FLUID SECRETION, CELLULAR PROLIFERATION, AND THE PATHOGENESIS OF RENAL EPITHELIAL CYSTS

Renal cysts, caused by hereditarY or acquired disorders, develop in tu bule segments. The central pathogenetic elements of cyst formation inc lude ab-normal cellular proliferation, accUMulation of intratubular li quid, and remodeling of the extracellular matrix. This review addresse s the pathogenetic basis of liquid collection and cellular proliferati on. CavitY liquid. At an early stage of growth, most renal cysts becom e detached from the tubule segment of origin; thus, transepithelial fl uid secretion is the source of the liquid in most macroscopic cysts. E vidence from in situ and in vitro studies of intact cysts and epitheli um cultured from cyst walls and normal renal tubules indicates that: ( 1) solutes (NaCl) are secreted into the cysts and water flows secondar ily by osmosis; (2) active Na+ transport has a primary or secondary ro le in the secretion of Na+ and Cl-; and (3) the rate of liquid secreti on can be modulated by hormones (arginine vasopressin), autocoids (pro staglandin E1 and E2), growth factors (epidermal growth factor), and u nknown factors in cyst fluids. Cellular proliferation. Epithelial cell s of renal cysts appear to proliferate more than normal. Each cyst res embles a tumor, except that the mass is composed primarily of liquid r ather than cells. The proliferation of cyst epithelial cells is associ ated with: (1) abnormal expression of proto-oncogenes; (2) abnormal di splays of morphologic and biochemical phenotypic markers; and (3) abno rmal responsiveness to growth factors. The maturation arrest hypothesi s, introduced as a framework to explore the pathogenetic basis of all renal cysts, supposes that the epithelial cells comprising cysts are ' 'locked' in an immature, dedifferentiated state. Therapeutic strategie s to control the growth of renal cysts may reasonably target processes that inhibit fluid secretion, maximize fluid absorption, and rediffer entiate the immature and abnormally proliferative epithelial cells wit hin cysts.