Impact of Deceased Donor Management on Donor Heart Use and Recipient Graft Survival.
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ABSTRACT: Background
Current risk-adjusted models used to predict donor heart use and cardiac graft survival from organ donors after brain death (DBDs) do not include bedside critical care data. We sought to identify novel independent predictors of heart use and graft survival to better understand the relationship between donor management and transplantation outcomes.Study design
We conducted a prospective observational study of DBDs managed from 2008 to 2013 by 10 organ procurement organizations. Demographic data, critical care parameters, and treatments were recorded at 3 standardized time points during donor management. The primary outcomes measures were donor heart use and cardiac graft survival.Results
From 3,433 DBDs, 1,134 hearts (33%) were transplanted and 969 cardiac grafts (85%) survived after 684 ± 392 days of follow-up. After multivariable analysis, independent positive predictors of heart use included standard criteria donor status (odds ratio [OR] 3.93), male sex (OR 1.68), ejection fraction > 50% (OR 1.64), and partial pressure of oxygen to fraction of inspired oxygen ratio > 300 (OR 1.31). Independent negative predictors of heart use included donor age (OR 0.94), BMI > 30 kg/m2 (OR 0.78), serum creatinine (OR 0.83), and use of thyroid hormone (OR 0.78). As for graft survival, after controlling for known recipient risk factors, thyroid hormone dose was the only independent predictor (OR 1.04 per μg/h).Conclusions
Modifiable critical care parameters and treatments predict donor heart use and cardiac graft survival. The discordant relationship between thyroid hormone and donor heart use (negative predictor) vs cardiac graft survival (positive predictor) warrants additional investigation.
SUBMITTER: Swanson EA
PROVIDER: S-EPMC7483537 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Importance:The shortage of deceased donor kidneys for transplants is an ongoing concern. Prior studies support transplanting kidneys from deceased donors with acute kidney injury (AKI), but those investigations have been subject to selection bias and small sample sizes. Current allocation practices of AKI kidneys in the United States are not well characterized. Objectives:To evaluate the association of deceased donor AKI with recipient graft survival and to characterize recovery and discard practices for AKI kidneys by organ procurement organizations. Design, Setting, and Participants:Registry-based, propensity score-matched cohort study from January 1, 2010, to December 31, 2013, in the United States. The dates of analysis were March 1 to November 1, 2019. From 2010 to 2013, a total of 6832 deceased donors with AKI and 15 310 deceased donors without AKI had at least 1 kidney transplanted. This study used a 1:1, propensity score-matched analysis to match deceased donors with AKI to deceased donors without AKI and investigated outcomes in their corresponding kidney recipients. Exposure:Deceased donor AKI, defined as at least 50% or 0.3-mg/dL increase in terminal serum creatinine level from admission. Main Outcomes and Measures:Recipients were assessed for the time to death-censored graft failure and the following secondary outcomes: delayed graft function, primary nonfunction, and the time to all-cause graft failure. Results:Ninety-eight percent (6722 of 6832) of deceased donors with AKI were matched to deceased donors without AKI. The mean (SD) age of the 13 444 deceased donors was 40.4 (14.4) years, and 63% (8529 of 13 444) were male. A total of 25 323 recipients were analyzed (15 485 [61%] were male), and their mean (SD) age was 52.0 (14.7) years. Recipients were followed up for a median of 5 (interquartile range, 4-6) years. Deceased donor AKI status had no association with death-censored graft failure (hazard ratio, 1.01; 95% CI, 0.95-1.08) or all-cause graft failure (hazard ratio, 0.97; 95% CI, 0.93-1.02). The results were consistent after examining by AKI stage and adjusting for recipient and transplant characteristics. More recipients of AKI kidneys developed delayed graft function (29% vs 22%, P < .001). Few recipients (120 of 25 323 [0.5%]) developed primary nonfunction regardless of deceased donor AKI status. Recovery and transplantation of AKI kidneys varied by organ procurement organization; most (39 of 58) had high recovery and high discard of AKI kidneys. Conclusions and Relevance:Deceased donor AKI kidneys transplanted in the study period had recipient graft survival comparable to that of non-AKI kidneys. This study's findings suggest that the transplant community should evaluate whether currently discarded AKI kidneys from donors without substantial comorbidities can be used more effectively.
