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Effect of developmental stage of HSC and recipient on transplant outcomes.

ABSTRACT: The first hematopoietic stem cells (HSCs) that engraft irradiated adult mice arise in the aorta-gonad-mesonephros (AGM) on embryonic day 11.5 (E11.5). However, at this stage, there is a discrepancy between the apparent frequency of HSCs depicted with imaging and their rarity when measured with limiting dilution transplant. We have attempted to reconcile this difference using neonatal recipients, which are more permissive for embryonic HSC engraftment. We found that embryonic HSCs from E9.5 and E10.5 preferentially engrafted neonates, whereas developmentally mature, definitive HSCs from E14.5 fetal liver or adult bone marrow (BM) more robustly engrafted adults. Neonatal engraftment was enhanced after treating adult BM-derived HSCs with interferon. Adult BM-derived HSCs preferentially homed to the liver in neonatal mice yet showed balanced homing to the liver and spleen in adults. These findings emphasize the functional differences between nascent and mature definitive HSCs.

SUBMITTER: Arora N

PROVIDER: S-EPMC4172398 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Effect of developmental stage of HSC and recipient on transplant outcomes.

Arora Natasha N Wenzel Pamela L PL McKinney-Freeman Shannon L SL Ross Samantha J SJ Kim Peter G PG Chou Stephanie S SS Yoshimoto Momoko M Yoder Mervin C MC Daley George Q GQ

Developmental cell 20140601 5

The first hematopoietic stem cells (HSCs) that engraft irradiated adult mice arise in the aorta-gonad-mesonephros (AGM) on embryonic day 11.5 (E11.5). However, at this stage, there is a discrepancy between the apparent frequency of HSCs depicted with imaging and their rarity when measured with limiting dilution transplant. We have attempted to reconcile this difference using neonatal recipients, which are more permissive for embryonic HSC engraftment. We found that embryonic HSCs from E9.5 and E ...[more]

PMID: 24914562

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Project description:Rationale & objectiveKidney function can be adversely affected by significant tricuspid regurgitation (TR) owing to effects on cardiac output and systemic venous congestion. However, the impact of significant TR on short- and long-term kidney function following a kidney transplant remains uncertain.Study designRetrospective observational cohort.Setting & participantsKidney transplant recipients from a single center between 2016 and 2019.ExposureSignificant TR, defined by at least moderate regurgitation, on echocardiogram before kidney transplantation.OutcomesPrimary end points included the estimated glomerular filtration rate (eGFR) at the following 3 time points: 2 weeks, 3 months, and 1 year after transplantation. Secondary end points included major adverse cardiac events including nonfatal myocardial infarction, all-cause mortality, and hospitalization owing to cardiovascular disease.Analytical approachPropensity score matching was performed in 1:3 ratio between patients treated with significant TR and controls, within a caliper 0.05 standard deviation of the propensity score, to analyze for the primary end point.ResultsAmong 557 kidney transplant recipients, 26 (5%) exhibited significant TR pretransplantation. According to propensity score matching analysis, with 1:3 ratio between 24 patients with significant TR and 72 controls, the presence of significant TR was associated with a lower eGFR posttransplantation. Specifically, the mean eGFR was 41.2 mL/min/1.73 m2 compared to 53.3 mL/min/1.73 m2 at 2 weeks (P < 0.01), 50.0 mL/min/1.73 m2 versus 60.3 mL/min/1.73 m2 at 3 months (P < 0.01), and 49.4 mL/min/1.73 m2 versus 61.2 mL/min/1.73 m2 at 1 year (P < 0.01). Delayed graft function was observed in 41.7% of the patients with significant TR compared to 12.5% of those without significant TR (P < 0.01). No patients with significant TR required dialysis after 1 year. 1-year major adverse cardiac events were nonsignificantly higher among patients with significant TR (20.8% vs 8.1%; P = 0.16).LimitationsRetrospective design and relatively small TR population.ConclusionsThe presence of significant TR among kidney transplant recipients was associated with a lower eGFR at 2 weeks, 3 months, and 1 year following transplant, although all remained dialysis independent at 1 year.

