Direct and indirect cost of urea excretion

Urea, the major end product of protein metabolism in mammals, is the most abundant solute in the urine. Urea excretion is thought to result from filtration curtailed by some passive reabsorption along the nephron. This reabsorption is markedly enhanced by vasopressin and slow urinary flow rate (V), the fraction of filtered urea excreted in the urine (FE(urea)) falling from ~60% at high V to only ~20% at low V. In concentrated urine, normal urea excretion can be maintained only if urea filtration is elevated. This can be achieved by increasing plasma urea concentration (P(urea)) and/or GFR. We have shown that both parameters do increase when normal rats are submitted to chronic alterations in the water intake/vasopressin axis within the normal range of physiologic regulation. This situation is very similar to that observed after alterations in protein intake. In both cases 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 common mechanism is proposed to explain the rise in GFR observed in the two situations. In summary, our studies demonstrate that the antidiuretic effects of vasopressin are responsible for a significant elevation of GFR. This GFR adaptation limits the rise in P(urea), a favorable effect because urea is not as harmless as usually thought. However, this hyperfiltration might have deleterious consequences in diseased kidneys.