| S-EPMC6991314 | biostudies-literature
Project description:This study evaluated the combined effect of recipient-to-donor weight and sex mismatch after deceased-donor renal transplantation in a German transplant cohort and the evolution of recipient-to-donor weight difference over a 13-year observation period. The association of absolute weight and sex difference with graft failure was explored in an outpatient cohort of deceased-donor transplant recipients who underwent kidney transplantation between 2000 and 2012. Graft failure was defined as repeated need for dialysis or death with a functioning graft. Recipient and donor sex pairings were classified as sex concordant (MDMR/FDFR) or discordant (MDFR/FDMR). These classes were further stratified into four groups according to recipient-to-donor weight mismatch ≥10 kg (recipient > donor) or <10 kg (recipient < donor). Multivariable Cox proportional hazards models were applied to evaluate the time to graft loss adjusting for donor, immunologic, surgical, organizational, and recipient predictors. Sex-concordant transplant pairings <10 kg weight difference served as the reference group. Among 826 transplant recipients, 154 developed graft failure (18.6%). Median graft survival time was 3.9 years; first quartile (0.2-1.2), second quartile (1.2-2.9), third quartile (2.9-5.8), and fourth quartile (5.8-12.4). After multivariable adjustment, the highest relative hazard for graft failure was observed for sex-discordant transplant pairings with a ≥10 kg weight difference between recipient and donor (compared to the reference group MDMR/FDFR with weight difference <10 kg, MDMR/FDFR with weight difference ≥10 kg, hazard ratio 1.86, 95% confidence interval 1.07-3.32-p = 0.029; MDFR/FDMR with weight difference <10 kg, hazard ratio 1.14, 95% confidence interval 0.78-1.68-p = 0.507, and MDFR/FDMR with weight difference ≥10 kg, hazard ratio 2.00, 95% confidence interval 1.15-3.48-p = 0.014). A recipient-to-donor weight mismatch of ≥10 kg was associated with an increased risk of graft loss or recipient death with a functioning graft. Concurrent sex discordance seemed to enhance this effect as indicated by an increase in the hazard ratio. We detected no significant tendency for increasing recipient-to-donor weight differences from 2000 to 2012.
| S-EPMC6440625 | biostudies-literature
Project description:BackgroundMyosteatosis is associated with perioperative outcomes in orthotopic liver transplantation (OLT). Here, we investigated the effects of body composition and myosteatosis on long-term graft and patient survival following OLT.MethodsClinical data from 225 consecutive OLT recipients from a prospective database were retrospectively analysed (May 2010 to December 2017). Computed tomography-based lumbar skeletal muscle index (SMI) (muscle mass) and mean skeletal muscle radiation attenuation (SM-RA) (myosteatosis) were calculated using a segmentation tool (3D Slicer). Patients with low skeletal muscle mass (low SMI) and myosteatosis (low SM-RA) were identified using predefined and validated cut-off values.ResultsThe mean donor and recipient age was 55 ± 16 and 54 ± 12 years, respectively. Some 67% of the recipients were male. The probability of graft and patient survival was significantly lower in patients with myosteatosis compared with patients with higher SM-RA values (P = 0.011 and P = 0.001, respectively). Low skeletal muscle mass alone was not associated with graft and patient survival (P = 0.273 and P = 0.278, respectively). Dividing the cohort into quartiles, based on the values of SMI and SM-RA, resulted in significant differences in patient but not in graft survival (P = 0.011). Even though multivariable analysis identified low SM-RA as an important prognostic marker (hazard ratio: 2.260, 95% confidence interval: 1.177-4.340, P = 0.014), myosteatosis lost its significance when early mortality (90 days) was excluded from the final multivariable model. Patients with myosteatosis showed significantly higher all-cause mortality and in particular higher rates of deaths due to respiratory and septic complication (P = 0.002, P = 0.022, and P = 0.049, respectively).ConclusionsPreoperative myosteatosis may be an important prognostic marker in patients undergoing deceased donor liver transplantation. The prognostic value of myosteatosis seems to be particularly important in the early post-operative phase. Validation in prospective clinical trials is warranted.