Project description:INTRODUCTION:Certain ABO blood types have been linked to cardiovascular disease, infection and cancers. The effect of recipient ABO blood group on patient and graft survival has not been studied in ABO-matched kidney transplantation. This study aims to determine the association between kidney transplant recipient ABO blood groups with patient and graft survival in Australian and New Zealand. METHODS:All Australian and New Zealand transplant recipients who received ABO-compatible primary kidney transplants between 1995-2016 were analysed using a de-identified dataset from the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. Primary analysis was undertaken of recipient ABO blood group O versus non-O blood groups. The primary outcome was patient survival post kidney transplantation and the secondary outcome was death censored graft survival. Recipient age at first transplant, gender, ethnicity, body mass index, smoking status, vascular disease, presence of diabetes mellitus, chronic lung disease, primary kidney disease, donor source, donor age and gender, and era of transplants were included in the multivariate model as confounders. RESULTS AND CONCLUSIONS:On analysis of 15,523 kidney transplant recipients, blood group O was not associated with patient survival (hazard ratio (HR) 0.96, 95% confidence interval (CI) 0.89-1.04) nor death censored graft survival (HR 0.97, 95% CI 0.89-1.05) compared to non-blood group O recipients. Competing risks analyses showed an increased risk of cancer-related mortality in blood group O recipients on univariate analyses (HR 1.18, 95% CI 1.01-1.37) however, this became insignificant on multivariate analyses. On secondary analyses, recipient blood group AB (4.11% participants) was associated with inferior death censored graft survival compared to those with blood group O (HR 1.24, 95% CI 1.02-1.50). Although recipient ABO blood groups were not associated with patient nor graft survival, differences in cause-specific mortality between individual blood groups cannot be excluded based on current analyses.

Project description:Background:Nephron endowment in renal transplantation is infrequently considered, but may have important implications for post kidney transplantation outcomes. In this population-cohort study, we analyzed the deceased-donor kidney transplant outcomes stratified by donor-to-recipient size ratios. Methods:Data for all deceased-donor adult kidney transplantation recipients between 2003 and 2015 were extracted from the UK Transplant Registry. We used weight as a surrogate marker for kidney size and defined the following mismatch categories (donor weight/recipient weight × 100): less than 75% (small donor kidney), 75% to 125% (weight matched kidney), and greater than 125% (large donor kidney). Univariable and multivariable analyses were undertaken to assess the relationship between this marker and patient outcomes. Results:Outcomes for 11 720 transplants were analyzed with weight mismatch stratified as follows; small donor kidney (n = 1608, 13.7%), weight matched kidney (n = 7247, 61.8%) and large donor kidney (n = 2865, 24.4%). On multivariable analysis, no significant differences were detected in overall (P = 0.876) or death-censored (P = 0.173) graft survival, or in rates of delayed graft function (P = 0.396) between these 3 groups. However, 12-month creatinine levels were found to decline progressively across the groups (P < 0.001), with adjusted averages of 144.2 ?mol/L for recipients of small donor kidneys, 134.7 ?mol/L in weight matched kidneys, and 124.9 ?mol/L in recipients of large donor kidneys. In addition, patient survival was found to be significantly shorter in recipients of larger kidneys than those with weight matched kidneys (hazard ratio, 1.21; 95% confidence interval, 1.05-1.40; P = 0.009), which is inconsistent with the existing literature. Conclusions:Our data demonstrate that 12-month creatinine is influenced by donor-to-recipient difference in body weight, but that no such difference is observed for either delayed graft function or death-censored graft survival. However, we observed increased mortality in recipients receiving larger kidneys; an observation which conflicts with the existing literature and warrants further investigation.

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Effect of developmental stage of HSC and recipient on transplant outcomes.

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Effect of developmental stage of HSC and recipient on transplant outcomes.

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