The combined risk of donor quality and recipient age: higher-quality kidneys may not always improve patient and graft survival.
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ABSTRACT:
SUBMITTER: Hernandez RA
PROVIDER: S-EPMC4455544 | biostudies-other | 2014 Nov
REPOSITORIES: biostudies-other
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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:IntroductionOwing to organ shortage, the number of kidney transplantation (KT) involving older adult living donors is increasing. We aimed to investigate the effects of living-donor age and donor-recipient age differences on KT outcomes.MethodsThis single-center, retrospective cohort study involved 853 adult LDKTs performed between January 2008 and December 2018. Recipients were stratified into the following 5 groups based on donor age and donor-recipient age difference: donor age, 30 to 49 years and age difference, -10 to 15 years; donor age, 50 to 69 years and age difference, -10 to 15 years; donor age, 50 to 69 years and age difference, 15 to 40 years; donor age, 70 to 89 years and age difference, -10 to 15 years; and donor age, 70 to 89 years and age difference, 15 to 40 years (groups 1, 2, 3, 4, and 5, respectively). As a primary outcome, the risk of graft loss was investigated. The secondary outcomes were postoperative estimated glomerular filtration rates (eGFRs) and mortality rates of recipients.ResultsGroup 4, representing KT between older adult donors and older adult recipients, had the highest graft loss risk and mortality. The eGFRs of the recipients from donors aged 70 to 89 years (groups 4 and 5) were significantly lower than those from donors in the other groups. Although the differences in the eGFR between groups 4 and 5 were not significant, the eGFR of group 4 was lower than that of group 5 at 6 months post-KT.ConclusionLDKTs from older adult donors to older adult recipients resulted in the worst graft survival and mortality rates.
| S-EPMC8640566 | 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:BackgroundCurrent 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 designWe 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.ResultsFrom 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).ConclusionsModifiable 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.
| S-EPMC7483537 | biostudies-literature
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.
| S-EPMC6324912 | biostudies-literature
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:BackgroundThe new deceased donor kidney allocation algorithm uses a Kidney Donor Profile Index (KDPI) based on donor characteristics to predict graft survival and divides kidneys into 4 quality groups (ie, KDPI-A, -B, -C, and -D). Pediatric kidneys constitute 10% to 12% of deceased donor kidneys. We hypothesized that KDPI would not accurately predict pediatric donor graft survival and superior predictive models could be created.MethodsScientific Registry of Transplant Recipients data for years 2000 to 2010 for transplants from child (<10 years) and adolescent (10-17 years inclusive) donors into first-time adult recipients were analyzed with graft failure as the principle outcome. Two novel indices, Child Donor Index (CDI) and Adolescent Donor Index (ADI), were developed using stepwise variable deletion to identify significant model covariates in a Cox Regression. Pediatric donor kidneys were then classified into the 4 quality groups based on both KDPI and CDI/ADI scores. The performance of the KDPI, CDI, and ADI models were compared with respect to the 4 quality groups defined by the new allocation system.ResultsThe KDPI did not effectively discriminate between quality groups (P > 0.05 for all but 1 comparison) in Kaplan-Meier survival analyses. The CDI and ADI included novel variables (eg, body mass index percentiles) and successfully discriminated between quality groups (P < 0.05 by log rank test). The Net Reclassification Index showed improvement when switching from KDPI to CDI and ADI, with values of 0.09 (P < 0.001) and 0.073 (P < 0.001), respectively.ConclusionsThe KDPI does not accurately predict pediatric kidney graft survival. Alternative indices can improve allocation efficiency.
| S-EPMC4940335 | 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:Transplantation and pregnancy, in which two diploid genomes reside in one body, can each lead to diseases in which immune cells from one individual target antigens encoded in the other's genome. One such disease, graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT, or bone marrow transplant), is common even after transplants between HLA-identical siblings, indicating that cryptic histocompatibility loci exist outside the HLA locus. The immune system of an individual whose genome is homozygous for a gene deletion could recognize epitopes encoded by that gene as alloantigens. Analyzing common gene deletions in three HSCT cohorts (1,345 HLA-identical sibling donor-recipient pairs), we found that risk of acute GVHD was greater (odds ratio (OR) = 2.5; 95% confidence interval (CI) 1.4-4.6) when donor and recipient were mismatched for homozygous deletion of UGT2B17, a gene expressed in GVHD-affected tissues and giving rise to multiple histocompatibility antigens. Human genome structural variation merits investigation as a potential mechanism in diseases of alloimmunity.
| S-EPMC2804745 | biostudies-literature
Project description:For decades, the osteogenic effect from different physical activities on bone in rodents remained uncertain. This literature review presents for the first time the effects on five exercise models (treadmill running, wheel running, swimming, resistance training and vibration modes) in three different experimental rat groups (males, females, osteopenic) on bone quality. The bone parameters presented are bone mineral density, micro-architectural and mechanical properties, and osteoblast/osteocyte and osteoclast parameters. This review shows that physical activities have a positive effect (65% of the results) on bone status, but we clearly observed a difference amongst the different protocols. Even if treadmill running is the most used protocol, the resistance training constitutes the first exercise model in term of osteogenic effects (87% of the whole results obtained on this model). The less osteogenic model is the vibration mode procedure (31%). It clearly appears that the gender plays a role on the bone response to swimming and wheel running exercises. Besides, we did not observe negative results in the osteopenic population with impact training, wheel running and vibration activities. Moreover, about osteoblast/osteocyte parameters, we conclude that high impact and resistance exercise (such jumps and tower climbing) seems to increase bone formation more than running or aerobic exercise. Among the different protocols, literature has shown that the treadmill running procedure mainly induces osteogenic effects on the viability of the osteocyte lineage in both males and females or ovariectomized rats; running in voluntary wheels contributes to a negative effect on bone metabolism in older male models; whole-body vertical vibration is not an osteogenic exercise in female and ovariectomized rats; whereas swimming provides controversial results in female models. For osteoclast parameters only, running in a voluntary wheel for old males, the treadmill running program at high intensity in ovariectomized rats, and the swimming program in a specific ovariectomy condition have detrimental consequences.
| S-EPMC7598192 | biostudies-literature