73 m² ) than other NKR donors. Chain end recipients had elevated risk of graft failure and mortality compared to control living donor recipients (both p < .01) but lower graft failure (p = .03) and mortality (p < .001) compared to deceased donor recipients. Sharing nondirected donors among a multicenter network may improve the diversity of waitlist patients who benefit from living donation.

Background/UNASSIGNED:COVID-19-associated mucormycosis (CAM) is a recently emerging entity. There is a lack of reports of CAM in organ transplant recipients. Methods/UNASSIGNED:We conducted a multicenter (n = 18) retrospective research in India during November 2020 to July 2021. The purpose of this study was to explore the clinical spectrum, outcome and risk factors for mortality of CAM in kidney transplant recipients (KTRs). Results/UNASSIGNED:= 0.05] was associated with mortality. The median follow-up of the study was 60 (35-60) d. Conclusions/UNASSIGNED:We describe the largest case series of CAM in KTRs. Morality in pulmonary CAM is extremely high. Severe COVID-19 pose extra risk for the development of CAM and associated mortality. Our report will help in better understanding the conundrum and management of CAM.

BACKGROUND AND AIMS/OBJECTIVE:Frailty is a well-established risk factor for poor outcomes in patients with cirrhosis awaiting liver transplantation (LT), but whether it predicts outcomes among those who have undergone LT is unknown. APPROACH AND RESULTS/UNASSIGNED:Adult LT recipients from 8 US centers (2012-2019) were included. Pre-LT frailty was assessed in the ambulatory setting using the Liver Frailty Index (LFI). "Frail" was defined by an optimal cut point of LFI ≥ 4.5. We used the 75th percentile to define "prolonged" post-LT length of stay (LOS; ≥12 days), intensive care unit (ICU) days (≥4 days), and inpatient days within 90 post-LT days (≥17 days). Of 1166 LT recipients, 21% were frail pre-LT. Cumulative incidence of death at 1 and 5 years was 6% and 16% for frail and 4% and 10% for nonfrail patients (overall log-rank p = 0.02). Pre-LT frailty was associated with an unadjusted 62% increased risk of post-LT mortality (95% CI, 1.08-2.44); after adjustment for body mass index, HCC, donor age, and donation after cardiac death status, the HR was 2.13 (95% CI, 1.39-3.26). Patients who were frail versus nonfrail experienced a higher adjusted odds of prolonged LT LOS (OR, 2.00; 95% CI, 1.47-2.73), ICU stay (OR, 1.56; 95% CI, 1.12-2.14), inpatient days within 90 post-LT days (OR, 1.72; 95% CI, 1.25-2.37), and nonhome discharge (OR, 2.50; 95% CI, 1.58-3.97). CONCLUSIONS:Compared with nonfrail patients, frail LT recipients had a higher risk of post-LT death and greater post-LT health care utilization, although overall post-LT survival was acceptable. These data lay the foundation to investigate whether targeting pre-LT frailty will improve post-LT outcomes and reduce resource utilization.

BACKGROUND:Historically, donation after circulatory death (DCD) livers were frequently discarded due to higher mortality and graft loss after liver transplantation (LT). However, the demand for liver transplantation continues to outstrip the supply of "acceptable" organs. Additionally, changes in the donor pool, organ allocation, clinical management of donors and recipients, and improved clinical protocols might have altered post-DCD-LT outcomes. METHODS:We studied 5,975 recovered DCD livers using U.S. SRTR data from 2005-2017, with a comparison group of 78,235 adult DBD livers recovered during the same time period. We quantified temporal trends in discard using adjusted multilevel logistic regression and temporal trends in post-LT mortality and graft loss for DCD LT recipients using adjusted Cox regression. RESULTS:DCD livers were more likely to be discarded than DBD livers across the entire study period, and the relative likelihood of discard increased over time (adjusted odds ratio [aOR] of discard DCD vs. DBD 3.854.455.14 2005-2007, 5.225.876.59 2015-2017) despite improving outcomes after DCD LT. Mortality risk for DCD LTs decreased in each time period (compared to 2005-2007, aHR 2008-2011 0.720.840.97, aHR 2012-2014 0.480.580.70, aHR 2015-2017 0.340.430.55), as did risk of graft loss (compared to 2005-2007, aHR 2008-2011 0.690.810.94, aHR 2012-2014 0.450.550.67, aHR 2015-2017 0.360.450.56). CONCLUSIONS:Despite dramatic improvements in outcomes of DCD LT recipients, DCD livers remain substantially more likely to be discarded than DBD livers, and this discrepancy has actually increased over time. DCD livers are underutilized and have the potential to expand the donor pool.

