Amino acid loading disrupts whole kidney proximal glomerular-tubular balance in humans

The effect of amino acid infusion on proximal glomerular-tubular balance (PG-TB) was studied in twelve healthy two-kidney volunteers (2K) and eight uninephrectomized subjects (1K) in similar sodium and protein balance, to provide an extended range of values for renal function. Amino acid infusion induced a reversible significant increase in GFR: +23 +/- 4 and +18 +/- 3 ml/min/1.73 m2 in 2K and 1K respectively (p < 0.001), but not in absolute proximal reabsorption (APR, calculated as inulin clearance--lithium clearance): +8 +/- 3 and +6 +/- 3 ml/min/1.73 m2 respectively, NS. Consequently, the fractional increases in APR for both two kidney- and one kidney-subjects (+11 +/- 4 and +14 +/- 6%) were less than the fractional increases in GFR (+20 +/- 3 and 25 +/- 4%), and the effectiveness of PG-TB was significantly decreased to 53.2 and 55.9% (p < 0.001). Urinary sodium excretion also increased by 116 +/- 24 and 95 +/- 29 mumol/min/1.73 m2 in 2K (p < 0.001) and 1K (p < 0.01) respectively. Urinary excretion of guanosine 3',5'-cyclic monophosphate (cGMP) simultaneously increased (p < 0.001) by 223 +/- 77 and 350 +/- 135 pmol/min/1.73 m2 during infusion of amino acids in 1K and 2K respectively. In the whole group of subjects, impairment of the PG-TB was inversely related to the increase in urinary cGMP (p < 0.05). The results demonstrate that amino acid infusion disrupts proximal glomerular-tubular balance in humans due to non-proportional alterations in glomerular filtration rate and proximal reabsorption, and they suggest that a NO-dependent mechanism may be involved in the disruption.