Integrated Kidney Exosome Analysis for the Detection of Kidney Transplant Rejection

• Published in: ACS nano 2017-11, Vol.11 (11), p.11041-11046
• Main Authors: Park, Jongmin, Lin, Hsing-Ying, Assaker, Jean Pierre, Jeong, Sangmoo, Huang, Chen-Han, Kurdi, Ahmed, Lee, Kyungheon, Fraser, Kyle, Min, Changwook, Eskandari, Siawosh, Routray, Sujit, Tannous, Bakhos, Abdi, Reza, Riella, Leonardo, Chandraker, Anil, Castro, Cesar M, Weissleder, Ralph, Lee, Hakho, Azzi, Jamil R
• Format: Article
• Language: English
• Subjects: Biosensing Techniques - methods; Exosomes - immunology; Extracellular Vesicles - immunology; Extracellular Vesicles - pathology; Female; Graft Rejection - immunology; Graft Rejection - physiopathology; Graft Rejection - urine; Humans; Inflammation - immunology; Inflammation - physiopathology; Inflammation - urine; Kidney - immunology; Kidney - pathology; Kidney Transplantation - adverse effects; Male; Proteomics - methods; T-Lymphocytes - immunology
• ISSN: 1936-0851; 1936-086X
• DOI: 10.1021/acsnano.7b05083

Kidney transplant patients require life-long surveillance to detect allograft rejection. Repeated biopsy, albeit the clinical gold standard, is an invasive procedure with the risk of complications and comparatively high cost. Conversely, serum creatinine or urinary proteins are noninvasive alternatives but are late markers with low specificity. We report a urine-based platform to detect kidney transplant rejection. Termed iKEA (integrated kidney exosome analysis), the approach detects extracellular vesicles (EVs) released by immune cells into urine; we reasoned that T cells, attacking kidney allografts, would shed EVs, which in turn can be used as a surrogate marker for inflammation. We optimized iKEA to detect T-cell-derived EVs and implemented a portable sensing system. When applied to clinical urine samples, iKEA revealed high level of CD3-positive EVs in kidney rejection patients and achieved high detection accuracy (91.1%). Fast, noninvasive, and cost-effective, iKEA could offer new opportunities in managing transplant recipients, perhaps even in a home setting.