In vivo indicator dilution kinetics of PAH transport in dog kidney.

Abstract

In vivo multiple indicator-dilution (MID) data were analyzed using a computer-assisted mathematical model of transepithelial cell transport to determine p-aminohippuric acid (PAH) transport kinetics across the proximal tubular antiluminal (ALM) and luminal (LM) membranes. A bolus of 125I-labeled albumin (plasma reference), [14C]creatinine (interstitial reference), and tracer [3H]PAH was injected into the left renal artery of anesthetized mongrel dogs (n = 21), and immediate serial sampling of the left renal venous and left and right urine outputs was performed (control). MID runs were then repeated in the same dog following intravenous infusion of unlabeled PAH. For all plasma PAH concentrations ([PAH]P), the steady-state unidirectional flux coefficients were calculated at the ALM and LM. The computer-derived unidirectional flux coefficients were in keeping with active ALM transport and passive, carrier-mediated LM transport. The Km calculated for ALM uptake (interstitium to cell) was 0.51 mM. PAH transport was completely inhibited by probenecid. As [PAH]P increased, the renal vein mean transit time ratio t[3H]PAH/t[14C]creatinine was greater than 1.0, indicating backflux from cells into the interstitium, then declined toward unity, as ALM and LM transport became saturated. This study, which used PAH as a model substrate demonstrated the feasibility of utilizing computer-assisted mathematical models to quantitate the kinetics of transepithelial transport from in vivo experimentation.