Characterization of tubular functional capacity in humans using para-aminohippurate and famotidine

Background. Renal drug excretion by glomerular filtration and active tubula r secretion may be altered by factors such as acute and chronic renal disea se, nephrotoxins, and drug interactions. Thus, accurate and reproducible me thods for quantitation of glomerular filtration rate (GFR) and tubular func tional capacity are critical. Methods. We utilized a four-step sequential infusion method to characterize anionic [para-aminohippurate (PAH)I and cationic (famotidine) tubular func tional capacity in healthy volunteers. Filtration and secretion rates were quantitated from renal clearance and iothalamate-derived GFR determinations . Results. Concentration-dependent renal clearance of PAH was observed at pla sma concentrations >100 mg/L; renal clearances were 442 +/- 131 (mean +/- S D), 423 +/- 94, 233 +/- 45, and 152 +/- 18 mL/min/1.73 m(2) at plasma conce ntrations of 18 +/- 2, 92 +/- 5, 291 +/- 47 and 789 +/- 28 mg/L, respective ly. The apparent affinity (K-m) and maximum secretory capacity (Tm-PAH) wer e 141 +/- 70 mg/L and 71 +/- 16 mg/min/1.73 m(2), respectively. The unbound renal clearance and tubular secretory clearance of famotidine were 384 +/- 70 and 329 +/- 78 mL/min/1.73 m(2), respectively, and were not significant ly correlated with the unbound plasma concentrations, which ranged from 126 to 2659 ng/mL. The rate of tubular secretion was linear at unbound plasma concentrations up to 2659 ng/mL. Conclusions. These data indicate that a sequential infusion method using PA H may be used to characterize the anionic secretory component of proximal t ubular function. The tubular clearance of famotidine may be a suitable inde x of the cationic secretory capacity of the proximal tubule in humans. Satu ration of the cationic secretory pathway was not observed, and further inve stigation into parallel pathways of cationic secretion, such as p-glycoprot ein, may be warranted.