Transplantation Direct最新文献

Background: Donation after circulatory death liver transplantation (DCD LT) is underused given historical outcomes fraught with ischemic cholangiopathy (IC). We aimed to assess 6-mo IC in LT from DCD via normothermic regional perfusion (NRP) compared with DCD via static cold storage (SCS).

Methods: A retrospective review of adult Maastricht-III DCD liver donors and recipients at the University of Colorado Hospital from January 1, 2017, to August 27, 2024, was performed. The 6-mo IC rate was compared between NRP and SCS. Secondary outcomes included biochemical assessments of accepted versus declined NRP liver allografts and allograft and patient survival for NRP and SCS groups.

Results: One hundred sixty-two DCD LTs (SCS = 79; NRP = 97) were performed and 150 recipients (SCS = 74; NRP = 86) reached 6-mo follow-up. Six-month IC was lower for NRP compared with SCS (1.2% versus 9.5%, P = 0.03). The Donor Risk Index (2.44 [2.02-2.82] versus 2.17 [1.97-2.30], P = 0.002) and UK DCD Risk Score (4.2 ± 2.9 versus 3.2 ± 2.3, P = 0.008) were higher for NRP versus SCS. The Liver Graft assessment Following Transplantation score was less for NRP compared with SCS (-3.3 versus -3.1, P < 0.05). There were several differences in median biochemical parameters during NRP between accepted and declined livers, including higher terminal biliary bicarbonate (22.7 [20.9-29.1] versus 10.8 [7.6-13.1] mEq/L, P = 0.004). There were no significant differences in 12-mo allograft or patient survival for NRP versus SCS.

Conclusions: NRP is a disruptive innovation that improves the utilization of DCD livers. Despite higher-risk donor-recipient pairing for NRP compared with SCS, we demonstrate a decrease in IC for NRP. These data facilitate benchmarking of thoracoabdominal NRP DCD LT and support further protocol development.

Background: The increasing demand for organs has pushed transplant providers to expand kidney acceptance criteria. The use of kidneys from donors with AKI has been shown to provide good long-term graft survival. We aim to evaluate and compare the outcomes of deceased donor kidney transplantation from donors with acute kidney injury (AKI), either with or without renal replacement therapy (AKI-RRT) before donation.

Methods: A single-center retrospective review of all patients who underwent deceased donor kidney transplantation from AKI donors between 2009 and 2020 was performed. AKI donors were defined on the basis of donor terminal creatinine ≥2.0 mg/dL or use of RRT before donation. We compared the outcomes of recipients receiving a kidney from a donor with AKI versus AKI-RRT. Data are presented as medians (interquartile ranges) and numbers (percentages).

Results: Four hundred ninety-six patients were identified, of whom 300 (60.4%) were men with a median age of 57 y at transplantation. Thirty-nine patients received an AKI-RRT, whereas 457 received an AKI kidney. Donors in the AKI-RRT group were younger (28 versus 40), had less incidence of hypertension (15.3% versus 31.9%), and were more likely to be imported (94.9% versus 76.8%). There was a higher incidence of delayed graft function (72% versus 44%, P < 0.001) in the AKI-RRT group. Recipients in both groups had similar 90-d (100% versus 95.2%) and 1-y (100% versus 91.9%) graft survival. With a median follow-up of 5 y, there was no difference in death-censored graft survival in both groups (P = 0.83).

Conclusions: Careful selection of kidneys from donors with AKI on RRT can be safely used for kidney transplantation with favorable clinical outcomes.

Background: As the burden of chronic liver disease and the demand for liver transplants (LT) grows, understanding the interplay between access to care and patient outcomes is increasingly important. In this study, we explored patient characteristics and transplant outcomes in patients undergoing LT evaluations, with a focus on identifying risk factors for expedited LT evaluation.

Methods: This single-center retrospective cohort study included patients who underwent LT evaluation for deceased donor LT between October 2017 and July 2021. Patients were categorized by context: expedited (inpatient) and routine (outpatient) LT evaluation groups. The outcome measures included waitlist status, pre-LT mortality, and post-LT complications.

