MicroRNA-21 in plasma exosome, but not from whole plasma, as a biomarker for the severe interstitial fibrosis and tubular atrophy (IF/TA) in post-renal transplantation

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. Conclusion: 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.

Automated summary

This study evaluated microRNA biomarkers for the non-invasive diagnosis of interstitial fibrosis and tubular atrophy (IF/TA) in post-kidney transplantation patients with chronic allograft dysfunction. The results showed that high expression of miR-21 in plasma exosome was associated with the severity of IF/TA. This non-invasive biomarker allows for more frequent evaluation of IF/TA and earlier management.