Abstract
BackgroundAcute rejection is hazardous to graft survival in kidney transplant recipients (KTRs). We aimed to identify novel biomarkers for early diagnosis of acute T cell-mediated rejection (TCMR) in urinary exosomes of KTRs.MethodsAmong 458 graft biopsies enrolled in a cross-sectional multicenter study, 22 patients with stable graft function (STA) who had not shown pathologic abnormality and 25 patients who diagnosed biopsy-proven TCMR were analyzed. We performed proteomic analysis using nano-ultra performance liquid chromatography-tandem mass spectrometry (nano-UPLC-MS/MS) to identify candidate biomarkers for early TCMR diagnosis on urinary exosomes. We confirmed the protein levels of each candidate biomarker by western blot analysis.ResultsA total of 169 urinary exosome proteins were identified by nano-UPLC-MS/MS. Forty-six proteins showed increased expression in STA patients, while 17 proteins were increased in TCMR patients. Among them, we selected five proteins as candidate biomarkers for early diagnosis of TCMR according to significance, degree of quantity variance, and information from the ExoCarta database. We confirmed the proteomic expression levels of five candidate biomarkers by western blot analysis in each patient. Of all candidate biomarkers, tetraspanin-1 and hemopexin were significantly higher in TCMR patients (STA:TCMR ratio = 1:1.8, P = 0.009, and 1:3.5, P = 0.046, respectively).ConclusionsTetraspanin-1 and hemopexin were detected in KTR urine and could act as potential diagnostic proteins for TCMR.
Highlights
Kidney transplantation (KT) is the treatment of choice for patients with end-stage renal disease [1]
A total of 169 urinary exosome proteins were identified by nano-UPLC-MS/MS
We selected five proteins as candidate biomarkers for early diagnosis of T cell-mediated rejection (TCMR) according to significance, degree of quantity variance, and information from the ExoCarta database
Summary
Kidney transplantation (KT) is the treatment of choice for patients with end-stage renal disease [1]. The development of more potent and effective immunosuppressive agents has decreased the acute rejection incidence in kidney transplant recipients (KTRs). There is no clear improvement in long-term graft survival [3, 4], and there exists no definitive diagnostic tool to assess this, apart from allograft biopsy [5]. Kidney allograft biopsy, coupled with histopathologic examination, is the gold standard for diagnosing acute rejection in KTRs; there exist several limitations. Diagnosis of acute rejection is important for graft management and improving long-term graft survival; the aforementioned limitations influence the opportunity for early diagnosis. Acute rejection is hazardous to graft survival in kidney transplant recipients (KTRs). We aimed to identify novel biomarkers for early diagnosis of acute T cell-mediated rejection (TCMR) in urinary exosomes of KTRs
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