Combining Blood Gene Expression and Cellfree DNA to Diagnose Subclinical Rejection in Kidney Transplant Recipients
| Autor: | Christopher L. Marsh, John Holman, Michael Abecassis, Steve Kleiboeker, Sunil M. Kurian, Christabel Rebello, Susan S Brietigam, Lihui Zhao, Sookhyeon Park, David J. Taber, Emilio D. Poggio, John J. Friedewald, Kexin Guo, Juston C Weems, Raymond L. Heilman, Rohita Sinha |
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| Rok vydání: | 2021 |
| Předmět: |
Oncology
Transplantation medicine.medical_specialty Receiver operating characteristic Epidemiology business.industry Critical Care and Intensive Care Medicine Logistic regression medicine.disease Kidney transplant Clinical trial Nephrology Internal medicine Gene expression Post-hoc analysis medicine business Kidney transplantation Subclinical infection |
| Zdroj: | Clinical Journal of the American Society of Nephrology. 16:1539-1551 |
| ISSN: | 1555-905X 1555-9041 |
| Popis: | Background and objectives Subclinical acute rejection is associated with poor outcomes in kidney transplant recipients. As an alternative to surveillance biopsies, noninvasive screening has been established with a blood gene expression profile. Donor-derived cellfree DNA (cfDNA) has been used to detect rejection in patients with allograft dysfunction but not tested extensively in stable patients. We hypothesized that we could complement noninvasive diagnostic performance for subclinical rejection by combining a donor-derived cfDNA and a gene expression profile assay. Design, setting, participants, & measurements We performed a post hoc analysis of simultaneous blood gene expression profile and donor-derived cfDNA assays in 428 samples paired with surveillance biopsies from 208 subjects enrolled in an observational clinical trial (Clinical Trials in Organ Transplantation-08). Assay results were analyzed as binary variables, and then, their continuous scores were combined using logistic regression. The performance of each assay alone and in combination was compared. Results For diagnosing subclinical rejection, the gene expression profile demonstrated a negative predictive value of 82%, a positive predictive value of 47%, a balanced accuracy of 64%, and an area under the receiver operating curve of 0.75. The donor-derived cfDNA assay showed similar negative predictive value (84%), positive predictive value (56%), balanced accuracy (68%), and area under the receiver operating curve (0.72). When both assays were negative, negative predictive value increased to 88%. When both assays were positive, positive predictive value increased to 81%. Combining assays using multivariable logistic regression, area under the receiver operating curve was 0.81, significantly higher than the gene expression profile (P Conclusions A combination of blood-based biomarkers can improve detection and provide less invasive monitoring for subclinical rejection. In this study, the gene expression profile detected more cellular rejection, whereas donor-derived cfDNA detected more antibody-mediated rejection. |
| Databáze: | OpenAIRE |
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