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Published on: July 19, 2018
miR-21 Promotes Fibrogenesis in Peritoneal Dialysis
Melisa Lopez-Anton1, Mark Lambie2, Manuel Lopez-Cabrera3
1Wales Kidney Research Unit, Division of Infection and Immunity, School of Medicine, College of Biomedical and Life Sciences, Cardiff University, Cardiff, United Kingdom.
Abstract:
Peritoneal dialysis (PD) is a life-saving form of renal replacement therapy for those with end-stage kidney disease. Mesothelial cells (MCs) line the peritoneal cavity and help define peritoneal response to treatment-associated injury, a major reason for treatment failure. miRNAs are important regulators, but their roles in peritoneal fibrosis are largely unknown. In this study, miR-21 was one of the most abundant miRNAs in primary MCs, and was up-regulated by the profibrotic cytokine transforming growth factor-β1 and in PD effluent-derived MCs exhibiting mesenchymal phenotypic change. Increased miR-21 was found in peritoneal membrane biopsy specimens from PD patients compared to healthy controls (PD biocompatible, 5.86×, P = 0.0001; PD conventional, 7.09×, P < 0.0001, n = 11 per group). In PD effluent from a cohort of 230 patients, miR-21 was higher in those receiving the therapy long-term compared to new starters (n = 230, miR-21 3.26×, P = 0.001) and associated with icodextrin use (R = 0.52; 95% CI, 0.20-0.84), peritonitis count (R = 0.16; 95% CI, 0.03-0.29), and dialysate cytokines. miR-21 down-regulated programmed cell death 4 and programmed cell death 4 protein was decreased in peritoneal membrane biopsy specimens from PD patients compared to healthy controls. New miR-21 targets were identified that may be important during PD fibrogenesis. These data identify miR-21 as an important effector of fibrosis in the peritoneal membrane, and a promising biomarker in the dialysis effluent for membrane change in patients receiving PD.
Insights
MicroRNA-21 (miR-21) is elevated in patients undergoing peritoneal dialysis (PD), indicating its role in peritoneal fibrosis. This finding suggests miR-21 may serve as a biomarker for peritoneal membrane changes during PD therapy.
Area of Science:
- Nephrology
- Molecular Biology
- Biomarker Discovery
Background:
- Peritoneal dialysis (PD) is a critical renal replacement therapy for end-stage kidney disease.
- Mesothelial cells (MCs) are key in peritoneal response to injury, and fibrosis is a major cause of PD failure.
- The role of microRNAs (miRNAs) in PD-associated peritoneal fibrosis remains largely unexplored.
Purpose of the Study:
- To investigate the role of miR-21 in peritoneal fibrosis during PD.
- To determine if miR-21 levels correlate with PD treatment duration and complications.
- To identify potential miR-21 targets involved in fibrogenesis.
Main Methods:
- Quantification of miR-21 in primary MCs and PD effluent.
- Analysis of miR-21 expression in peritoneal membrane biopsies from PD patients and controls.
- Correlation analysis of miR-21 levels with clinical parameters in a large PD patient cohort.
Main Results:
- miR-21 was upregulated in MCs by TGF-β1 and in PD effluent-derived MCs.
- Significantly increased miR-21 levels were observed in peritoneal biopsies from PD patients versus controls.
- Higher miR-21 levels in PD effluent correlated with longer PD therapy duration, icodextrin use, and peritonitis history.
Conclusions:
- miR-21 is a key mediator of peritoneal fibrosis in PD patients.
- miR-21 is a promising biomarker detectable in PD effluent for monitoring peritoneal membrane changes.
- Targeting miR-21 may offer a therapeutic strategy for preventing PD-associated fibrosis.
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