Results: Of 602 patients, 26% underwent expedited LT evaluation. Patients who underwent expedited evaluation were more likely to have a history of ascites (P < 0.001), hepatic encephalopathy (P < 0.001), and spontaneous bacterial peritonitis (P < 0.001) and had a higher model for end-stage liver disease sodium scores (P < 0.001). Both mortality (35% versus 17%, P < 0.001) and LT (39% versus 22%, P < 0.001) were more common in the expedited group; post-LT mortality was similar up to 2 y. Perceived financial concerns and social security disability income were risk factors for expedited LT evaluation. In addition, greater proximity to the LT center (95% confidence interval, 1.1-6.3; P = 0.025) and speaking a primary language other than English (95% confidence interval, 1.0-10.7; P = 0.042) were risk factors for expedited LT evaluation in women but not in men.

Conclusions: Expedited LT evaluations were associated with more severe illness and higher pre-LT mortality; however, post-LT outcomes were comparable with those of routine evaluations. Identifying psychosocial risk factors may enhance equity and access to LT evaluations, particularly for women who face unique challenges in this context.

Background: In 2020, liver allocation policy in the United States was changed to allow for broader organ sharing, which was hypothesized to reduce patient incentives to travel for transplant. Our objective was to describe patterns of travel for domestic liver transplant pre- and post-acuity circle (AC) implementation.

Methods: Incident adult liver transplant listings between August 16, 2016, and February 3, 2020 (pre-AC) or June 13, 2020, and December 3, 2023 (post-AC) were obtained from the Scientific Registry of Transplant Recipients. We used previously defined geographic catchment areas to classify patients as (1) no travel, (2) travel to a neighboring region, and (3) travel beyond a neighboring region. We used multinomial logistic regression to identify characteristics associated with travel and cause-specific hazards modeling to estimate the association between travel and time to deceased donor transplant, stratified by model for end-stage liver disease (MELD) score and AC era.

Results: Among 83 033 liver candidates, 76% were listed in their home region. Black race, lower educational attainment, increased neighborhood social deprivation, and Medicaid were significantly associated with decreased odds of traveling beyond a neighboring region. After AC, traveling beyond a neighboring region was associated with an increased hazard of transplant for patients with a MELD score <15 (cause-specific hazard ratio [csHR]: 1.25; 95% confidence interval [CI], 1.11-1.40), MELD score 15-24 (csHR: 1.19; 95% CI, 1.07-1.31), and MELD score 25-34 (csHR: 1.15; 95% CI, 1.01-1.32).

Conclusions: Travel frequency, geographic patterns of travel, and characteristics associated with travel were largely unchanged after AC. Changes to allocation policy alone may not equalize patient means or desire to travel for transplant care.

Background: Aortoiliac screening before kidney transplantation is suggested by some guidelines to select patients for transplantation and to assist surgical planning. We investigated the clinical outcomes of systematic screening for aortoiliac disease in potential kidney transplant candidates.

Methods: In this observational study, 470 potential kidney transplant candidates underwent aortoiliac computed tomography angiography. Patients were characterized by the presence of peripheral artery disease and calcification of iliac arteries and aortoiliac arteries. The risk of graft loss and graft function at 1 y posttransplant were examined and clinical decisions based on the vascular findings were assessed.

Results: Clinically diagnosed peripheral artery disease was present in 66 patients (14%), circular calcifications in 101 patients (21%), and aortoiliac stenosis in 77 patients (16%). In 326 patients undergoing kidney transplantation, circular calcification or aortoiliac stenosis was not associated with an increased risk of graft loss (P = 0.45 and P = 0.28) or estimated glomerular filtration rate (P = 0.23 and P = 0.76) at 1 y posttransplant. When evaluated for transplantability, clinical decision-making based on vascular findings was recorded in 67 of 429 patients (16%), including rejection for transplantation in 7 patients (2%) and laterality for surgical implantation in 52 patients (12%).

Conclusions: Systematic screening by aortoiliac computed tomography angiography may assist in surgical planning but seems of limited clinical value in assessing the risk of future graft loss and graft function in patients undergoing kidney transplantation.

