Role of Aquaporin in Long-term Peritoneal Dialysis

Park, M S; Cha, J H; Kim, J; Nielsen, Soren

Abstract

Sufficient fluid removal is vital to renal replacement therapy in end-stage renal failure patients. Aquaporins are integral membrane proteins and the primary water channels that allow water transport only. Type 1, 3 and 4 aquaporins were found in peritoneal capillary walls and peritoneal mesothelial cells. Approximately 5096 of total amount of free water transported during peritoneal dialysis is through aquaporins. Ultrafiltration failure and fluid overload are found in some of long-term continous ambulatory peritoneal dialysis(CAPI3) patients and are major causes of withdrawl from CAPD. Long- term use of high glucose containing dialysis solutions, and functional and morphological changes of aquaporins were suggested as possible mechanisms of ultrafiltration failure. However, a direct relation between alterations of aquaporins in the peritoneum and ultrafiltration failure in long-term CAPD has not been reported yet. In this study peritoneal aquaporins and ultrafiltration were evaluated after long-term peritoneal exposure to high glucose containing dialysis solutions in rats. Sprague-Dawley rats with normal kidney functions were used. Twenty five milliliter of 4.25% glucose containing dialysis solutions were injected into the peritoneal cavity twice a day for 12 weeks in 13 rats(dialysis-group). The other 13 rats were used without intraperitoneal injection as controls (control-group). One rat from each group died during the study was excluded. After 12 weeks of intraperitoneal injection, a 2 hour peritoneal transport study was done in 9 rats from each group. To calculate intraperitoneal fluid absorption rate, (131)I labelled human serum albumin(RISA) was used as a volume marker. Mesenteries were taken from the remaining three rats from each group for immuno-histochemistry for aquaporin type l. Intraperitoneal volume after 2 hour dialysis was significantly lower in dialysis-group than in control-group(33.7+/-3.6 vs 39.4+/-6.1mL, p<0,05). The peri- toneal fluid absorption rate was significamtly higher in dialysis-group than in control-group(0,070+/-0.051 vs 0.049+/-0.016 mL/min, p<0.05). Dg'P>srxlium was signifieantly higher in dialysis-group than in control-group(0.890+/-0.014 vs 0.856+/-0.038, p<0.05).D2/P2urea and D2/D0 glucose did not differ between the two groups. Immunohistochemistry revealed that aquaporin type 1 was strongly stained in the mesentery capillary walls in control-group, while it was almost disappeared in dialysis-group. In conclusion, long-term use of high glucose containing dialysis solutions decreased aquaporin type 1 population in the peritoneum and ultrafiltration volume. Increased peritoneal fluid absorption rate is also in part responsible for decreased ultrafiltration volume after long-term use of dialysie solutions.