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Whole blood RNA sequencing of African American kidney transplant recipients from VericiDx cohort

ABSTRACT: The VericiDx cohort is an ongoing clinical trial (241 patients (32.0% self-reported AA) enrolled as of 06/30/2023) with a focus on predicting early acute rejection and renal fibrosis post-transplantation (ClinicalTrials.gov: NCT04727788).

ORGANISM(S): Homo sapiens

PROVIDER: GSE281721 | GEO | 2024/12/26

REPOSITORIES: GEO

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Emory University African American Microbiome in Pregnancy Cohort.

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Emory University African American Microbiome in Pregnancy Cohort [Methylation]

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Neonatal Blood Spots from the Emory University African American Microbiome in Pregnancy Cohort

Project description:Newborn screening blood spots were obtained for neonates born to women enrolled in the Emory University African American Microbiome in Pregnacy Cohort

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Transplant Center Variability in Disparities for African-American Kidney Transplant Recipients.

Project description:BACKGROUND Disparities research has traditionally focused on patient-level variables to ascertain predominant risk factors driving differences in outcomes for African-American (AA) kidney transplant recipients. Our objectives were to determine the magnitude and impact of transplant center variability for graft outcome disparities. MATERIAL AND METHODS This was a retrospective cohort study analyzing 25 years of U.S. national transplant registry data at both the patient and center levels using univariate descriptive statistics and multivariable modeling. RESULTS A total of 257,024 recipients from 191 centers were analyzed; AAs represented 31.1% of recipients. After adjusting for baseline characteristics, AAs had 42% higher risk of graft loss (aHR 1.42, 95% CI 1.39 to 1.45; p<0.001). Center variability for graft outcome disparities in AAs was significant (race*center interaction term p<0.05), with the aHRs ranging from 0.5 to 4.9; 46% of centers demonstrated a non-statistically significant disparity (aHR p>0.05) and 25% of centers had a large AA disparity (aHR >1.75). In a more recent transplant time period (2000-14), overall racial disparities decreased but center-level disparities increased in variability. Center-level factors significantly associated with increasing disparity included higher acute rejection rates, fewer transplants per year, longer length of stay, lower use of calcineurin inhibitors (CNI), and lower living donor rates. CONCLUSIONS There is evidence of significant center-level variability in graft outcome disparities for AA kidney recipients. Further, there appears to be a number of center-level factors associated with this variability, including acute rejection rates, CNI use, number of transplants per year, and, in recent years, low living donor rates.

| S-EPMC6019128 | biostudies-literature

Genotype-guided tacrolimus dosing in African-American kidney transplant recipients.

Project description:Tacrolimus is dependent on CYP3A5 enzyme for metabolism. Expression of the CYP3A5 enzyme is controlled by several alleles including CYP3A5*1, CYP3A5*3, CYP3A5*6 and CYP3A5*7. African Americans (AAs) have on average higher tacrolimus dose requirements than Caucasians; however, some have requirements similar to Caucasians. Studies in AAs have primarily evaluated the CYP3A5*3 variant; however, there are other common nonfunctional variants in AAs (CYP3A5*6 and CYP3A5*7) that do not occur in Caucasians. These variants are associated with lower dose requirements and may explain why some AAs are metabolically similar to Caucasians. We created a tacrolimus clearance model in 354 AAs using a development and validation cohort. Time after transplant, steroid and antiviral use, age and CYP3A5*1, *3, *6 and *7 alleles were significant toward clearance. This study is the first to develop an AA-specific genotype-guided tacrolimus dosing model to personalize therapy.

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Donor Risk Index for African American liver transplant recipients with hepatitis C virus.