| S-EPMC8061365 | biostudies-literature
Project description:PurposeWe sought to build prediction models for organ transplantation and recipient survival using both biomarkers and clinical information.Materials and methodsWe abstracted clinical variables from a previous randomized trial (n = 556) of donor management. In a subset of donors (n = 97), we measured two candidate biomarkers in plasma at enrollment and just prior to explantation.ResultsSecretory leukocyte protease inhibitor (SLPI) was significant for predicting liver transplantation (C-statistic 0.65 (0.53, 0.78)). SLPI also significantly improved the predictive performance of a clinical model for liver transplantation (integrated discrimination improvement (IDI): 0.090 (0.009, 0.210)). For other organs, clinical variables alone had strong predictive ability (C-statistic >0.80). Recipient 3-years survival was 80.0% (71.9%, 87.0%). Donor IL-6 was significantly associated with recipient 3-years survival (adjusted Hazard Ratio (95%CI): 1.26(1.08, 1.48), P = .004). Neither clinical variables nor biomarkers showed strong predictive ability for 3-year recipient survival.ConclusionsPlasma biomarkers in neurologically deceased donors were associated with organ use. SLPI enhanced prediction within a liver transplantation model, whereas IL-6 before transplantation was significantly associated with recipient 3-year survival. Clinicaltrials.gov: NCT00987714.
| S-EPMC6294437 | biostudies-literature
Project description:Background. Scarcity of grafts for kidney transplantation (KTX) caused an increased consideration of deceased donors with substantial risk factors. There is no agreement on which ones are detrimental for overall graft-survival. Therefore, we investigated in a nationwide multicentre study the impact of donor and recipient related risks known before KTX on graft-survival based on the original data used for allocation and graft acceptance. Methods. A nationwide deidentified multicenter study-database was created of data concerning kidneys donated and transplanted in Germany between 2006 and 2008 as provided by the national organ procurement organization (Deutsche Stiftung Organtransplantation) and BQS Institute. Multiple Cox regression (significance level 5%, hazard ratio [95% CI]) was conducted (n = 4411, isolated KTX). Results. Risk factors associated with graft-survival were donor age (1.020 [1.013-1.027] per year), donor size (0.985 [0.977-0.993] per cm), donor's creatinine at admission (1.002 [1.001-1.004] per µmol/L), donor treatment with catecholamine (0.757 [0.635-0.901]), and reduced graft-quality at procurement (1.549 [1.217-1.973]), as well as recipient age (1.012 [1.003-1.021] per year), actual panel reactive antibodies (1.007 [1.002-1.011] per percent), retransplantation (1.850 [1.484-2.306]), recipient's cardiovascular comorbidity (1.436 [1.212-1.701]), and use of IL2-receptor antibodies for induction (0.741 [0.619-0.887]). Conclusion. Some donor characteristics persist to impact graft-survival (e.g., age) while the effect of others could be mitigated by elaborate donor-recipient match and care.
