A useful diagnostic agent: 4-Aminohippuric acid

Description

4-Aminohippuric acid is also known as Aminohippuric acid or para-aminohippuric acid (PAH). This substance is a natural compound belonging to the amino acid group. P-Aminohippurate is an organic acid that is filtered by the glomerulus and actively secreted by the proximal tubule. It is a newly developed ligand for mixed‐mode chromatography with a commercial resin named Nuvia cPrime.

Uses

4-Aminohippuric acid is used as a targeted therapeutic agent for the ACBD4 gene in hepatitis B virus-related hepatocellular carcinoma[1]. As a derivative of hippuric acid, it is a diagnostic agent useful in medical tests involving the kidney used in the measurement of renal plasma flow. During World War II, para-amino hippurate was given along with penicillin to prolong the time penicillin circulated in the blood. Because both penicillin and para-aminohippurate compete for the same transporter in the kidney, administering para-aminohippurate with penicillin decreased the clearance of penicillin from the body by the kidney, providing better antibacterial therapy.

Renal Plasma Flow

Inulin and p-amino hippuric acid (PAH) clearances are used for the estimation of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). The renal extraction ratio of PAH in a normal individual is approximately 0.92. This means that unlike inulin and creatinine, which are filtered in the glomerulus and ignored by the rest of the kidney, aminohippuric acid is both filtered and secreted, being almost entirely removed from the bloodstream in a normal kidney. The clearance of PAH is constant and high at low plasma [PAH], below the Tm PAH. Under these circumstances, the blood that perfuses the secreting portions of the nephron is nearly completely cleared of PAH. Under these conditions, the clearance of PAH approximates the effective renal plasma flow (ERPF). At high PPAH that exceeds the renal threshold, the clearance no longer approximates the ERPF[2].

RPF is calculated by the clearance of para-aminohippuric acid (PAH), as at low concentrations this compound is completely cleared from the plasma by renal tubular filtration and secretion in a single pass.

RPF=C_PAH=U_PAH×V/P_PAH

where RPF = renal plasma flow in mL/min, C_PAH = clearance of PAH in mL/min, U_PAH = urine concentration of PAH in mg/mL, V = urine flow rate in mL/min, and P_PAH = plasma concentration of PAH in mg/mL.

References

[1] Huang H, et al. Acyl-CoA Binding Domain Containing 4 Polymorphism rs4986172 and Expression Can Serve as Overall Survival Biomarkers for Hepatitis B Virus-Related Hepatocellular Carcinoma Patients After Hepatectomy. Pharmacogenomics and Personalized Medicine, 2022; 15: 277—300.

[2] Meltzer J. Renal Physiology. Pharmacology and Physiology for Anesthesia (Second Edition), 2019; 782-794