Article ; Online: Combining Blood Gene Expression and Cellfree DNA to Diagnose Subclinical Rejection in Kidney Transplant Recipients.
Clinical journal of the American Society of Nephrology : CJASN
2021 Volume 16, Issue 10, Page(s) 1539–1551
Abstract: 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- ... ...
| Abstract | 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 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 ( 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. |
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| MeSH term(s) | Adult ; Asymptomatic Diseases ; Biomarkers/blood ; Biopsy ; Cell-Free Nucleic Acids/blood ; Cell-Free Nucleic Acids/genetics ; DNA/blood ; DNA/genetics ; Female ; Gene Expression Profiling ; Graft Rejection/blood ; Graft Rejection/diagnosis ; Graft Rejection/genetics ; Graft Rejection/immunology ; Humans ; Kidney Transplantation/adverse effects ; Male ; Middle Aged ; Predictive Value of Tests ; Reproducibility of Results ; Tissue Donors ; Transcriptome ; Treatment Outcome ; United States ; Young Adult | |||||
| Chemical Substances | Biomarkers ; Cell-Free Nucleic Acids ; DNA (9007-49-2) | |||||
| Language | English | |||||
| Publishing date | 2021-10-07 | |||||
| Publishing country | United States | |||||
| Document type | Comparative Study ; Journal Article ; Multicenter Study ; Observational Study ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 2226665-3 | |||||
| ISSN | 1555-905X ; 1555-9041 | |||||
| ISSN (online) | 1555-905X | |||||
| ISSN | 1555-9041 | |||||
| DOI | 10.2215/CJN.05530421 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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