Volume stress-induced peritoneal endothelin-1 release in continuous ambulatory peritoneal dialysis

In long-term peritoneal dialysis, functional deterioration of the peritonea l membrane is often associated with proliferative processes of the involved tissues leading to peritoneal fibrosis. In continuous ambulatory peritonea l dialysis (CAPD), failure to achieve target values for adequacy of dialysi s is commonly corrected by increasing dwell volume; in case of ultrafiltrat ion failure, osmolarity of the dialysate gets increased. In a prospective s tudy, the impact of increasing dwell volume from 1500 mi to 2500 mi per dwe ll (volume trial) or changing the osmolarity of the dialysate from 1.36 to 3.86% glucose (hyperosmolarity trial) on the peritoneal endothelin-l (ET-1) release was analyzed. ET-1 is known to exert significant proliferative act ivities on a variety of cell types leading to an accumulation of extracellu lar matrix. A highly significant difference in the cumulative peritoneal ET -I synthesis was found between the low- and high-volume exchange, whereas d ifferences in the hyperosmolarity setting were only moderate. Sixty minutes after initiating dialysis, the cumulative ET-1 synthesis was 2367 +/- 1023 fmol for the 1500 mi versus 6062 +/- 1419 fmol for the 2500 dwell (P < 0.0 001) 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 vo lume leads to a strong activation of the peritoneal paracrine endothelin sy stem. Because ET-1, apart from being a potent vasoactive peptide, contribut es to fibrotic remodeling, this study indicates that volume stress-induced ET-1 release might contribute to structural alteration of the peritoneal me mbrane in long-term peritoneal dialysis.