Journal of the American Society of Nephrology, Vol 4, 1091-1103, Copyright © 1993 by American Society of Nephrology

EDITORIALS

Is the process of urinary urea concentration responsible for a high glomerular filtration rate?

L Bankir, M Ahloulay, N Bouby, MM Trinh-Trang-Tan, F Machet, B Lacour and P Jungers

For subjects on a normal diet, urea is the major urinary solute and is markedly concentrated in the urine compared with in the plasma. Because urea is not known to undergo active secretion, its excretion rests on filtration lessened to a variable extent by tubular reabsorption. It is well established that the efficiency of urea excretion drops with increasing urinary concentration and decreasing urinary flow rate (from approximately 60% of filtered load, above 2 mL/min, to approximately 20% below 0.5 mL/min) because the prolonged transit time in the distal nephron favors passive urea reabsorption. Thus, a higher urinary concentration is achieved at the expense of a reduced efficiency of urea excretion. Recent experimental observations suggest that GFR could actually increase in parallel with the urinary concentrating activity, thus ensuring a normal urea excretion in the face of a high, concentration-dependent urea reabsorption, with only a moderate increase in plasma urea. A possible mechanism is proposed that could explain how the vasopressin-induced intrarenal recycling of urea (which contributes to improvement in urinary concentration), but not an exogenous urea administration, could indirectly depress the tubuloglomerular feedback and hence increase GFR. An increased concentration of an osmotically active 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 the hyperfiltration seen in various pathophysiologic situations such as chronic vasopressin infusion, high protein intake, severe burns, and diabetes mellitus. Whatever the mechanism, if the need to excrete relatively high amounts of urea in a concentrated urine leads to a sustained 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 sodium reabsorption providing the "single effect" for the urinary concentrating process. It also includes the consequences on the glomerular filter of sustained high pressure and flow and the energy spent in reabsorbing the extra load of solutes filtered. In chronic renal failure, the ability to form hypertonic urine declines but is nevertheless well preserved with respect to declining GFR, thus imposing on remnant nephrons an additional permanent stimulus for hyperfiltration.(ABSTRACT TRUNCATED AT 400 WORDS)

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