CELL POLARITY IN HUMAN RENAL CYSTIC-DISEASE

BACKGROUND: In polycystic kidney disease (PKD), altered cellular polar ity with mislocation of Na/K-ATPase, and net fluid secretion may have a role in cyst development and progression. EXPERIMENTAL DESIGN: Cell polarity was assessed in surgically excised human normal, autosomal do minant PKD, and acquired PKD occurring in end stage renal disease on l ong-term dialysis kidneys quick frozen (<5 minutes) or fixed to minimi ze ischemic changes. RESULTS: Findings were similar in autosomal domin ant PKD and acquired PKD kidneys. By ultrastructure, in cysts, cells w ere polarized, however, their basement membranes were greatly thickene d and reticulated. By immunohistology, in cell-lining cysts, Na/K-ATPa se, fodrin, and ankyrin were localized primarily to basolateral cell m embranes and uvomorulin was localized to lateral cell membranes. In ab out 25% of the cells, however, Na/K-ATPase was localized to the apical as well as the basolateral membranes. Both in autosomal dominant PKD and normal kidney cell monolayers in vitro, cationic ferritin was norm ally absorbed by apical endocytosis, and transferred to apical vacuole s and phagolysosomes. CONCLUSIONS: These findings indicate intact stru ctural and functional polarity in cell-lining cysts; however, in about 25% of the cells, Na/K-ATPase, fodrin, and ankyrin are localized to a pical and lateral cell membranes, probably due to cell dedifferentiati on. The notable changes in the basement membranes of cysts suggest a k ey role for the extracellular matrix in the pathogenesis of PKD.