Kidney transplantation (KT) experts did not support the use of subjective unintentional weight loss to measure shrinking in the physical frailty phenotype (PFP); a clinically feasible and predictive measure of shrinking is needed. To test whether unintentional weight loss could be replaced by an assessment of sarcopenia using existing CT scans, we performed a prospective cohort study of adult KT recipients with original PFP (oPFP) measured at admission (December 2008-February 2020). We ascertained sarcopenia by calculating skeletal muscle index from available, clinically obtained CTs within 1-year pre-KT (male < 50 cm² /m² ; female < 39 cm² /m² ) and combined it with the original four components to determine new PFP (nPFP) scores. Frailty was classified by frailty score: 0: non-frail; 1-2: pre-frail; ≥3: frail. Mortality and graft loss hazard ratios (HRs) were estimated using adjusted Cox proportional hazard models. Model discrimination was quantified using Harrell's C-statistic. Among 1113 recipients, 18.6% and 17.1% were frail by oPFP and nPFP, respectively. Compared to non-frail recipients, frail patients by either PFP had higher risks of mortality (oPFP HR = 1.67, 95% CI: 1.07-2.62, C = 0.710; nPFP HR = 1.68, 95% CI: 1.06-2.66, C = 0.710) and graft loss (oPFP HR = 1.67, 95% CI: 1.17-2.40, C = 0.631; nPFP HR = 1.66, 95% CI: 1.15-2.40, C = 0.634) with similar discriminations. oPFP and nPFP are equally useful in risk prediction for KT recipients; oPFP may aid in screening patients for pre-KT interventions, while nPFP may assist in nuanced clinical decision-making.

Rationale & Objective/UNASSIGNED:Posttransplant diabetes mellitus (DM) after kidney transplantation increases morbidity and mortality, particularly in older and obese recipients. We aimed to examine the impact of immunosuppression selection on the risk of posttransplant DM among both older and obese kidney transplant recipients. Study Design/UNASSIGNED:Retrospective database study. Setting & Participants/UNASSIGNED:Kidney-only transplant recipients aged ≥18 years from 2005 to 2016 in the United States from US Renal Data System records, which integrate Organ Procurement and Transplantation Network/United Network for Organ Sharing records with Medicare billing claims. Exposures/UNASSIGNED:Various immunosuppression regimens in the first 3 months after transplant. Outcomes/UNASSIGNED:Development of DM >3 months-to-1 year posttransplant. Analytical Approach/UNASSIGNED:We used multivariable Cox regression to compare the incidence of posttransplant DM by immunosuppression regimen with the reference regimen of thymoglobulin (TMG) or alemtuzumab (ALEM) with tacrolimus + mycophenolic acid + prednisone using inverse propensity weighting. Results/UNASSIGNED:(aHR, 0.63; 95% CI, 0.46-0.87). Limitations/UNASSIGNED:Retrospective study and lacked data on immunosuppression levels. Conclusions/UNASSIGNED:The beneficial impact of steroid avoidance using tacrolimus on posttransplant DM appears to differ by patient age and induction regimen.

