Proximal tubular cysts in fetal human autosomal recessive polycystic kidney disease

Standard texts describe human autosomal recessive polycystic kidney disease (ARPKD) as a cystic kidney disease in which lesions are localized to colle cting tubules. Murine models of ARPKD consistently demonstrate an early pha se of proximal tubular (PT) cystic involvement, which disappears shortly af ter birth. This is followed by a phase of collecting tubular (CT) cyst form ation and progressive enlargement leading to compromise of renal function a nd death. Because the description of cystic lesions in human ARPKD has been largely based on postnatal specimens, PT cyst formation was hypothesized t o be a characteristic feature of fetal human, as well as murine, ARPKD. Thi s study examines nephron segment-specific cyst localization histochemically by lectin binding in 11 human ARPKD specimens obtained at different fetal and postnatal ages. PT cysts were found in human fetal specimens from gesta tional age 14 wk to 26 wk. The percentage of cysts involving PT segments ra nged from 2 to 31%. The cystic index of PT cysts ranged from 2 to 5. In all specimens in which PT cysts were found, both the percentage of CT cysts an d their cystic index were equal to or greater than the percentage of PT cys ts and the associated PT cystic index. PT cysts were absent in all kidney s pecimens older than 34 wk gestational age. It is concluded that human ARPKD , like murine ARPKD, has a transient phase of PT cyst formation during earl y fetal development.