Project description:Background and objectivesData reported to the Organ Procurement and Transplantation Network (OPTN) are used in kidney transplant research, policy development, and assessment of center quality, but the accuracy of early post-transplant outcome measures is unknown.Design, setting, participants, & measurementsThe Deceased Donor Study (DDS) is a prospective cohort study at five transplant centers. Research coordinators manually abstracted data from electronic records for 557 adults who underwent deceased donor kidney transplantation between April of 2010 and November of 2013. We compared the post-transplant outcomes of delayed graft function (DGF; defined as dialysis in the first post-transplant week), acute rejection, and post-transplant serum creatinine reported to the OPTN with data collected for the DDS.ResultsMedian kidney donor risk index was 1.22 (interquartile range [IQR], 0.97-1.53). Median recipient age was 55 (IQR, 46-63) years old, 63% were men, and 47% were black; 93% had received dialysis before transplant. Using DDS data as the gold standard, we found that pretransplant dialysis was not reported to the OPTN in only 11 (2%) instances. DGF in OPTN data had a sensitivity of 89% (95% confidence interval [95% CI], 84% to 93%) and specificity of 98% (95% CI, 96% to 99%). Surprisingly, the OPTN data accurately identified acute allograft rejection in only 20 of 47 instances (n=488; sensitivity of 43%; 95% CI, 17% to 73%). Across participating centers, sensitivity of acute rejection varied widely from 23% to 100%, whereas specificity was uniformly high (92%-100%). Six-month serum creatinine values in DDS and OPTN data had high concordance (n=490; Lin concordance correlation =0.90; 95% CI, 0.88 to 0.92).ConclusionsOPTN outcomes for recipients of deceased donor kidney transplants have high validity for DGF and 6-month allograft function but lack sensitivity in detecting rejection. Future studies using OPTN data may consider focusing on allograft function at 6 months as a useful outcome.

Project description:Background and objectives: This report describes an unusual presentation of severe hypertension (HTN) in a subset of pediatric kidney recipients treated with a steroid avoidance pediatric renal transplantation protocol. The HTN was secondary to atypical, reno-vascular abnormalities (RVA) of the transplanted vasculature, temporally associated with erythropoietin (EPO) use. Design, setting, participants, and measurements: To investigate the clinical significance underlying this event, a retrospective clinical study of 100 pediatric renal transplants was undertaken (50 steroid-free and 50 matched steroid-based controls), with peripheral blood transcriptional analysis of four RVA patients and controls. Results: Regardless of a higher observed incidence of anemia (p < 0.001) and greater overall EPO usage in the first post-transplant year in steroid-free patients, the incidence of new-onset HTN at one yr was significantly less in the steroid-free cohort (p = 0.03). Nevertheless, early EPO (first week post-transplant) was significantly associated with the combinatory findings of new-onset HTN (p = 0.03) and RVA (p = 0.007). Molecular mechanisms of RVA injury were investigated further by peripheral blood cDNA microarray gene expression profiling. A panel of 42 transcripts differentiated patients with RVA and HTN from three sets of matched controls, with and without HTN and EPO use, with 100% concordance (p < 0.001). The biological processes governed by these significant genes suggest a role for EPO regulation of growth factor receptor ubiquitination as a putative mechanism for renal vascular injury. Conclusion: This study cautions against the use early post-transplant use of EPO in immunosuppression regimens with steroid minimization/avoidance, which may have an increased incidence of post-transplant anemia. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Disease State: patient with high blood pressure Keywords: Logical Set Using regression correlation

