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SHELTER is a trial of transplanting lungs from deceased donors with hepatitis C virus (HCV) infection into HCV-negative candidates (sponsor: Merck; NCT03724149). Few trials have reported outcomes using thoracic organs from HCV-RNA+ donors and none have reported quality of life (QOL). Methods: This study is a single-arm trial of 10 lung transplants at a single center. Patients were included who were between 18 and 67 y of age and waitlisted for lung-only transplant. Patients were excluded who had evidence of liver disease. Primary outcome was HCV cure (sustained virologic response 12 wk after completing antiviral therapy). Recipients longitudinally reported QOL using the validated RAND-36 instrument. We also applied advanced methods to match HCV-RNA+ lung recipients to HCV-negative lung recipients in a 1:3 ratio at the same center. Results: Between November 2018 and November 2020, 18 patients were consented and opted-in for HCV-RNA+ lung offers in the allocation system. After a median of 37 d (interquartile range [IQR], 6-373) from opt-in, 10 participants received double lung transplants. The median recipient age was 57 y (IQR, 44-67), and 7 recipients (70%) had chronic obstructive pulmonary disease. The median lung allocation score at transplant was 34.3 (IQR, 32.7-86.9). Posttransplant, 5 recipients developed primary graft dysfunction grade 3 on day 2 or 3, although none required extracorporeal membrane oxygenation. Nine patients received elbasvir/grazoprevir, whereas 1 patient received sofosbuvir/velpatasvir. All 10 patients were cured of HCV and survived to 1 y (versus 83% 1-y survival among matched comparators). No serious adverse events were found to be related to HCV or treatment. RAND-36 scores showed substantial improvement in physical QOL and some improvement in mental QOL. We also examined forced expiratory volume in 1 s-the most important lung function parameter after transplantation. We detected no clinically important differences in forced expiratory volume in 1 s between the HCV-RNA+ lung recipients versus matched comparators. Conclusions: SHELTER adds important evidence regarding the safety of transplanting HCV-RNA+ lungs into uninfected recipients and suggests QOL benefits.
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Background: Historically, many organs from deceased donors with hepatitis C virus (HCV) were discarded. The advent of highly curative direct-acting antiviral (DAA) therapies motivated transplant centers to conduct trials of transplanting HCV-viremic organs (nucleic acid amplification test positive) into HCV-negative recipients, followed by DAA treatment. However, the factors that influence candidates' decisions regarding acceptance of transplant with HCV-viremic organs are not well understood. Methods: To explore patient-level perceptions, influences, and experiences that inform candidate decision-making regarding transplant with organs from HCV-viremic donors, we conducted a qualitative semistructured interview study embedded within 3 clinical trials investigating the safety and efficacy of transplanting lungs and kidneys from HCV-viremic donors into HCV-negative recipients. The study was conducted from June 2019 to March 2021. Results: Among 44 HCV-negative patients listed for organ transplant who were approached for enrollment in the applicable clinical trial, 3 approaches to decision-making emerged: positivist, risk analyses, and instinctual response. Perceptions of risk contributed to conceptualizations of factors influencing decisions. Moreover, most participants relied on multiple decision-making approaches, either simultaneously or sequentially. Conclusions: Understanding how different decisional models influence patients' choices regarding transplant with organs from HCV-viremic donors may promote shared decision-making among transplant patients and providers.
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OBJECTIVE: The aim of this study was to determine graft function and survival for kidney transplants from deceased donors with acute kidney injury (AKI) that persists at the time of organ procurement. BACKGROUND: Kidneys from donors with AKI are often discarded and may provide an opportunity to selectively expand the donor pool. METHODS: Using Organ Procurement and Transplantation Network and DonorNet data, we studied adult kidney-only recipients between May 1, 2007 and December 31, 2016. DonorNet was used to characterize longitudinal creatinine trends and urine output. Donor AKI was defined using KDIGO guidelines and terminal creatinine ≥1.5 mg/dL. We compared outcomes between AKI kidneys versus "ideal comparator" kidneys from donors with no or resolved AKI stage 1 plus terminal creatinine <1.5mg/dL. We fit proportional hazards models and hierarchical linear regression models for the primary outcomes of all-cause graft failure (ACGF) and 12-month estimated glomerular filtration rate (eGFR), respectively. RESULTS: We identified 7660 donors with persistent AKI (33.2% with AKI stage 3) from whom ≥1 kidney was transplanted. Observed rates of ACGF within 3 years were similar between recipient groups (15.5% in AKI vs 15.1% ideal comparator allografts, P = 0.2). After risk adjustment, ACGF was slightly higher among recipients of AKI kidneys (adjusted hazard ratio 1.05, 95% confidence interval: 1.01-1.09). The mean 12-month eGFR for AKI kidney recipients was lower, but differences were not clinically important (56.6 vs 57.5 mL/min/1.73m 2 for ideal comparator kidneys; P < 0.001). There were 2888 kidneys discarded from donors with AKI, age ≤65 years, without hypertension or diabetes, and terminal creatinine ≤4 mg/dL. CONCLUSION: Kidney allografts from donors with persistent AKI are often discarded, yet those that were transplanted did not have clinically meaningful differences in graft survival and function.
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Lesión Renal Aguda , Trasplante de Riñón , Adulto , Humanos , Anciano , Creatinina , Estudios de Cohortes , Donantes de Tejidos , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología , Supervivencia de Injerto , Riñón , Almacenamiento y Recuperación de la Información , Estudios RetrospectivosRESUMEN
RATIONALE & OBJECTIVE: A robust relationship between procedure volume and clinical outcomes has been demonstrated across many surgical fields. This study assessed whether a center volume-outcome relationship exists for contemporary kidney transplantation, specifically for diabetic recipients, older recipients (aged ≥65 years), and recipients of high kidney donor profile index (KDPI ≥ 85) kidneys. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adult kidney-only transplant recipients who underwent transplantation between 2009 and 2013 (N = 79,581). EXPOSURES: The primary exposure variable was center volume, categorized into quartiles based on the total kidney transplantation volume. Quartile 1 (Q1) centers performed a mean of fewer than 66 kidney transplantations per year, whereas Q4 centers performed a mean of more than 196 kidney transplantations per year. OUTCOMES: All-cause graft failure and mortality within 3 years of transplantation. ANALYTICAL APPROACH: Multivariable Cox frailty models were used to adjust for donor characteristics, recipient characteristics, and cold ischemia time. RESULTS: Minor differences in rates of 3-year deceased donor all-cause graft failure across quartiles of center volume were observed (14.9% for Q1 vs 16.7% for Q4), including in subgroups (diabetic recipients, 18.4% for Q1 vs 19.7% for Q4; older recipients, 19.4% for Q1 vs 22.5% for Q4; recipients of high KDPI kidneys, 26.5% for Q1 vs 26.5% for Q4). Results were similar for 3-year mortality. After adjustment for donor, recipient, and graft characteristics using Cox regression, center volume was not significantly associated with all-cause graft failure or mortality within 3 years, except that diabetic recipients at Q3 centers had slightly lower mortality (compared with Q1 centers, adjusted HR of 0.85 [95% CI, 0.73-0.99]). LIMITATIONS: Potential unmeasured confounding from patient comorbid conditions and organ selection. CONCLUSIONS: These findings provide little evidence that care in higher volume centers is associated with better adjusted outcomes for kidney transplant recipients, even in populations anticipated to be at increased risk for graft failure or death.