Altered expression of type II sodium/phosphate cotransporter in polycystickidney disease

Renal phosphate (Pi) absorption is mediated via the type II sodium/Pi cotra nsporter (NaPi-2) in the brush border membrane (BBM) of proximal tubules. S imultaneous detection of NaPi-2 mRNA by in situ hybridization and of NaPi-2 immunoreactivity by immunohistochemistry was performed to investigate the distribution of the cotransporter in healthy control rats and during progre ssion of autosomal dominant polycystic kidney disease (ADPKD). The purpose of the study was to disclose a relation between proximal tubular cell diffe rentiation and NaPi-2 expression. In controls, NaPi-2 expression was presen t in the entire proximal tubule. In the Han:SPRD (cy/+) model for ADPKD, th e proximal nephron is primarily affected by the cystic changes. Epithelial proliferation and impaired epithelial-matrix interaction result in a loss o f cell differentiation that eventually leads to cystic enlargement of the n ephron. Normal expression of NaPi-2 in this model was found only in tubules with intact BBM. Loss of BBM and cellular interdigitation were paralleled by the loss of NaPi-2 in situ hybridization and immunoreactive signals. The se changes were moderate and focal in 2-mo-old rats and generalized all ove r the cortex after 8 mo. Advanced renal damage in the older PKD group was a ssociated with mild phosphaturia, which suggests functional insufficiency o f tubular NaPi-2 reabsorption. These data show how proliferative changes an d loss of tubular epithelial differentiation in ADPKD may prevent functiona l expression of the NaPi-2 system in the proximal tubule in a rapidly progr essive manner. NaPi-2 in proximal tubule BBM is suggested to play an import ant role in impaired tubular absorption of Pi in renal disease.