Peritoneal Effluent MicroRNA Profile in Encapsulating Peritoneal Sclerosis

Background: Encapsulating peritoneal sclerosis (EPS) is a catastrophic complication of chronic peritoneal dialysis (PD). Late diagnosis is associated with high mortality. With the advancement of new diagnostic technologies, such as microRNA (miRNA), we attempted to develop a noninvasive test to assist in the diagnosis of EPS. Methods: MiRNA expression profiles of PD effluents from patients with or without EPS were examined by a high-throughput real-time PCR array to first screen candidate miRNAs. Candidate miRNAs were verified by single real-time PCR. The model for EPS prediction was evaluated by multiple logistic regression. Finding: We collected eight-hour PD effluents from 71 non-EPS and 56 EPS patients. The screening set included 28 samples (20 of non-EPS vs. 8 of EPS). After analyzing the ratio values of two miRNA expression levels from the PCR-array of 377 miRNAs, eight candidate miRNAs were selected. The prediction model was conducted using 127 samples (71 of non-EPS vs 56 of EPS) to produce an area under the curve (AUC) value of the miRNA classifier. The ratios of the five miRNAs with the top five ROC values were selected to calculate the combined AUC by logistic regression. The AUC value to detect EPS with the five miRNA ratios was 0.8929 with an accuracy of 78.7%. The accuracy of the EPS diagnosis was further improved to 94.1% after considering clinical characteristics (AUC value 0.9931, sensitivity: 100%, specificity: 94.1%). Interpretation: A signature-based model of clinical characteristics and miRNA expression in PD effluents can efficiently detect EPS, thus preventing the catastrophic prognosis. Funding: This work was supported by the following programs: Academia Sinica, Taiwan (BM103010089 and BM104010113 to CC Huang), the Taiwan Department of Health Cancer Research Center of Excellence (DOH101-TD-C-111-005), Ministry of Science and Technology, Taiwan (MOST 109-2628-B-008-001 and MOST 110-2823-8-008- 002), the National Central University-Landseed Hospital United Research Center (NCU-LSH-109-A-004), and Taoyuan Armed Forces General Hospital (TYAFGH-D- 109024). Declaration of Interest: All authors declare no conflict of interest. Ethical Approval: The study protocol was approved by the medical ethics committee of three medical centers in Taiwan (the China Medical University Hospital, CMUH103-REC2-070; the National Chen Kung University Hospital, B-ER-104-069; and the Kaohsiung Chang Gung Memorial Hospital, 100-2661B)