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Project description:BackgroundIn kidney transplantation, nonimmunologic donor-recipient (D-R) pairing is generally not given the same consideration as immunologic matching. The aim of this study was to determine how nonimmunologic D-R pairing relates to independent donor and recipient factors, and to immunologic HLA match for predicting graft loss.MethodsSeven D-R pairings (race, sex, age, weight, height, cytomegalovirus serostatus, and HLA match) were assessed for their association with the composite outcome of death or kidney graft loss using a Cox regression-based forward stepwise selection model. The best model for predicting graft loss (including nonimmunologic D-R pairings, independent D-R factors, and/or HLA match status) was determined using the Akaike Information Criterion.ResultsTwenty three thousand two hundred sixty two (29.9%) people in the derivation data set and 9892 (29.7%) in the validation data set developed the composite outcome of death or graft loss. A model that included both independent and D-R pairing variables best predicted graft loss. The c-indices for the derivation and validation models were 0.626 and 0.629, respectively. Size mismatch (MM) between donor and recipient (>30 kg [D < R} and >15 cm [D < R]) was associated with poor patient and graft survival even with 0 HLA MM, and conversely, an optimal D-R size pairing mitigated the risk of graft loss seen with 6 HLA MM.ConclusionsD-R pairing is valuable in predicting patient and graft outcomes after kidney transplant. D-R size matching could offset the benefit and harm seen with 0 and 6 HLA MM, respectively. This is a novel finding.
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Project description:Background and objectivesSmall donor and/or kidney sizes relative to recipient size are associated with a higher risk of kidney allograft failure. Donor and recipient ages are associated with graft survival and may modulate the relationship between size mismatch and the latter. The aim of this study was to determine whether the association between donor-recipient size mismatch and graft survival differs by donor and recipient age.Design, setting, participants, & measurementWe performed a retrospective cohort study of first adult deceased donor kidney transplantations performed between 2000 and 2018 recorded in the Scientific Registry of Transplant Recipients. We used multivariable Cox proportional hazards models to assess the association between donor-recipient body surface area ratio and death-censored graft survival, defined as return to dialysis or retransplantation. We considered interactions between donor-recipient body surface area ratio and each of recipient and donor age.ResultsAmong the 136,321 kidney transplant recipients included in this study, 23,614 (17%) experienced death-censored graft loss over a median follow-up of 4.3 years (interquartile range, 1.9-7.8 years). The three-way donor-recipient body surface area ratio by donor age by recipient age interaction was statistically significant (P=0.04). The magnitude of the association between severe size mismatch (donor-recipient body surface area ratio <0.80 versus ≥1.00) and death-censored graft survival was stronger with older donor age and recipient age. In all recipient age categories except the youngest (18-30 years), 5- and 10-year graft survival rates were similar or better with a size-mismatched donor aged <40 years than a nonsize-mismatched donor aged 40 years or older.ConclusionsThe association of donor-recipient size mismatch on long-term graft survival is modulated by recipient and donor age. Size-mismatched kidneys yield excellent graft survival when the donor is young. Donor age was more strongly associated with graft survival than size mismatch.
| S-EPMC7536765 | biostudies-literature
Project description:BackgroundThe effect of donor-recipient human leukocyte antigen (HLA) matching on outcomes remains relatively unexplored in pediatric patients. The objective of this study was to investigate the effects of donor-recipient HLA matching on graft survival in pediatric heart transplantation.Methods and resultsThe UNOS (United Network for Organ Sharing) database was queried for heart transplants occurring between October 31, 1987, and December 31, 2012, in a recipient aged ≤17 years with ≥1 postoperative follow-up visit. Retransplants were excluded. Transplants were divided into 3 donor-recipient matching groups: no HLA matches (HLA-no), 1 or 2 HLA matches (HLA-low), and 3 to 6 HLA matches (HLA-high). Primary outcome was graft loss. Four thousand four hundred seventy-one heart transplants met the study inclusion criteria. High degree of donor-recipient HLA matching occurred infrequently: HLA-high (n=269; 6%) versus HLA-low (n=2683; 60%) versus HLA-no (n=1495; 34%). There were no differences between HLA matching groups in the frequency of coronary vasculopathy (P=0.19) or rejection in the first post-transplant year (P=0.76). Improved graft survival was associated with a greater degree of HLA donor-recipient matching: HLA-high median survival, 17.1 (95% confidence interval, 14.0-20.2) years; HLA-low median survival, 14.2 (13.1-15.4) years; and HLA-no median survival, 12.1 (10.9-13.3 years) years; P<0.01, log-rank test. In Cox-regression analysis, HLA matching was independently associated with decreased graft loss: HLA-low versus HLA-no hazard ratio, 0.86 (95% confidence interval, 0.74-0.99), P=0.04; HLA-high versus HLA-no, 0.62 (95% confidence interval, 0.43-0.90), P<0.01.ConclusionsDecreased graft loss in pediatric heart transplantation was associated with a higher degree of donor-recipient HLA matching, although a difference in the frequency of early rejection or development of coronary artery vasculopathy was not seen.
