Understanding pathogenic mechanisms in polycystic kidney disease provides clues for therapy

Purpose of review Polycystic kidney diseases are a group of inherited disorders that result in tubular dilatation and/or the development of fluid-filled cysts in the kidney. Identification and analysis of the primary defective protein in many of these diseases are providing insights into a common pathogenesis to polycystic kidney disease. This review explores this pathogenesis and determines the role that this knowledge is playing in the development of potential therapies. Recent findings Study of simple and syndromic forms of polycystic kidney disease has revealed that the defective proteins are localized to the primary cilia/basal body and that the pleiotropic phenotypes are often associated with defective ciliogenesis. Data indicating that the polycystins are involved in ciliary mechanosensation, and cellular changes in intracellular Ca2+ and cAMP, have provided clues for possible therapeutic approaches that have proved highly effective in pre-clinical trials. Summary Polycystic kidney diseases are associated with defects to proteins involved in developing functional, sensory cilia in the kidney. While the primary defects in these disorders cannot be corrected at present, downsteam cellular changes can be targeted. Potential therapeutic agents are now being tested in patients, moving polycystic kidney disease research into a new and exciting phase.