Urea, the major end product of protein metabolism in mammals, is the m
ost abundant solute in the urine. Urea excretion is thought to result
from filtration curtailed by some passive reabsorbtion along the nephr
on. This reabsorption is markedly enhanced by vasopressin and slow uri
nary flow rate (V), the fraction of filtered urea excreted in the urin
e (FE(urea)) falling from approximate to 60% at high V to only approxi
mate to 20% at low V. In concentrated urine, normal urea excretion can
be maintained only if urea filtration is elevated. This can be achiev
ed by increasing plasma urea concentration (P-urea) and/or GFR. We hav
e shown that both parameters do increase when normal rats are submitte
d to chronic alterations in the water intake/vasopressin axis within t
he normal range of physiologic regulation. This situation is very simi
lar to that observed after alterations in protein intake. In both case
s more urea needs to be filtered, either because more of it has to be
excreted, or because the efficiency of its excretion is reduced. A com
mon mechanism is proposed to explain the rise in GFR observed in the t
wo situations. In summary, our studies demonstrate that the antidiuret
ic effects of vasopressin are responsible for a significant elevation
of GFR. This GFR adaptation limits the rise in P-urea, a favorable eff
ect because urea is not as harmless as usually thought. However, this
hyperfiltration might have deleterious consequences in diseased kidney
s.