Associations of circulating MicroRNAs (miR-21-5p, miR-20a-5p) and chronic allograft nephropathy in renal transplant recipients
Yu-Jen Chen1, Chia-Tien Hsu1, Shang-Feng Tsai1,2,3, Cheng-Hsu Chen1,2,3,4.
1Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 2Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; 3Department of Life Science, Tunghai University, Taichung, Taiwan; 4School of Medicine , China Medical University, Taichung, Taiwan
Introduction: The potent immunosuppressive agents significantly improve renal graft survival, however, maintenance long-term graft survival is the major unmet needs. The 10 years graft survival of kidney transplant (KTx) recipients is around 50-60%. The main etiology of chronic allograft nephropathy (CAN) is the result of immunological and nonimmunological injury. Though kidney biopsy can provide definite diagnosis, it remains an invasive procedure. Image studies, blood/urine biomarkers for diagnosis CAN had been reported in recent years. Serum microRNA (miRNA) is one of the promising tool, however, the role of miRNA in CAN had not been thoroughly studied.
Method: A total of 40 KTx recipients with late renal graft survival for more than 10 years. The control recipients (n = 20) should have GFR ≥ 60 ml/min without proteinuria and hematuria for consecutive 3 months before the study. The recipients with chronic graft dysfunction group (n = 20) will be included biopsy-proved chronic transplant allograft nephropathy/rejection, or their eGFR between 15 to 60 ml/min. We performed RNA sequencing to profile the miRNAs expression to predict the potential targets of differential expressed miRNAs in CAN.
Results: miR-20a-5p was increased in the chronic graft dysfunction group (log 2 ratio: 1.552, p = 0.0132), and miR-21-5p was decreased in the graft dysfunction group (log2 ratio: -0.721, P = 0.0002). The pathway analysis revealed that miR-20a-5p and miR-21-5p was associated with TGF-beta pathway.
Conclusion: It is demonstrated that miR-20a-5p and miR-21-5p were identified as the novel chronic graft dysfunction-associated miRNAs with TGF-beta pathway, which may play critical roles in allograft fibrogenesis. In the future, the further study might help discover these biomarkers or therapeutic tools for enhancing the ability for early prediction and intervention and improving long-term graft survival in KTx.
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