To study the defective transport mechanism of
cystinuria, renal tubular reabsorption of
lysine or
arginine in normal and
cystinuria subjects was investigated by increasing the filtered load employing intravenous
amino acid infusion. In the normal group the
amino acid reabsorption rose with increases of the filtered load and reached a maximum (Tm). In the
cystinuria group the elevation of
amino acid reabsorption was poor at low filtered loads and some of the reabsorption rates fell below zero, whereas the tubular transport proceeded at a normal rate with a great increase of the filtered load. This might be explained as follows: At low filtered loads the filtered
amino acid in the tubular lumen in patients with
cystinuria is not absorbed into the cell because of a transport defect of the
luminal membrane of the tubular cell, causing a large amount of urinary
amino acid excretion. At high filtered loads the accumulated intraluminal
amino acid permeates the tubular cell by a passive diffusion and is transported to the capillary across the intact basolateral membrane, which in turn only brings about a small urinary loss of
amino acid. The infusion of
lysine or
arginine depressed the percentage of tubular reabsorption of other
dibasic amino acids in both groups. In the
cystinuria group the percentage of the dibasic
amino acid reabsorption dropped sharply with an initial load of the inhibitor, but no more depression of the percentage of reabsorption occurred with further loads of the inhibitor.