Author(s): Ye M, Grantham JJ
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Abstract 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 secretion of fluid may account for this accumulation. METHODS: We studied in vitro intact cysts that were excised from kidneys removed from three patients with end-stage autosomal dominant polycystic kidney disease. The 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 correct for the wide variation in the sizes of the cysts. To test for endogenous secretagogues, cyst fluid was added to confluent monolayer cultures of canine- and human-kidney cells. RESULTS: During the first 24 hours of incubation, the mean (+/- SE) rate of fluid secretion in nine cysts containing natural cyst fluid was 20.8 +/- 5.6 microliters per square centimeter of surface area per 24 hours, as compared with 2.3 +/- 3.6 microliters per square centimeter per 24 hours in nine cysts containing incubation medium. Each group of cysts was then incubated with forskolin, a nonspecific stimulator of adenylate cyclase activity, for an additional 24 hours. During this period the fluid-secretion rate of cysts containing natural cyst fluid did not change; however, the secretion rate of those containing incubation medium increased to 9.1 +/- 4.4 microliters per square centimeter per 24 hours (mean change, 6.8 +/- 1.1; P < 0.001). Cyst fluid stimulated fluid secretion by polarized monolayers of canine- and human-kidney cells. CONCLUSIONS: Renal cysts from patients with autosomal dominant polycystic kidney disease can secrete fluid, and net fluid secretion can be increased by unidentified secretagogues in the cyst fluid. These results suggest that the process of cyst enlargement may be susceptible to pharmacologic intervention.
This article was published in N Engl J Med
and referenced in Biochemistry & Physiology: Open Access