Para-aminohippurate

Explain how plasma clearance of para-aminohippuric acid is used to determine the effective renal plasma flow... 

A substance that fulfills these criteria is para-aminohippuric acid (PAH). All of the PAH not filtered at the glomerulus is secreted by the proximal tubule. The net effect is that all of the plasma flowing through the nephrons is completely cleared of PAH. It is important to note that about 10 to 15% of the total renal plasma flow supplies regions of the kidneys that are not involved with filtration or secretion. Consequently, this plasma cannot be cleared of PAH. Therefore, the plasma clearance of PAH provides a measurement of the effective renal plasma flow, that is, the volume of plasma that actually flows through the nephrons. The ERPF is normally about 625 ml/ min. (This value is based on a renal blood flow of about 1.1 1/min and a hematocrit of about 42.)... 

Leier I, Hummel-Eisenbeiss J, Cui Y, Keppler D. ATP-dependent para-aminohippurate transport by apical multidrug resistance protein MRP2. Kidney Int 2000 57 1636-1642. 

Leier I, Hummel-Eisenbeiss J, Cui Y, Keppler D (2000) ATP-dependent para-aminohippurate transport by apical multidrug resistance protein MRP2. Kidney Int 57 1636-1642 Leier I, Jedlitschky G, Buchholz U et al. (1994a) The MRP gene encodes an ATP-dependent export pump for leukotriene C4 and structurally related conjugates. J Biol Chem 269 27807-27810... 

Another model substance that is used experimentally for the assessment of kidney function is para-aminohippuric acid (p-AH). p-AH appears in the urine not just by filtration but mainly by active secretion in the proximal tubule. This active transport process occurs in two steps (Figure 2.19a) In the first step, p-AH is exchanged at the basolateral membrane of the proximal tubule cell against a-ketoglutarate or other divalent anions. This exchange is driven by the membrane potential (the interior of the tubule cell is electrically negative relative to the outside, as is the case with essentially all cells). 

Platelet-activating factor Para-aminohippuric acid Percutaneous acetic acid injection Punction/Aspiration/Injection/Re-Aspiration Perinuclear antineutrophihc cytoplasmic antibody... 

K. J. Ullrich, G. Rumrich, T. Wieland, and W. Dekant, Contraluminal para-aminohippurate (PAH) transport in the proximal tubule of the rat kidney VI Specificity Amino acids, their N-methyl-, N-acetyl-, and W-benzoylderiva-tives glutathione- and cysteine conjugates, di- and oligopeptides, Pflugers Arch., 415 342-350 (1989). 

Diatrizoate can interfere with para-aminohippuric acid extraction studies (SEDA-15, 502) (321). 

Ullrich KJ, Rumrich G. Luminal transport step of para-aminohippurate (PAH)-transport from pah-loaded proximal tubular cells into the tubular lumen of the rat kidney n vivo. Pfiugers Arch 1997 433(6) 735-743... 

In patients with normal renal function, 70 to 90% of an intravenous dose of vancomycin is excreted in the urine unchanged by glomerular filtration. The serum elimination half-life in patients with normal renal function is variable, but averages 6 hours [171]. However, terminal half-lives ranging from 3 to 11 hours have been observed [184]. In anuric patients, the serum half-life increases markedly to 6 to 10 days [171]. The liver may also be involved in the disposition of vancomycin as dose adjustments have been required in patients with severe liver dysfunction [172]. An interesting study by Golper et al that compared systemic vancomycin clearance simultaneously with the renal clearances of vancomycin, creatinine, inulin and para-aminohippurate demonstrated a substantial non-renal clearance of vancomycin of 30%. In addition, the researchers found that the non-renal clearance of vancomycin was concentration dependent with a 10% greater clearance at serum concentrations of 14 mg/ ml as compared to 7 mg/ ml [185]. 

Para-aminohippurate (PAH)—A small molecule which is completely secreted from the tubules into urine, so that blood leaving the kidney is virtually free of PAH a marker that is often used to measure renal plasma flow (RPF). 

After incubation of renal cortical shces with mezlocillin there was no change in the accumulation of the organic anion para-aminohippurate (PAH) in shces when compared to control whereas a significant decrease in the accumulation of the cation tetraethylam-monium (TEA) occurred [10], suggesting a preferential sensitivity of organic cation transporter. 

Cassin S, Vogh B. Effect of hydrochlorothiazide on renal blood flow and clearance of para-aminohippurate and creatinine. Proc Soc Exp Biol Med 1966 122 970-973. 

Exhibiting a pattern of eicosanoid excretion noted in essential hypertension, lead-exposed workers showed an increase in TxB2 and a decrease in PGE2 and 6-keto-PGF] in fhe mine [63]. In contrast to the reabsorpfive defect of acute lead nephropathy, saturnine gout is characterized by renal retention of uric acid. The clearance and maximal secretion rate for para-aminohippurate have been found to be variable in patients with occupational lead nephropathy. A reduced maximal reabsorpfive rate for glucose has been reported, but simultaneous, matched controls were not obtained [69]. 

Renal accumulation is unaffected by probenecid and para-aminohippuric acid (PAH) (Lee and Blaufox 1985). Uptake is decreased by ACE inhibitors in the presence of renal artery stenosis (Hovinga et al. 1989 Kopecky et al. 1990). 

In vivo experiments were performed using para-aminohippuric acid (PAH) as a marker inside the polymers. Data of rats PAH concentration in the urine after implantation showed that the PAH concentration in the urine was pronounced during the exposure and mainly in the timespan just after the exposure. The delay was presumably the diffusion time from the implantation site to the bloodstream and then the removal by the kidneys. When control animals were treated by the same procedure, i.e., placing the ultrasonic applicator head over the treated area with the power level of the ultrasound set to zero, no effect of the ultrasound could be detected... 

In terms of drug disposition, OATl is the most important member of this transport family. Expressed mainly in the kidney tubule cell, OATl is a dicarboxylate exchange protein that is responsible for basolateral uptake of organic anions such as para-aminohippurate (PAH). OATl mediates the excretion of a diverse array of substrates, including environmental toxins. Substrates for this transporter include antibiotics, antiviral nucleoside analogs, and nonsteroidal anti-inflammatory medications. In fact, more than 100 medications and toxic compounds have been found to interact with OATl. 

Plasma clearance of para-aminohippuric acid (PAH) is almost equal to a plasma flow. 

Schali, Ch., F. Roch-Ramel Transport of urate and para-aminohippurate in isolated, nonperfused proximal renal tubules of the pig kidney. Kidney Int. 17 860-861 (1980b) (abstr.). 

An indirect measurement of RBF can be made using para-aminohippuric acid (PAH) clearance. This molecule is an ideal marker of the effective renal plasma flow (eRPF), as it freely filters through the glomerulus, and any amotmt remaining in the peritubular capillary plasma is secreted into the proximal tubule. Therefore, essentially aU PAH passing through the kidneys appears in the urine. For this reason, the PAH clearance is directly proportional to the rate of plasma flow through the kidneys. If the hematocrit is known, the total renal blood flow can be easily calculated from the eRPF value. 

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