1992 Homer Smith Award. Fluid secretion, cellular proliferation, and the pathogenesis of renal epithelial cysts.

Renal cysts, caused by hereditary or acquired disorders, develop in tubule segments. The central pathogenetic elements of cyst formation include abnormal cellular proliferation, accumulation of intratubular liquid, and remodeling of the extracellular matrix. This review addresses the pathogenetic basis of liquid collection and cellular proliferation. Cavity liquid. At an early stage of growth, most renal cysts become detached from the tubule segment of origin; thus, transepithelial fluid secretion is the source of the liquid in most macroscopic cysts. Evidence from in situ and in vitro studies of intact cysts and epithelium cultured from cyst walls and normal renal tubules indicates that: (1) solutes (NaCl) are secreted into the cysts and water flows secondarily by osmosis; (2) active Na+ transport has a primary or secondary role in the secretion of Na+ and Cl-; and (3) the rate of liquid secretion can be modulated by hormones (arginine vasopressin), autocoids (prostaglandin E1 and E2), growth factors (epidermal growth factor), and unknown factors in cyst fluids. Cellular proliferation. Epithelial cells of renal cysts appear to proliferate more than normal. Each cyst resembles a tumor, except that the mass is composed primarily of liquid rather than cells. The proliferation of cyst epithelial cells is associated with: (1) abnormal expression of proto-oncogenes; (2) abnormal displays of morphologic and biochemical phenotypic markers; and (3) abnormal responsiveness to growth factors. The maturation arrest hypothesis, 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 strategies to control the growth of renal cysts may reasonably target processes that inhibit fluid secretion, maximize fluid absorption, and redifferentiate the immature and abnormally proliferative epithelial cells within cysts.