Characterization of Tubular Functional Capacity in Humans Using Para-aminohippurate and Famotidine
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AbstractCharacterization of tubular functional capacity in humans using para-aminohippurate and famotidine. Background Renal drug excretion by glomerular filtration and active tubular secretion may be altered by factors such as acute and chronic renal disease, nephrotoxins, and drug interactions. Thus, accurate and reproducible methods for quantitation of glomerular filtration rate (GFR) and tubular functional capacity are critical. Methods We utilized a four-step sequential infusion method to characterize anionic [para-aminohippurate (PAH)] and cationic (famotidine) tubular functional 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 plasma concentrations> 100 mg/L; renal clearances were 442 131 (mean SD), 423 94, 233 45, and 152 18 mL/min/1.73 m2 at plasma concentrations of 18 2, 92 5, 291 47 and 789 28 mg/L, respectively. The apparent affinity (Km) and maximum secretory capacity (TmPAH) were 141 70 mg/L and 71 16 mg/min/1.73 m2, respectively. The unbound renal clearance and tubular secretory clearance of famotidine were 384 70 and 329 78 mL/min/1.73 m2, respectively, and were not significantly 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 PAH may be used to characterize the anionic secretory component of proximal tubular function. The tubular clearance of famotidine may be a suitable index of the cationic secretory capacity of the proximal tubule in humans. Saturation of the cationic secretory pathway was not observed, and further investigation into parallel pathways of cationic secretion, such as p-glycoprotein, may be warranted.
CitationDowling, T. C., Frye, R. F., Fraley, D. S., & Matzke, G. R. (2001). Characterization of tubular functional capacity in humans using para-aminohippurate and famotidine. Kidney International, 59(1), 295–303.
Keywordrenal tubular secretion
ATP-Binding Cassette, Sub-Family B, Member 1