IS THE PROCESS OF URINARY UREA CONCENTRATION RESPONSIBLE FOR A HIGH GLOMERULAR-FILTRATION RATE

For subjects on a normal diet, urea is the major urinary solute and is markedly concentrated in the urine compared with in the plasma. Becau se urea is not known to undergo active secretion, its excretion rests on filtration lessened to a variable extent by tubular reabsorption. I t is well established that the efficiency of urea excretion drops with increasing urinary concentration and decreasing urinary flow rate (fr om almost-equal-to 60% of filtered load, above 2 mL/min, to almost-equ al-to 20% below 0.5 mL/min) because the prolonged transit time in the distal nephron favors passive urea reabsorption. Thus, a higher urinar y concentration is achieved at the expense of a reduced efficiency of urea excretion. Recent experimental observations suggest that GFR coul d actually increase in parallel with the urinary concentrating activit y, thus ensuring a normal urea excretion in the face of a high, concen tration-dependent urea reabsorption, with only a moderate increase in plasma urea. A possible mechanism is proposed that could explain how t he vasopressin-induced intrarenal recycling of urea (which contributes to improvement in urinary concentration), but not an exogenous urea a dministration, could indirectly depress the tubuloglomerular feedback and hence increase GFR. An increased concentration of an osmotically a ctive solute in the thick ascending limb of Henle's loop (such as urea and, in some cases, glucose) could enable a lower NaCl concentration to be achieved at the macula densa by reducing the osmotically driven water leakage in this nephron segment. This mechanism could explain th e hyperfiltration seen in various pathophysiologic situations such as chronic vasopressin infusion, high protein intake, severe burns, and d iabetes mellitus. Whatever the mechanism, if the need to excrete relat ively high amounts of urea in a concentrated urine leads to a sustaine d elevation of GFR, the price to pay for this water economy is higher than generally assumed. It is not limited to the energy spent in the s odium reabsorption providing the ''single effect'' for the urinary con centrating process. It also includes the consequences on the glomerula r filter of sustained high pressure and flow and the energy spent in r eabsorbing the extra load of solutes filtered. In chronic renal failur e, the ability to form hypertonic urine declines but is nevertheless w ell preserved with respect to declining GFR, thus imposing on remnant nephrons an additional permanent stimulus for hyperfiltration. Accordi ngly, a chronic reduction in urine-concentrating activity, increasing the efficiency of urea excretion, could be expected to slow the progre ssion of chronic renal failure by reducing one of the stimuli of hyper filtration (as has been shown to be the case in 5/6 nephrectomized rat s).