Background: The limitations of conventional measures of socioeconomic status (SES) limit our ability to elucidate the role of SES as a key element of social determinants of health in kidney transplantation. This study's objective was to use an innovative SES measure, the HOUsing-based SES measure (HOUSES) index, to examine the effects of social determinants of health on access to and outcomes of kidney transplantation.

Methods: Our study included residents of Minnesota (age older than 18 y) who underwent kidney transplantation at a single center between 2010 and 2020. SES was determined using the HOUSES index, categorized into quartiles (Q1 for lower, Q2-Q4 for higher SES). We used mixed-effects multivariable logistic and Cox models to examine the effects of HOUSES on preemptive transplants, pretransplant dialysis duration, and death-censored graft loss, adjusting for covariates.

Results: Among 1975 eligible patients, 29.4% received preemptive transplants, 34.9% underwent pretransplant dialysis for >3 y, and 15.1% experienced death-censored graft loss for a median follow-up of 7.15 (interquartile range, 4.25-11.38) y. Lower SES recipients (Q1) demonstrated decreased preemptive transplant likelihood (adjusted odds ratio [aOR]: 0.74; 95% confidence interval [CI], 0.57-0.97; P = 0.03), longer dialysis duration (>3 y; aOR: 1.43; 95% CI, 1.01-2.03; P = 0.046), and higher death-censored graft loss (adjusted hazard ratio 1.36; 95% CI, 1.02-1.12; P = 0.036) versus higher SES recipients (Q2-Q4).

Conclusions: We observed significant socioeconomic disparities in kidney transplant access, dialysis duration, and graft survival. The HOUSES index may be a promising tool for individual-based targeted interventions as it identifies SES on an individual rather than an area-level basis.

Background: Deceased donor multiorgan transplants utilizing kidneys (MOTs) can improve outcomes for multiorgan recipients but reduces kidneys for chronic renal failure patients.

Methods: We reviewed the Organ Procurement and Transplantation Network database from 2015 through 2019, for adult deceased donor kidney transplants. Recipients were classified as kidney transplant alone (KTA) (n = 62,252) or MOTs pancreas-kidney, simultaneous pancreas-kidney (n = 3,976), liver-kidney, simultaneous liver-kidney (n = 3,212), heart-kidney, simultaneous heart-kidney (n = 808), and "other"-kidney, simultaneous "other" kidney (n = 73).

Results: Liver, heart, and lung-alone transplants were at least 7 times more frequent than their MOT correlate, whereas the inverse was true with pancreas transplantation with SPKs being by far the most common pancreas transplant type. On average, KTA recipients waited between 2.8 and 21.4 times longer than MOTs, with SPKs waiting the longest of the MOT types. Predialysis initiation transplants were less frequent in KTAs compared with MOTs. Use of high-quality grafts according to Kidney Donor Profile Index < 35% was frequent among MOTs, but uncommon in KTAs who had an Estimated Post Transplant Survival score (EPTS) of >20%. For recipients older than 65, SPKs and SOKs were rare, but SLKs and SHKs had a higher fraction of recipients than KTAs and were much more likely to use a Kidney Donor Profile Index <35% kidney. SPKs and KTAs with an EPTS ≤20% had the best kidney graft survival. KTAs with an EPTS ≤80% had better kidney graft survival than SLKs, SHKs, and SOKs.

Conclusions: This study highlights disparities in access to deceased donor kidneys for kidney-alone candidates versus MOTs and suggests opportunities to improve allocation.

Background: Perioperative intravenous fluids are administered to kidney transplant recipients to maintain hemodynamic stability and graft perfusion; however, the ideal fluid remains uncertain. Although 0.9% saline (saline) is commonly used, its high chloride content causes hyperchloremic metabolic acidosis and may increase the risks of delayed graft function (DGF) and hyperkalemia. Balanced electrolyte solutions (BES) have a more physiological chloride concentration and may reduce these risks. Previous meta-analyses found insufficient evidence to compare BES with saline for these outcomes; however, new studies have recently been published. In this updated review, we compared the effects of BES with saline on the risk of DGF and hyperkalemia in kidney transplantation.

