DIRECT AND INDIRECT COST OF UREA EXCRETION

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.