Ontogeny of renal phosphate transport and the process of growth.

The kidneys of infants and children reabsorb a high fraction of the filtered phosphate (Pi), as appropriate to the needs of a growing organism. This high Pi reabsorptive rate is associated with a high capacity (Vmax) of the Na+-Pi symport system. At the molecular level this high reabsorptive capacity appears to be due to the presence of a growth-specific Na-Pi cotransporter. Several experimental findings support this assumption. Firstly, the expression of NaPi-2 mRNA is, if anything, lower in the renal cortex of young animals than of adult animals. Secondly, polyA RNA obtained from growing animals depleted of NaPi-2 by specific hybridization with an antisense 16-mer induces Na+-Pi transport in oocytes. No induction of Na+-Pi transport was observed in oocytes injected with hybridized polyA RNA obtained from adult animals. Thirdly, polyA RNA derived from young rats, depleted of NaPi-2 by subtractive hybridization with adult animal renal cortical cDNA, retains its ability to encode for Na+-Pi cotransport in oocytes. Adult animal renal cortical polyA RNA, depleted of NaPi-2 by subtractive hybridization, failed to induce Na+-Pi uptake into oocytes. Fourthly, renal cortical polyA RNA from young animals, depleted of NaPi-2, contains a region that is highly homologous (80%-92%) with the corresponding region of other modulated NaPi (type II) transporters. Fifthly, this region is also present in the polyA RNA obtained from the renal cortex of newborn rats (1st week of life), despite the fact that NaPi-2 is absent at this early age. Lastly, Npt2 (-/-) knockout mice, although hypophosphatemic and phosphaturic, filter and reabsorb Pi at rates exceeding those that can be accounted for by the expression of type I and III transporters. Based on these observations it is reasonable to surmise that the high Vmax of the Na+-Pi cotransport system observed in the young is due to a large extent to the presence of a growth-specific NaPi transporter, homologous but not identical to already cloned type II NaPi transporters.