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Volume Stress-Induced Peritoneal Endothelin-1 Release in Continuous Ambulatory Peritoneal Dialysis

STANISLAO MORGERA^*, SIMONE KUCHINKE^*, KLEMENS BUDDE^*, ANDREAS LUN, BERTHOLD HOCHER^* and HANS-HELLMUT NEUMAYER^*

^* Department of Nephrology, Charité, Humboldt University of Berlin, Berlin, Germany
Department of Laboratory Medicine and Pathobiochemistry, Charité, Humboldt University of Berlin, Berlin, Germany.

Correspondence to Dr. Stanislao Morgera, Abteilung für Nephrologie, Universitätsklinikum Charité der Humboldt Universität zu Berlin, Schumannstrasse 20-21, 10098 Berlin, Germany. Phone: +49 30 2802 5979; Fax: +49 30 2802 8471; E-mail: stanislao.morgera{at}rz.hu-berlin.de

Abstract. In long-term peritoneal dialysis, functional deterioration of the peritoneal membrane is often associated with proliferative processes of the involved tissues leading to peritoneal fibrosis. In continuous ambulatory peritoneal dialysis (CAPD), failure to achieve target values for adequacy of dialysis is commonly corrected by increasing dwell volume; in case of ultrafiltration failure, osmolarity of the dialysate gets increased. In a prospective study, the impact of increasing dwell volume from 1500 ml to 2500 ml per dwell (volume trial) or changing the osmolarity of the dialysate from 1.36 to 3.86% glucose (hyperosmolarity trial) on the peritoneal endothelin-1 (ET-1) release was analyzed. ET-1 is known to exert significant proliferative activities on a variety of cell types leading to an accumulation of extracellular matrix. A highly significant difference in the cumulative peritoneal ET-1 synthesis was found between the low- and high-volume exchange, whereas differences in the hyperosmolarity setting were only moderate. Sixty minutes after initiating dialysis, the cumulative ET-1 synthesis was 2367 ± 1023 fmol for the 1500 ml versus 6062 ± 1419 fmol for the 2500 dwell (P < 0.0001) and 4572 ± 969 fmol versus 6124 ± 1473 fmol for the 1.36 and 3.86% glucose dwell (P < 0.05), respectively. In conclusion, increasing dwell volume leads to a strong activation of the peritoneal paracrine endothelin system. Because ET-1, apart from being a potent vasoactive peptide, contributes to fibrotic remodeling, this study indicates that volume stress-induced ET-1 release might contribute to structural alteration of the peritoneal membrane in long-term peritoneal dialysis.

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673