Albumin-bound kynurenic acid is an appropriate endogenous biomarker for assessment of the renal tubular OATs-MRP4 channel
作者机构：The First School of Clinical MedicineLanzhou UniversityLanzhou730000China School of PharmacyLanzhou UniversityLanzhou730000China
出 版 物：《Journal of Pharmaceutical Analysis》 (药物分析学报（英文版）)
年 卷 期：2023年第13卷第10期
页 面：1205-1220页
核心收录：
学科分类：1002[医学-临床医学] 100203[医学-老年医学] 10[医学]
基 金：supported by the National Natural Science Foundation of China(Grant Nos.:81803611,82160705,and U21A20424) the Natural Science Foundation of Gansu Province,China(Grant No.:21ZD4FA014)
主 题：Transporter Biomarker Kynurenic acid Renal tubular excretion
摘 要：Renal tubular secretion mediated by organic anion transporters(OATs)and the multidrug resistanceassociated protein 4(MRP4)is an important means of drug and toxin ***,there are no biomarkers to evaluate their *** aim of this study was to identify and characterize an endogenous biomarker of the renal tubular OATs-MRP4 ***-six uremic toxins were selected as candidate compounds,of which kynurenic acid was identified as a potential biomarker by assessing the protein-binding ratio and the uptake in OAT1-,OAT3-,and MRP4-overexpressing cell ***1/3 and MRP4 mediated the transcellular vectorial transport of kynurenic acid in *** kynurenic acid concentration was dramatically increased in rats treated with a rat OAT1/3(rOAT1/3)inhibitor and in rOAT1/3 double knockout(rOAT1/3^(-/-))rats,and the renal concentrations were markedly elevated by the rat MRP4(rMRP4)*** acid was not filtered at the glomerulus(99%of albumin binding),and was specifically secreted in renal tubules through the OAT1/3-MRP4 channel with an appropriate affinity(Km)(496.7 mM and 382.2 mM for OAT1 and OAT3,respectively)and renal clearance half-life(t1/2)in vivo(3.7±0.7 h).There is a strong correlation in area under the plasma drug concentration-time curve(AUC0et)between cefmetazole and kynurenic acid,but not with creatinine,after inhibition of *** addition,the phase of increased kynurenic acid level is earlier than that of creatinine in acute kidney injury *** results suggest that albumin-bound kynurenic acid is an appropriate endogenous biomarker for adjusting the dosage of drugs secreted by this channel or predicting kidney injury.
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