Sunaree Saejong1, Natavudh Townamchai2, Poorichaya Somparn3, Pattarin Tangtanatakul4, Thunnicha Ondee5, Nattiya Hirankarn6, Asada Leelahavanichkul5. 1. Medical Microbiology Interdisciplinary Program, Graduate School, Chulalongkorn University, Bangkok, Thailand. 2. Center of Excellence in Solid Organ Transplantation, Division of Nephrology, Department of Medicine, Chulalongkorn University, Bangkok, Thailand. 3. Center of Excellence in Systems Biology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. 4. Department of Transfusion Medicine and Clinical Microbiology, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand. 5. Translational Research In Inflammation and Immunology Research Unit (TRIRU), Department of Microbiology, Chulalongkorn University, Bangkok, Thailand. 6. Center of Excellence in Immunology and Immune-Mediated Diseases, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Abstract
BACKGROUND: Non-invasive diagnosis of interstitial fibrosis and tubular atrophy (IF/TA), a major cause of chronic allograft dysfunction in post-kidney transplantation (post-KT), is needed. OBJECTIVE: Several candidates of microRNAs (miRs) in plasma exosome or whole plasma were evaluated for IF/TA biomarker. METHODS: Kidney samples from biopsy and plasma were tested for miRs expression. RESULTS: Expression of miR-21, miR-142-3p and miR-221 in renal histology with high fibrosis score (Banff classification) was higher than the samples with lesser score (n = 17/group). However, expression of these miRs from plasma exosome or from whole plasma of post-KT patients with different severity of IF/TA as determined by percentage of IF/TA including; grade I (5-25%) (n = 15), grade II (26-50%) (n = 15), grade III (≥ 50%) (n = 6) versus stable graft function (no IF/TA) (n = 15) was not different. However, high expression of miR-21 in exosome, but not from whole plasma, was demonstrated in IF/TA grade II and III compared with IF/TA grade I. In contrast, serum creatinine (Scr) and proteinuria, the current standard biomarkers, could not differentiate IF/TA grade I out of grade II/III. There was no correlation between exosome miR-21 versus the current standard renal injury biomarkers, including Scr, blood urea nitrogen and proteinuria, in IF/TA grade II or grade III. CONCLUSIONS: High miR-21 in plasma exosome, but not in whole plasma, indicated high grade IF/TA in post-KT patients. This non-invasive monitoring biomarker allows the more frequent evaluation on IF/TA than renal biopsy (a standard but more invasive procedure) resulting in the earlier management. More studies on patients are warrant.
BACKGROUND: Non-invasive diagnosis of interstitial fibrosis and tubular atrophy (IF/TA), a major cause of chronic allograft dysfunction in post-kidney transplantation (post-KT), is needed. OBJECTIVE: Several candidates of microRNAs (miRs) in plasma exosome or whole plasma were evaluated for IF/TA biomarker. METHODS: Kidney samples from biopsy and plasma were tested for miRs expression. RESULTS: Expression of miR-21, miR-142-3p and miR-221 in renal histology with high fibrosis score (Banff classification) was higher than the samples with lesser score (n = 17/group). However, expression of these miRs from plasma exosome or from whole plasma of post-KT patients with different severity of IF/TA as determined by percentage of IF/TA including; grade I (5-25%) (n = 15), grade II (26-50%) (n = 15), grade III (≥ 50%) (n = 6) versus stable graft function (no IF/TA) (n = 15) was not different. However, high expression of miR-21 in exosome, but not from whole plasma, was demonstrated in IF/TA grade II and III compared with IF/TA grade I. In contrast, serum creatinine (Scr) and proteinuria, the current standard biomarkers, could not differentiate IF/TA grade I out of grade II/III. There was no correlation between exosome miR-21 versus the current standard renal injury biomarkers, including Scr, blood urea nitrogen and proteinuria, in IF/TA grade II or grade III. CONCLUSIONS: High miR-21 in plasma exosome, but not in whole plasma, indicated high grade IF/TA in post-KT patients. This non-invasive monitoring biomarker allows the more frequent evaluation on IF/TA than renal biopsy (a standard but more invasive procedure) resulting in the earlier management. More studies on patients are warrant.