Aliskiren prevents the toxic effects of peritoneal dialysis fluids during chronic dialysis in rats.

Abstract

The benefits of long-term peritoneal dialysis (PD) in patients with end-stage renal failure are short-lived due to structural and functional changes in the peritoneal membrane. In this report, we provide evidence for the in vitro and in vivo participation of the renin-angiotensin-aldosterone system (RAAS) in the signaling pathway leading to peritoneal fibrosis during PD. Exposure to high-glucose PD fluids (PDFs) increases damage and fibrosis markers in both isolated rat peritoneal mesothelial cells and in the peritoneum of rats after chronic dialysis. In both cases, the addition of the RAAS inhibitor aliskiren markedly improved damage and fibrosis markers, and prevented functional modifications in the peritoneal transport, as measured by the peritoneal equilibrium test. These data suggest that inhibition of the RAAS may be a novel way to improve the efficacy of PD by preventing inflammation and fibrosis following peritoneal exposure to high-glucose PDFs.

• Authors: Juan Pérez-Martínez, Francisco C Pérez-Martínez, Blanca Carrión, Jesús Masiá, Agustín Ortega, Esther Simarro, Syong H Nam-Cha, Valentín Ceña
• Journal: PloS one (PLoS One) Vol. 7 Issue 4 Pg. e36268 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 22558414 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amides
• Biomarkers
• Fumarates
• aliskiren
• Glucose

Topics

• Amides (pharmacology, therapeutic use)
• Animals
• Biological Transport (drug effects)
• Biomarkers (metabolism)
• Cytoprotection (drug effects)
• Dose-Response Relationship, Drug
• Epithelial Cells (drug effects, metabolism)
• Fibrosis
• Fumarates (pharmacology, therapeutic use)
• Glucose (adverse effects)
• Inflammation (chemically induced, drug therapy)
• Male
• Peritoneal Dialysis (adverse effects)
• Peritoneum (drug effects, pathology)
• Rats
• Rats, Sprague-Dawley
• Renin-Angiotensin System (drug effects)
• Time Factors