Project description:UnlabelledAfrican American (AA) liver transplant (LT) recipients with hepatitis C virus (HCV) have higher rates of graft loss than other racial/ethnic groups. The Donor Risk Index (DRI) predicts graft loss but is neither race- nor disease-specific and may not be optimal for assessing donor risk for AA HCV-positive LT recipients. We developed a DRI for AA with HCV with the goal of enhancing graft loss predictions. All U.S. HCV-positive adult AA first deceased donor LTs surviving ≥30 days from March 2002 to December 2009 were included. A total of 1,766 AA LT recipients were followed for median 2.8 (interquartile range [IQR] 1.3-4.9) years. Independent predictors of graft loss were donor age (40-49 years: hazard ratio [HR] 1.54; 50-59 years: HR 1.80; 60+ years: HR 2.34, P < 0.001), non-AA donor (HR 1.66, P < 0.001), and cold ischemia time (CIT) (HR 1.03 per hour >8 hours, P = 0.03). Importantly, the negative effect of increasing donor age on graft and patient survival among AAs was attenuated by receipt of an AA donor. A new donor risk model for AA (AADRI-C) consisting of donor age, race, and CIT yielded 1-year, 3-year, and 5-year predicted graft survival rates of 91%, 77%, and 68% for AADRI <1.60; 86%, 67%, and 55% for AADRI 1.60-2.44; and 78%, 53%, and 39% for AADRI >2.44. In the validation dataset, AADRI-C correctly reclassified 27% of patients (net reclassification improvement P = 0.04) compared to the original DRI.ConclusionAADRI-C identifies grafts at higher risk of failure and this information is useful for risk-benefit discussions with recipients. Use of AA donors allows consideration of older donors.

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The impact of time-varying clinical surrogates on disparities in African-American kidney transplant recipients - a retrospective longitudinal cohort study.

Project description:An improved understanding of the impact of clinical surrogates on disparities in African-American (AA) kidney transplantation (KTX) is needed. We conducted a 10-year retrospective longitudinal cohort study of electronically abstracted clinical data assessing the impact of surrogates on disparities in KTX. Clinical surrogates were assessed by posttransplant year (1, 2, 3 or 4) and defined as acute rejection (Banff ≥1A), mean SBP >140 mmHg, tacrolimus variability (CV) >40%, mean glucose >160 mg/dl and mean hemoglobin <10 g/dl. We utilized landmark methodology to minimize immortal time bias and logistic and survival regression to assess outcomes; 1610 KTX were assessed (54.2% AAs), with 1000, 468, 368 and 303 included in the year 1, 2, 3 and 4 complete case analyses, respectively. AAs had significantly higher odds of developing a clinical surrogate, which increased in posttransplant years three and four [OR year 1 1.99 (1.38-2.88), year 2 1.77 (1.20-2.62), year 3 2.35 (1.49-3.71), year 4 2.85 (1.72-4.70)]. Adjusting for the five clinical surrogates in survival models explained a significant portion of the higher risks of graft loss in AAs in post-transplant years three and four. Results suggest focusing efforts on improving late clinical surrogate management within AAs may help mitigate racial disparities in KTX.

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Emory University African American Microbiome in Pregnancy Cohort

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-03-19 | GSE107460 | GEO

Genomewide Association Study of Tacrolimus Concentrations in African American Kidney Transplant Recipients Identifies Multiple CYP3A5 Alleles.

Project description:We previously reported that tacrolimus (TAC) trough blood concentrations for African American (AA) kidney allograft recipients were lower than those observed in white patients. Subtherapeutic TAC troughs may be associated with acute rejection (AR) and AR-associated allograft failure. This variation in TAC troughs is due, in part, to differences in the frequency of the cytochrome P450 CYP3A5*3 allele (rs776746, expresses nonfunctional enzyme) between white and AA recipients; however, even after accounting for this variant, variability in AA-associated troughs is significant. We conducted a genomewide association study of TAC troughs in AA kidney allograft recipients to search for additional genetic variation. We identified two additional CYP3A5 variants in AA recipients independently associated with TAC troughs: CYP3A5*6 (rs10264272) and CYP3A5*7 (rs41303343). All three variants and clinical factors account for 53.9% of the observed variance in troughs, with 19.8% of the variance coming from demographic and clinical factors including recipient age, glomerular filtration rate, anticytomegalovirus drug use, simultaneous pancreas-kidney transplant and antibody induction. There was no evidence of common genetic variants in AA recipients significantly influencing TAC troughs aside from the CYP3A gene. These results reveal that additional and possibly rare functional variants exist that account for the additional variation.

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