We investigated the effects of hypotonic saline-induced modifications of extracellular volume and sodium handling on the renal and metabolic response to amino acids (AA). Renal hemodynamics (Inutest, p-aminohippurate clearance), plasma AA, and glucagon levels, as well as urea and sodium excretion, were studied in seven adult volunteers infused for 2 h, on six separate occasions, according to the following protocols: 1) high-AA solution (300 mg.min(-1).1.73 m(-2)); 2) low-AA. solution (150 mg.min(-1).1.73 m(-2)); 3) low AA + 2,000 ml/1.73 m(2) of 0.23% saline solution; 4) high AA + 0.23% saline; 5) high AA + 0.45% saline; and 6) 0.45% saline alone. The glomerular filtration rate (GFR) rise induced by the high-AA solution was similar to that induced by the low-AA, solution (Delta GFR = +24 +/- 6 and +20.2 +/- 7 ml.min(-1).1.73 m(-2), respectively), whereas the plasma AA and glucagon levels and urea excretion rate increases were related to AA dose. The addition of 0.23% saline to the low-AA solution and of 0.45% saline to the high-AA solution blunted the renal hemodynamic response (Delta GFR = +6.6 +/- 10.1 and +11.4 +/- 8.3 ml.min(-1).1.73 m(-2), respectively) without modifying the pattern of plasma AA and glucagon levels and urea excretion observed with the AA infusion alone. Urinary sodium excretion increased from baseline with each protocol and rose even further when saline was added to AA. A negative correlation (r = -0.38, P < 0.05) was found between the changes from basal values in GFR and those in sodium excretion rate with high-AA infusion at different levels of sodium concentration. These data suggest that AA-induced hyperfiltration might be blunted by hypotonic saline infusion, possibly through an acute modification of renal sodium handling and extracellular volume.

In order to investigate the renal effects of amino acids (AA) with different metabolic fate, we compared the changes in glomerular and tubular function, nitrogen metabolism and glucoregulatory hormones in 7 volunteers during two infusions, one of a complete solution of amino acids (MIX-AA), which included five AA electively metabolized at the splanchnic level, and the other of a solution containing only essential AA (EAA), which escape splanchnic metabolism. MIX-AA increased GFR and RPF (from 104 ± 6 to 122 ± 13 and from 488 ± 46 to 572 ± 34 ml/min/1.73 m2), stimulated splanchnic metabolism as demonstrated by rises in urinary urea excretion (from 20.7 ± 2 to 30.6 ± 7.5 mg/min/1.73 m2) and the plasma glucagon/insulin ratio (from 21.4 ± 13 to 26.7 ± 15), and caused increases in fractional excretion of AA, FeNa and free-water clearance. During MIX-AA infusion significant correlations were observed between the individual values of GFR and the urea excretion rate (r = 0.66), and between GFR modifications (ΔGFR) and the plasma glucagon/plasma insulin ratio (r = 0.40). No change in renal function, urea excretion and the glucagon/insulin ratio was observed with EAA. An intermediate splanchnic step (increased plasma glucagon/insulin ratio and ureagenesis) seems necessary in the pathway leading to the nonessential AA-induced rise in GFR; this might stimulate an ultimate intrarenal pathway (possibly involving the diluting segment) via a still undefined mechanism.