Methods: MEDLINE, Embase, and CENTRAL were searched for randomized controlled trials comparing BES with saline in kidney transplantation. The primary outcomes were DGF and hyperkalemia. Eligible studies were assessed for risk of bias and data were pooled for analysis. The Grading of Recommendations Assessment, Development, and Evaluation framework was used to assess the quality of evidence.

Results: Ten studies involving 1532 participants were included. The quality of evidence was high for deceased donor transplantation and very low for living donor transplantation. The relative risk (RR) of DGF associated with BES compared with saline was 0.83 (95% confidence interval [CI], 0.71-0.96; P = 0.01) in deceased donor transplantation. There was no difference in DGF in living donor transplantation (RR 0.79; 95% CI, 0.26-2.41; P = 0.68). There was no difference in hyperkalemia between groups (RR 0.87; 95% CI, 0.59-1.27; P = 0.46).

Conclusions: Compared with saline, BES reduces the risk of DGF in deceased donor kidney transplantation without increasing hyperkalemia.

Background: Presensitized patients with circulating donor-specific antibodies (DSAs) before transplantation are at risk for antibody-mediated rejection (AMR). Peritransplant desensitization mitigates but does not eliminate the alloimmune response. We examined the possibility that subthreshold AMR activity undetected by histology could be operating in some early biopsies.

Methods: Transcriptome of kidney allograft biopsies performed within the first month in presensitized patients (DSA⁺) who had received desensitization and did not develop active/probable AMR by histology (R^-) was compared with biopsies showing active/probable AMR (R⁺/DSA⁺). As negative controls, biopsies without rejection by histology in patients without DSA at transplantation were used (R^-/DSA^-). RNA sequencing from biopsies selected from the biobank was used in cohort 1 (n = 32) and microarray, including the molecular microscope (Molecular Microscope Diagnostic System [MMDx]) algorithm, in recent cohort 2 (n = 30).

Results: The transcriptome of R^-/DSA⁺ was similar to R⁺/DSA⁺ as these groups differed in 14 transcripts only. Contrarily, large differences were found between both DSA⁺ groups and negative controls. Fast gene set enrichment analyses showed upregulation of the immune system in both DSA⁺ groups (gene ontology terms: adaptive immune response, humoral immune response, antigen receptor-mediated signaling, and B-cell receptor signaling or complement activation) when compared with negative controls. MMDx assessment in cohort 2 classified 50% of R^-/DSA⁺ samples as AMR and found no differences in AMR molecular scores between R⁺ and R^- DSA⁺ groups. In imlifidase desensitization, MMDx series showed a gradual increase in AMR scores over time.

Conclusions: Presensitized kidney transplant recipients exhibited frequent molecular calls of AMR in biopsy-based transcript diagnostics despite desensitization therapy and negative histology.

Background: In organ transplantation, cold ischemia is associated with sterile inflammation that subsequently conditions adaptive immunity directed against the grafts during revascularization. This inflammation is responsible for venous thrombosis, which is the main postoperative complication affecting graft function. Our aim was to investigate the modulation of immune responses and endothelial function of pancreatic grafts during cold ischemia using different preservation modalities.

Methods: According to a preclinical porcine model of controlled donation after circulatory death, pancreatic grafts were preserved under hypothermic conditions for 24 h according to 4 modalities: static cold storage, hypothermic machine perfusion, hypothermic oxygenated perfusion at 21%, and 100%. Biopsies of the head and tail of the pancreas were performed during preservation. The first step involved a broad screening of the gene expression profile (84 genes) during preservation on a limited number of grafts. In the second step, a confirmation test was performed in all 4 groups.

Results: Vascular endothelial growth factor gene expression showed a decrease during preservation in the hypothermic oxygenated perfusion 21% and 100% groups compared with the static cold storage group. In contrast, thrombomodulin gene expression showed an increase during preservation in the hypothermic oxygenated perfusion 21% and 100% groups compared with the static cold storage and hypothermic machine perfusion groups.

Conclusions: We demonstrated that compared with static cold storage, hypothermic oxygenated perfusion is an effective modality for modulating endothelial function by increasing thrombomodulin expression and decreasing ischemia and vascular endothelial growth factor expression.