THE SECRETION OF FLUID BY RENAL CYSTS FROM PATIENTS WITH AUTOSOMAL-DOMINANT POLYCYSTIC KIDNEY-DISEASE

Background. The mechanism by which fluid accumulates in renal cysts of adults with autosomal dominant polycystic kidney disease is not known . This study was designed to determine whether transepithelial secreti on of fluid may account for this accumulation. Methods. We studied in vitro intact cysts that were excised from kidneys removed from three p atients with end-stage autosomal dominant polycystic kidney disease. T he cysts were loaded with natural cyst fluid or with a combination of Dulbecco's modified Eagle's medium and Ham's F12 medium (DME-F12) and incubated in DME-F12 for 24 hours. Fluid secretion, determined by the change in the weight of the cysts, was expressed as the rate of fluid secretion per square centimeter of surface area per 24 hours, to corre ct for the wide variation in the sizes of the cysts. To test for endog enous secretagogues, cyst fluid was added to confluent monolayer cultu res of canine- and human-kidney cells. Results. During the first 24 ho urs of incubation, the mean (+/-SE) rate of fluid secretion in nine cy sts containing natural cyst fluid was 20.8+/-5.6 mul per square centim eter of surface area per 24 hours, as compared with 2.3+/-3.6 mul per square centimeter per 24 hours in nine cysts containing incubation med ium. Each group of cysts was then incubated with forskolin, a nonspeci fic stimulator of adenylate cyclase activity, for an additional 24 hou rs. During this period the fluid-secretion rate of cysts containing na tural cyst fluid did not change; however, the secretion rate of those containing incubation medium increased to 9.1+/-4.4 mul per square cen timeter per 24 hours (mean change, 6.8+/-1.1; P<0.001). Cyst fluid sti mulated fluid secretion by polarized monolayers of canine- and human-k idney cells. Conclusions. Renal cysts from patients with autosomal dom inant polycystic kidney disease can secrete fluid, and net fluid secre tion can be increased by unidentified secretagogues in the cyst fluid. These results suggest that the process of cyst enlargement may be sus ceptible to pharmacologic intervention.