| S-EPMC4102664 | biostudies-literature
Project description:BackgroundThe impact of selecting older donors for living donor liver transplantation (LDLT) in the United States is incompletely studied, particularly in light of the recent expansion of LDLT nationally.MethodsAdult LDLTs from January 01, 2005 to December 31, 2019 were identified using the United Network for Organ Sharing database. Multivariable Cox models evaluated living donor (LD) age as a predictor of LDLT recipient and graft survival. The impact of increasing donor age on recipient outcomes was compared between LD and deceased donor recipients. Donor postoperative outcomes were evaluated.ResultsThere were 3539 LDLTs at 65 transplant centers during the study period. Despite the recent expansion of LDLT, the proportion of LDs aged ≥50 y was stable. There were no clinically significant differences in recipient or donor characteristics by LD age group. LD age ≥50 y was associated with an adjusted hazard ratio of 1.49 ( P = 0.012) for recipient survival and 1.61 ( P < 0.001) for graft survival (vs LDs aged 18-29 y). The negative impact of increasing donor age on graft survival was more profound after LDLT than deceased donor liver transplantation (interaction P = 0.019). There was a possible increased rate of early donor biliary complications for donors >55 y (7.1% versus 3.1% for age <40 y; P = 0.156).ConclusionsIncreasing LD age is associated with decreased recipient and graft survival, although older donors still largely yield acceptable outcomes. Donor outcomes were not clearly impacted by increasing age, though this warrants further study.
| S-EPMC9771867 | biostudies-literature
Project description:We aimed to characterize patterns of differences in heart graft failure rates by recipient sex, accounting for modifying effects of donor sex and recipient age.MethodsWe evaluated 69 246 first heart transplant recipients (1988-2019; Scientific Registry of Transplant Recipients). We used multivariable time-varying Cox models, considering recipient sex by donor sex by recipient age interaction and adjusting for potential confounders. Using the hazard ratio (HR) from the models and a fixed profile of recipient and donor characteristics, we also compared fitted absolute failure rates by recipient sex.ResultsAmong recipients of male donors, female recipients of all ages had higher failure rates than males (0-12 y: HR 1.36 (95% confidence interval [CI], 1.03-1.81); 13-24 y: 1.43 [1.09-1.88]; 25-44 y: 1.22 [0.95-1.57]; ≥45 y: 1.16 [1.06-1.27]); differences were statistically significant in all age intervals except 25-44 y. When the donor was male, 13 to 24-y-olds showed the largest absolute difference in fitted absolute failure rates, with rates higher by 11.3 failures per 1000 person-y in female than male recipients. Among recipients of female donors, there were no statistically significant differences in graft failure rates between female and male heart recipients of any age. Although point estimates suggested higher failure rates in female than male recipients <25 y (0-12 y: HR 1.19 [95% CI, 0.85-1.66]; 13-24 y: 1.17 [0.84-1.63]), these were not statistically significant.ConclusionsFemale recipients tended to have poorer outcomes than males, particularly at younger ages and when the donor was male, consistent with observations in kidney transplants.
| S-EPMC8425832 | biostudies-literature