Thus, kidney grafts are prone to losing their function gradually due to kidney graft injury (KGI). Moreover, drug-induced kidney injury by immunosuppressants, chronic ischemic organ damage due to arterial disease, and original disease of the kidney can occur. The kidney transplant is becoming increasingly successful worldwide and in Japan however, kidney grafts can be affected by ischemic reperfusion injury due to transplantation, and the effect of allograft rejection cannot be completely eliminated. KGIs could be diagnosed with urinary EV mRNA analysis with relatively high accuracy. In interstitial fibrosis and tubular atrophy (IFTA) urine samples and those with high Banff chronicity score sums (BChS), POTEM levels may reflect disease severity, and diagnostic formulas using POTEM detected IFTA (AUC 0.830) and high BChS (AUC 0.850). EV B4GALT1 and SPNS2 were also elevated in cABMR, and a diagnostic formula using these markers was able to distinguish between cABMR and chronic calcineurin toxicity accurately (AUC 0.886). A diagnostic formula developed through Sparse Logistic Regression analysis using EV RNA markers allowed us to accurately (with an area under the receiver operator characteristic curve of 0.875) distinguish cABMR from other KGI samples. ResultsĮV CXCL9, CXCL10, and UMOD were elevated in T-cell-mediated rejection samples compared with other KGI samples, while SPNS2 was elevated in chronic antibody-mediated rejection (cABMR) samples. Diagnostic performance of EV RNA markers and diagnostic formulas comprising these markers were evaluated by comparison with the corresponding pathological diagnoses. EVs were isolated from urine samples, and EV RNA markers were assayed using quantitative reverse transcription polymerase chain reaction. One hundred and twenty-seven kidney recipients at 11 Japanese institutions were enrolled in this study urine samples were obtained prior to protocol/episode biopsies. We screened diagnostic biomarkers for KGIs following kidney transplantation using extracellular vesicles (EVs exosomes and microvesicles) from the urine samples of patients. Non-invasive, prompt, and proper detection tools for kidney graft injuries (KGIs) are awaited to ensure graft longevity.
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