THE PATHOGENESIS OF MULTICYSTIC DYSPLASTIC KIDNEY-DISEASE - INSIGHTS FROM THE STUDY OF FETAL KIDNEYS

The pathogenesis of multicystic dysplastic kidney disease (MCDKD) is u nknown. Most morphologic studies of MCDKD kidneys have been performed when the kidneys are resected postnatally, when their architecture has been distorted by massive cyst enlargement. We obtained two MCDKD kid neys at an early stage of development (14 and 19 weeks' gestation) and examined the pattern of nephrogenesis in detail. In both affected kid neys, we identified islands of spatially dislocated metanephric blaste ma adjacent to zones containing all the normal structural elements of nephrogenesis, including aggregates of induced mesenchyme, S-shaped bo dies and maturing glomeruli, and proximal and distal tubules. Metaneph ric blastemal cells displayed characteristic vimentin and smooth muscl e actin immunoreactivity and insulin-like growth factor II gene expres sion, whereas induced elements exhibited appropriate cytokeratin immun oreactivity and Wilms' tumor gene expression. In most other zones, ren al cysts were lined with epithelia varying from a flattened squamous t o a cuboidal morphology and expression of markers suggested their orig in to be from all portions of the nephron including Bowman's space, pr oximal tubule, and collecting duct. In some cysts, small clusters of e pithelial cells were identified within the cyst lumen. These studies s uggest that in the early stages of MCDKD, normal nephrogenesis occurs in what seems to be a normal metanephric blastema; however, an intrins ic abnormality in the branching morphogenesis of the ureteric duct mig ht be responsible for the development of the histopathologic changes d escribed.