THE PATHOGENESIS OF POLYCYSTIC KIDNEY-DISEASE

Polycystic kidney disease (PKD) is a genetic or acquired disorder char acterized by progressive distention of multiple tubular segments and m anifested by fluid accumulation, growth of non-neoplastic epithelial c ells and remodeling of the extracellular matrix resulting ultimately i n some degree of renal functional impairment, with the potential for r egression following removal of the inductive agent(s). It is due to an aberration of one or more factors regulating tubular morphogenesis. H uman PKD can pursue a rapid course with renal failure occurring perina tally (infantile PKD) or an indolent course without renal failure deve loping during the life of the individual (adult PKD). Human acquired P KD develops in atrophic and scarred end-stage kidneys with non-cystic forms of renal disease. Cell proliferation, fluid secretion, impaired cell-cell and cell-matrix interaction, defective function of the Golgi apparatus, cell undifferentiation, and an abnormal matrix have been i mplicated in the pathogenesis of PKD based on clinical and experimenta l studies. Under normal conditions, the dynamic turnover of tubular ep ithelia and matrices are tightly regulated to maintain tubular morphol ogy. The basic defect in PKD is tubular dysmorphogenesis. Our finding indicates that the principal phenotypic features of autosomal dominant PKD (ADPKD) are altered structure and function of the Golgi complex, altered structure and composition of the matrix and cell undifferentia tion, all of which are probably interrelated. If the gene product of t he ADPKD 1 gene results in a defective matrix, the abnormal Golgi func tion and cell differentiation may be due to faulty matrix-cell communi cation.