#212 The clinical significance of circulating piRNAs in extracellular vesicles in patients with idiopathic membranous nephropathy

Abstract

Abstract Background and Aims Of various small RNAs, many miRNAs have been studied as potential biomarkers for various renal diseases. However, there are few literatures about P-element-induced wimpy testis-interacting RNAs (piRNAs), which are the most recently discovered class of small RNAs. Therefore, we investigated the clinical significance of piRNAs in idiopathic membranous (IMN) patients. Method We prospectively enrolled 60 participants, including those with IMN (n = 19) and idiopathic nephrotic syndrome (INS; n = 21) and healthy volunteers (HVs; n = 20) in this study. Using RNA sequencing, we assessed the serum extracellular vesicle (EV)-piRNA profiles of all participants. We investigated whether the piRNAs could be helpful to discriminate IMN from INS and predict the treatment response of patients with IMN. Based on achievement of clinical remission, IMN patients were divided in to two groups: a well-responding (IMN-W) and refractory (IMN-R) group [IMN-W (n = 9) vs IMN-R (n = 10)]. Results We found 11 piRNAs that were upregulated and 6 that were downregulated in patients with IMN when compared to HVs. There were 22 miRNAs that were upregulated and 23 that were downregulated in patients with IMN when compared to the INS. Among these miRNAs, we found 5 piRNAs, whose levels were significantly up- or downregulated in patients with IMN compared to HVs and patients with INS. There were 50 upregulated and 11 downregulated piRNAs in patients with IMN-R when compared to patients with IMN-W. Of these piRNAs, the expression level of piRNA-42775 and piRNA-36743 were found to be inversely correlated with proteinuria on kidney biopsy. Meanwhile, a positive correlation was observed between renal function and expression of piRNA-43108. Conclusion Patients with IMN have a distinct EV-piRNA expression profile compared with INS and HVs. In addition, circulating EV-piRNAs could be useful to predict the treatment response of IMN patients.