The renal transport of hippurate and protein‐bound solutes

Abstract

Measurement of the concentration of hippurate in the inferior vena cava and renal blood samples performed in 13 subjects with normal or near‐normal serum creatinine concentrations confirmed the prediction that endogenous hippurate was cleared on a single pass through the kidney with the same avidity as that reported for infused para‐amino hippurate. This suggests that a timed urine collection without infusion would provide a measure of effective renal plasma flow. Comparison of the arteriovenous concentration differences for a panel of protein‐bound solutes identified solutes that were secreted by the renal tubule and solutes that were subjected to tubular reabsorption.

Metabolic Features of Increased Gut Permeability, Inflammation, and Altered Energy Metabolism Distinguish Agricultural Workers at Risk for Mesoamerican Nephropathy

“…Increased urinary hippurate could reflect other processes as well. Increased urinary hippurate is associated with increased renal blood flow [ 37 ]. Urinary hippurate is also affected by consumption of hippurate and its precursors.…”

Enzymological Characterization of 64Cu-Labeled Neprilysin Substrates and Their Application for Modulating the Renal Clearance of Targeted Radiopharmaceuticals

“…In this context, [ 64 Cu]­Cu-NODAGA-NES2-TATE and [ 64 Cu]­Cu-NODAGA-NES3-TATE , which show the lowest kidney uptake, are metabolized to the cleavage fragments [ 64 Cu]­Cu-NODAGA-PAMBA-Nle-OH and [ 64 Cu]­Cu-NODAGA-PAMBA-G-OH , respectively. These radiometabolites resemble the structure of hippuric acid ( N -benzoylglycine), which undergoes a fast renal elimination due to glomerular filtration and tubular secretion . Furthermore, as mentioned in the introduction, 3′-[ 131 I]­iodohippuric acid was identified as fast eliminating species from a 3′-[ 131 I]­iodohippuryl N ε -maleoyl-lysine ([ 131 I]­HML)-labeled Fab .…”

“…For [ 64 These radiometabolites resemble the structure of hippuric acid (N-benzoylglycine), which undergoes a fast renal elimination due to glomerular filtration and tubular secretion. 77 Furthermore, as mentioned in the introduction, 3′-[ 131 I]iodohippuric acid was identified as fast eliminating species from a 3′-[ 131 I]iodohippuryl N ε -maleoyl-lysine ([ 131 I]HML)-labeled Fab. 27 In contrast, the cleavage fragments of [ 64 Characterization of the Triple-Targeting Radioligand [ 64 Cu]Cu-NODAGA-NES5-TATE.…”

Predicting complex kidney drug handling using a physiologically‐based pharmacokinetic model informed by biomarker‐estimated secretory clearance and blood flow

“…To estimate the OAT1/3‐mediated intrinsic secretion capacity, we used the iohexol‐GFR (iGFR) and kidney clearance of isovalerylglycine from each individual as model input values for GFR and KBF, respectively. We set the plasma unbound fraction of KA at 7% for all subjects, derived as the average from previous measurements in the literature of protein binding using different methodologies and also based on our finding that KA binding does not vary among patients with normal and impaired kidney function 17,22–24 …”

“…and also based on our finding that KA binding does not vary among patients with normal and impaired kidney function. 17,[22][23][24] After inputting GFR and KBF to the model, we simulated KA clearance using the mechanistic model allowing for a range (10-1000 L/h) of secretory clearance values applied to both basolateral uptake and apical efflux clearance.…”