SUMMARY Renal cysts are central pathological features in a number of human congenital and acquired diseases, and produce significant morbidity and mortality. This review describes our laboratory’s efforts to identify specific alterations in epithelial cell polarity and differentiation associated with renal tubular cyst formation and progressive enlargement. Studies in a murine model of human autosomal recessive polycystic kidney disease, the C57BL/6J cpk/cpk (CPK) mouse have demonstrated quantitative (increased activity) and qualitative (apical membrane distribution) alterations in Na+,K+-adenosine triphosphatase activity that mediate tubular cyst formation. Proximal tubular cyst formation in CPK kidneys is characterized by increased activity of a basolateral Na+,K+-ATPase, which drives organic anion secretion and consequent tubular fluid secretion. In contrast, collecting tubule cyst formation is characterized by increased apical membrane Na+,K+-ATPase expression, which may be a marker of the relatively undifferentiated phenotype of cyst lining cells. If such apically expressed enzyme is active, it may have pathogenic import in collecting tubule cyst formation and enlargement by mediating net basal to apical vectorial solute and fluid transport.
