DEREGULATION OF CELL-SURVIVAL IN CYSTIC AND DYSPLASTIC RENAL DEVELOPMENT

Various aberrations of cell biology have been reported in polycystic k idney diseases and in cystic renal dysplasias. A common theme in these disorders is failure of maturation of renal cells which superficially resemble embryonic tissue. Apoptosis is a feature of normal murine ne phrogenesis, where it has been implicated in morphogenesis, and fulmin ant apoptosis occurs in the small, cystic kidneys which develop in mic e with null mutations of bcl-2. Therefore, we examined the location an d extent of apoptosis in pre- and postnatal samples of human polycysti c and dysplastic kidney diseases using propidium iodide staining, in s itu end-labeling and electron microscopy. In dysplastic kidneys cell d eath was prominent in undifferentiated cells around dysplastic tubules and was occasionally found in cystic epithelia. The incidence of apop tosis was significantly greater than in normal controls of comparable age both pre- and postnatally. In the polycystic kidneys there was wid espread apoptosis in the interstitium around undilated tubules distant from cysts, in undilated tubules between cysts and in cystic epitheli a. The level of apoptosis compared to controls was significantly incre ased postnatally. A similar increase of cell death was also noted in t he early and late stages of renal disease in the polycystic cpk/cpk mo use model. We speculate that deregulation of cell survival in these ki dneys may reflect incomplete tissue maturation, and may contribute to the progressive destruction of functional kidney tissue in polycystic kidneys and the spontaneous involution reported in cystic dysplastic k idneys.