The hypothesis that protein metabolites regulate renal growth has been
considered for decades, and the overall objective of this work was to
test this hypothesis in vitro using an established line of renal tubu
lar epithelial cells, NRK-52E. The addition of urea to the medium of c
onfluent cultures stimulated DNA synthesis which was dependent on the
concentration of urea, but independent of the presence of serum. Urea
enhanced proliferation of subconfluent cultures of NRK cells in the pr
esence of dilute serum to a similar degree as epidermal growth factor
(EGF). Either deletion of serum from the medium or allowing the cultur
es to achieve confluence prevented the proliferative response to urea,
but not EGF. Ammonium chloride stimulated the uptake of H-3-thymidine
but did not increase cell number. Ammonium chloride increased the upt
ake of H-3-leucine and total cellular protein/DNA, while urea had no e
ffect on these markers of growth. The rate of hydrolysis of urea to am
monia in vitro was not altered by the presence of NRK cells. These res
ults suggest that urea and ammonia may regulate renal mass, and that t
heir actions are separate and different.