Renal Functional Reserve - Its Significance In Normal and Salt Depletion Conditions

The aim of this study was the evaluation, in healthy subjects, of the renal functional reserve (RFR). that is, the GFR increase induced by a combined infusion of amino acids (AA) and dopamine (D), in conditions of extracellular volume depletion caused by diuretic administration. In particular, this study was undertaken: a) to evaluate whether and to which extent, AA + D can reverse the functional GFR impairment induced by salt depletion, without volume restoration; b) to study whether any relationship may be found between the GFR in normal condition (the so-called "resting" GFR), and/or the renal functional reserve and the GFR impairment induced by salt depletion, in order to understand the role of both "resting" GFR and RFR in the degree of renal dysfunction induced by salt depletion. In control conditions the i.v. infusion of AA + D significantly increased RPF (+ 41% vs. baseline period) with a mean absolute increase of 211 ml/min. A similar pattern was observed in GFR behavior (+ 31.5% with 34 ml/min of mean absolute increase). A significant inverse exponential relationship was observed between GFR before AA + D i.v. infusion ("resting" GFR) and renal functional reserve (P < 0.05). suggesting that, in normal conditions, these inversely related parameters may widely vary according to the tone of the glomerular arterioles. Following salt depletion, we observed a variable degree of GFR impairment. Both GFR and RPF were significantly decreased (-25.9%, P < 0.05 and -29%. P < 0.05, respectively). The GFR impairment was mainly caused by a significant increase in tone of glomerular arterioles presumably induced by vasoactive substances (angiotensin, catecholamines) as mirrored by the increase of both plasma renin activity (PRA) and urinary norepinephrine (NE) excretion (+ 164% and +426%, respectively, vs. control period). AA + D infusion after salt depletion determined a striking rise of both GFR (+30 ml/min, corresponding to 37%) and RPF (+ 193 ml/min, corresponding to 31%) versus the baseline study of salt depleted condition. The GFR value obtained by AA + D i.v. infusion in the normal condition, however, was not reached presumably because of persistence of extracellular volume contraction, which was confirmed by the persistence of high values of PRA and NE urinary excretion and low values of urinary sodium excretion after AA + D i.v. infusion. GFR impairment due to salt depletion was directly related to the "resting" GFR (P < 0.05) and inversely related to the RFR (P < 0.01): the latter relationship suggests that the greater the "resting" tone of glomerular arterioles (and consequently the value of the RFR), the more minor the role of renal vasoconstriction in causing the fall of GFR following salt depletion. Finally, AA + D infusion in the salt depleted condition induced a GFR increase that is inversely related to the GFR value obtained after salt depletion (P < 0.05). This finding suggests that glomerular arteriolar tone influences, also in a salt depletion condition, the response to AA + D infusion: subjects with a lower GFR (with a greater vasoconstriction), in fact, show a greater increase in GFR after the infusion of these vasodilating substances.