Vaccine-induced SARS-CoV-2 antibody responses are attenuated in solid organ transplant recipients (SOTRs) and breakthrough infections are more common. Additional SARS-CoV-2 vaccine doses increase anti-spike IgG in some SOTRs, but it is uncertain whether neutralization of variants of concern (VOCs) is enhanced. We tested 47 SOTRs for clinical and research anti-spike IgG, pseudoneutralization (ACE2 blocking), and live-virus neutralization (nAb) against VOCs before and after a third SARS-CoV-2 vaccine dose (70% mRNA, 30% Ad26.COV2.S) with comparison to 15 healthy controls after two mRNA vaccine doses. We used correlation analysis to compare anti-spike IgG assays and focused on thresholds associated with neutralization. A third SARS-CoV-2 vaccine dose increased median total anti-spike (1.6-fold), pseudoneutralization against VOCs (2.5-fold vs. Delta), and neutralizing antibodies (1.4-fold against Delta). However, neutralization activity was significantly lower than healthy controls (p < .001); 32% of SOTRs had zero detectable nAb against Delta after third vaccination compared to 100% for controls. Correlation with nAb was seen at anti-spike IgG >4 Log₁₀ (AU/ml) on the Euroimmun ELISA and >4 Log₁₀ (AU/ml) on the MSD research assay. These findings highlight benefits of a third vaccine dose for some SOTRs and the need for alternative strategies to improve protection in a significant subset of this population.

Liver transplantation (LT) from donors-with-HIV to recipients-with-HIV (HIV D+/R+) is permitted under the HOPE Act. There are only three international single-case reports of HIV D+/R+ LT, each with limited follow-up. We performed a prospective multicenter pilot study comparing HIV D+/R+ to donors-without-HIV to recipients-with-HIV (HIV D-/R+) LT. We quantified patient survival, graft survival, rejection, serious adverse events (SAEs), human immunodeficiency virus (HIV) breakthrough, infections, and malignancies, using Cox and negative binomial regression with inverse probability of treatment weighting. Between March 2016-July 2019, there were 45 LTs (8 simultaneous liver-kidney) at 9 centers: 24 HIV D+/R+, 21 HIV D-/R+ (10 D- were false-positive). The median follow-up time was 23 months. Median recipient CD4 was 287 cells/µL with 100% on antiretroviral therapy; 56% were hepatitis C virus (HCV)-seropositive, 13% HCV-viremic. Weighted 1-year survival was 83.3% versus 100.0% in D+ versus D- groups (p = .04). There were no differences in one-year graft survival (96.0% vs. 100.0%), rejection (10.8% vs. 18.2%), HIV breakthrough (8% vs. 10%), or SAEs (all p > .05). HIV D+/R+ had more opportunistic infections, infectious hospitalizations, and cancer. In this multicenter pilot study of HIV D+/R+ LT, patient and graft survival were better than historical cohorts, however, a potential increase in infections and cancer merits further investigation.

BACKGROUND:Frailty, a phenotype characterized by decreased physiologic reserve and the inability to recover following confrontation with a stressor like hemodialysis, may help identify which patients on incident hemodialysis will experience longer postdialysis recovery times. Recovery time is associated with downstream outcomes, including quality of life and mortality. We characterized postdialysis recovery times among patients new to hemodialysis and quantified the association between frailty and hemodialysis recovery time. METHODS:Among 285 patients on hemodialysis enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease (PACE) study, frailty was measured using the Fried phenotype. Self-reported recovery time was obtained by telephone interview. We estimated the association of frailty (intermediately frail and frail versus nonfrail) and postdialysis recovery time using adjusted negative binomial regression. RESULTS:Median time between dialysis initiation and study enrollment was 3.4 months (IQR, 2.7-4.9), and that between initiation and recovery time assessment was 11 months (IQR, 9.3-15). Mean age was 55 years, 24% were >65 years, and 73% were Black; 72% of individuals recovered in ≤1 hour, 20% recovered in 1-6 hours, 5% required 6-12 hours to recover, and <5% required >12 hours to recover. Those with intermediate frailty, frailty, and age ≤65 years had 2.56-fold (95% CI, 1.45 to 4.52), 1.72-fold (95% CI, 1.03 to 2.89), and 2.35-fold (95% CI, 1.44 to 3.85) risks, respectively, of longer recovery time independent of demographic characteristics, comorbidity, and dialysis-related factors. CONCLUSIONS:In adults new to hemodialysis, frailty was independently associated with prolonged postdialysis recovery. Future studies should assess the effect of frailty-targeted interventions on recovery time to improve clinical outcomes.