Project description:Background and objectives: This report describes an unusual presentation of severe hypertension (HTN) in a subset of pediatric kidney recipients treated with a steroid avoidance pediatric renal transplantation protocol. The HTN was secondary to atypical, reno-vascular abnormalities (RVA) of the transplanted vasculature, temporally associated with erythropoietin (EPO) use. Design, setting, participants, and measurements: To investigate the clinical significance underlying this event, a retrospective clinical study of 100 pediatric renal transplants was undertaken (50 steroid-free and 50 matched steroid-based controls), with peripheral blood transcriptional analysis of four RVA patients and controls. Results: Regardless of a higher observed incidence of anemia (p < 0.001) and greater overall EPO usage in the first post-transplant year in steroid-free patients, the incidence of new-onset HTN at one yr was significantly less in the steroid-free cohort (p = 0.03). Nevertheless, early EPO (first week post-transplant) was significantly associated with the combinatory findings of new-onset HTN (p = 0.03) and RVA (p = 0.007). Molecular mechanisms of RVA injury were investigated further by peripheral blood cDNA microarray gene expression profiling. A panel of 42 transcripts differentiated patients with RVA and HTN from three sets of matched controls, with and without HTN and EPO use, with 100% concordance (p < 0.001). The biological processes governed by these significant genes suggest a role for EPO regulation of growth factor receptor ubiquitination as a putative mechanism for renal vascular injury. Conclusion: This study cautions against the use early post-transplant use of EPO in immunosuppression regimens with steroid minimization/avoidance, which may have an increased incidence of post-transplant anemia. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Disease State: patient with high blood pressure Keywords: Logical Set

Project description:Histologic diagnosis of T cell-mediated rejection in kidney transplant biopsies has limited reproducibility because it is based on non-specific lesions using arbitrary rules that are subject to differing interpretations. We used microarray results from 403 indication biopsies previously given histologic diagnoses to develop a molecular classifier that assigned a molecular T cell-mediated rejection score to each biopsy. Independent assessment of the biopsies by multiple pathologists confirmed considerable disagreement on the presence of TCMR features: 79-88% accuracy and 35-69% sensitivity. The agreement of the molecular T cell-mediated rejection score with the histology diagnosis was similar to agreement among individual pathologists: accuracy 89%, sensitivity 51%. However, the score also predicted the consensus among pathologists, being highest when all agreed. Many discrepancies between the scores and the histologic diagnoses were in situations where histology is unreliable e.g. scarred biopsies. The score correlated with histologic lesions and gene sets associated with T cell-mediated rejection. The transcripts most often selected by the classifier were expressed in effector T cells, dendritic cells, or macrophages or inducible by interferon-gamma. Thus the T cell-mediated rejection score offers an objective assessment of kidney transplant biopsies, predicting the consensus opinion among multiple pathologists, and offering insights into underlying disease mechanisms. Antibody-mediated rejection is a major cause of kidney transplant failure, but the current diagnostic system misses most cases due to dependency on subjective non-standardized tests. We hypothesized that molecular features could provide a test to address this problem. We classified 403 biopsies by a reference standard based on microcirculation lesions and donor-specific HLA antibody, and used microarray analysis to develop a classifier that assigned each biopsy a score reflecting the probability of antibody-mediated rejection. The scores correlated with donor-specific antibody and histologic lesions: 42/45 biopsies with antibody-mediated rejection scores >0.5 had both donor-specific antibody and microcirculation lesions. Intermediate scores (0.2-0.5) were more ambiguous, but became more specific combined with donor-specific antibody. Compared to diagnoses based on histology-plus-donor-specific antibody, the scores had sensitivity 0.67; specificity 0.90. Donor-specific antibody improved the specificity to 0.97. The score correlated not only with diagnoses of individual pathologists but with the consensus among multiple pathologists. The classifier used transcripts expressed in endothelial cells (e.g. CDH13, DARC, ROBO4) and NK cells (e.g. CX3CR1, FGFBP2), as well as IFNG-inducible transcripts e.g. CXCL11. Thus the molecular phenotype of antibody-mediated rejection provides not only an objective test that predicts microcirculation lesions and donor-specific HLA antibody, but also offers mechanistic insights.

Dataset Information

Transplant Onconephrology in Patients With Kidney Transplants.

Publications

Transplant Onconephrology in Patients With Kidney Transplants.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets