Dataset Information

Observed elevated donor-derived cell free DNA in orthotopic heart transplant recipients without clinical evidence of rejection.

ABSTRACT: Donor-derived cell free DNA (dd-cfDNA) has rapidly become part of rejection surveillance following orthotopic heart transplantation. However, some patients show elevated dd-cfDNA without clinical evidence of rejection. With the aim to provide a clinical description of this subpopulation, we retrospectively analyzed 35 cardiac transplant recipients at our center who experienced elevated (≥.20%) dd-cfDNA in the absence of clinical rejection, out of a total 106 recipients who had dd-cfDNA results available during the first year. The median time to first elevated dd-cfDNA level was 46 days, and the highest dd-cfDNA recorded within 1 year was .31% [inter-quartile range, .23-.45]. Twenty-two (63%) patients experienced infections (cytomegalovirus (CMV) or other), and 16 (46%) presented with de novo donor-specific antibodies. Cluster analysis revealed four distinct groups characterized by (a) subclinical rejection with 50% CMV (n = 16), (b) non-CMV infections and the longest time to first elevated dd-cfDNA (187 days) (n = 8), (c) right ventricular dysfunction (n = 6), and (d) women who showed the youngest median age (45 years) and highest median dd-cfDNA (.50%) (n = 5). Continued prospective analysis is needed to determine if these observations warrant changes in patient management to optimize the utilization of this vital non-invasive graft surveillance tool.

SUBMITTER: Afzal A

PROVIDER: S-EPMC9286598 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:AimsSome risk assessment tools have been developed to categorize mortality risk in heart transplant recipients, but it is unclear whether these tools can be used interchangeable in different transplant regions.Methods and resultsWe performed a retrospective single-centre study in 1049 adult German heart transplant recipients under jurisdiction of Eurotransplant. Univariable and multivariable Cox regression analysis was used to generate a risk scoring system. C-statistics were used to compare our score with a US score and a French score regarding their ability to discriminate between 1 year survivors and non-survivors within our study cohort. Of 38 parameters assessed, seven recipient-specific parameters [age, height, dilated cardiomyopathy (DCM), ischaemic cardiomyopathy (ICM), total bilirubin, extracorporeal membrane oxygenation (ECMO), and biventricular assist device/total artificial heart (BVAD/TAH) implant], one donor-specific parameter (cold ischaemic time), and one recipient-independent and donor-independent other parameter (late transplant era) were statistically significant in predicting 1 year mortality. The initial score was generated by using the regression coefficients from the multivariable analysis as follows: 1.70 * ln age - 4.0 * ln height - 0.9 * diagnosis (= 1 if diagnosis = DCM) - 0.67 * diagnosis (= 1 if diagnosis = ICM) + 0.33 * ln total bilirubin + 1.74 * ln cold ischaemic time + 0.98 * mechanical circulatory support (MCS) implant (= 1 if MCS implant = ECMO) + 0.47 * MCS implant (= 1 of MCS implant = BVAD/TAH) - 0.66 * transplant era (= 1 if transplant era = 2017-2018). The initial score was converted into the Bad Oeynhausen (BO) score as a positive integer variable by means of the following formula: BO score = (initial score + 8) * 3. In patients scoring 2 to <7 points (n = 112), 7 to <11 points (n = 580), 11 to <15 points (n = 339), and 15 to 20 points (n = 18), 1 year survival was 93.1%, 84.2%, 66.9%, and 27.8%, respectively. The c-index of our score was 0.73 [95% confidence interval (CI): 0.69-0.77]. Values were in our cohort for the US and French scores 0.66 (95% CI: 0.62-0.70) and 0.63 (95% CI: 0.59-0.67), respectively.ConclusionsData indicate that our score, but also risk assessment tools from other transplant regions, may be used as a reliable support for risk-adjusted organ allocation and potentially help to improve outcomes in heart transplantation. Further developments will have to include as yet unaccounted risk factors for even more reliable predictions.

Project description:Background and objectivesThe current allocation algorithm for deceased donor kidney transplantation takes into consideration HLA mismatches at the ABDR loci but not HLA mismatches at other loci, including HLA-DQ. However, the independent effects of incompatibilities for the closely linked HLA-DQ antigens in the context of HLA-DR antigen matched and mismatched allografts are uncertain. We aimed to determine the effect of HLA-DQ mismatches on renal allograft outcomes.Design, setting, participants, & measurementsUsing data from the Australia and New Zealand Dialysis and Transplant Registry, we examined the association between HLA-DQ mismatches and acute rejections in primary live and deceased donor kidney transplant recipients between 2004 and 2012 using adjusted Cox regression models.ResultsOf the 788 recipients followed for a median of 2.8 years (resulting in 2891 person-years), 321 (40.7%) and 467 (59.3%) received zero and one or two HLA-DQ mismatched kidneys, respectively. Compared with recipients who have received zero HLA-DQ mismatched kidneys, those who have received one or two HLA-DQ mismatched kidneys experienced greater numbers of any rejection (50 of 321 versus 117 of 467; P<0.01), late rejections (occurring >6 months post-transplant; 8 of 321 versus 27 of 467; P=0.03), and antibody-mediated rejections (AMRs; 12 of 321 versus 38 of 467; P=0.01). Compared with recipients of zero HLA-DQ mismatched kidneys, the adjusted hazard ratios for any and late rejections in recipients who had received one or two HLA-DQ mismatched kidneys were 1.54 (95% confidence interval [95% CI], 1.08 to 2.19) and 2.85 (95% CI, 1.05 to 7.75), respectively. HLA-DR was an effect modifier between HLA-DQ mismatches and AMR (P value for interaction =0.02), such that the association between HLA-DQ mismatches and AMR was statistically significant in those who have received one or two HLA-DR mismatched kidneys, with adjusted hazard ratio of 2.50 (95% CI, 1.05 to 5.94).ConclusionsHLA-DQ mismatches are associated with acute rejection, independent of HLA-ABDR mismatches and initial immunosuppression. Clinicians should be aware of the potential importance of HLA-DQ matching in the assessment of immunologic risk in kidney transplant recipients.

Dataset Information

Observed elevated donor-derived cell free DNA in orthotopic heart transplant recipients without clinical evidence of rejection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure