Division of Pharmaceutical Sciences, School of Pharmacy, The University of Jordan, Amman, 11942, Jordan.
Department of Medical Laboratory Sciences, Jordan University of Science and Technology, Irbid, 22110, Jordan.
Sci Rep. 2023 Apr 15;13(1):6161. doi: 10.1038/s41598-023-33377-8.
Chronic kidney disease (CKD) is a serious public health problem characterized by progressive kidney function loss leading to end-stage renal disease (ESRD) that demands dialysis or kidney transplantation. Early detection can prevent or delay progression to ESRD. The study aimed to gain new insights into the perturbed biochemical reactions and to identify novel distinct biomarkers between ESRD and CKD. Serum samples of 32 patients with ESRD (n = 13) and CKD (n = 19) were analyzed using chemical isotope labeling liquid chromatography-mass spectrometry metabolomics approach. A total of 193 metabolites were significantly altered in ESRD compared to CKD and were mainly involved in aminoacyl-tRNA biosynthesis, branched-chain amino acid (BCAA) biosynthesis, taurine metabolism, and tryptophan metabolism. Three kynurenine derivatives, namely, 2-aminobenzoic acid, xanthurenic acid, and hydroxypicolinic acid were upregulated in ESRD compared to CKD due to the significant decrease in glomerular filtration rate with the progression of CKD to ESRD. N-Hydroxy-isoleucine, 2-aminobenzoic acid, and picolinic acid yielded AUC > 0.99 when analyzed using Receiver Operating Characteristic (ROC) analysis. Our findings suggest that inhibiting the kynurenine pathway might be a promising target to delay CKD progression and that metabolites with high discriminative ability might serve as potential prognostic biomarkers to monitor the progression of CKD to ESRD or used in combination with current markers to indicate the status of kidney damage better.
慢性肾脏病（CKD）是一种严重的公共卫生问题，其特征是肾功能逐渐丧失，导致终末期肾病（ESRD），需要透析或肾移植。早期发现可以预防或延缓 ESRD 的进展。本研究旨在深入了解失调的生化反应，并确定 ESRD 和 CKD 之间新的独特生物标志物。采用化学同位素标记液相色谱-质谱代谢组学方法分析了 32 例 ESRD（n=13）和 CKD（n=19）患者的血清样本。与 CKD 相比，ESRD 中有 193 种代谢物显著改变，主要涉及氨酰-tRNA 生物合成、支链氨基酸（BCAA）生物合成、牛磺酸代谢和色氨酸代谢。由于 CKD 进展为 ESRD 时肾小球滤过率显著下降，三种犬尿氨酸衍生物，即 2-氨基苯甲酸、黄嘌呤酸和羟基吡啶酸在 ESRD 中上调。与 CKD 相比，N-羟基异亮氨酸、2-氨基苯甲酸和吡啶酸的 AUC>0.99 ，当使用接收者操作特征（ROC）分析进行分析时。我们的研究结果表明，抑制犬尿氨酸途径可能是延缓 CKD 进展的有前途的靶点，而具有高区分能力的代谢物可能作为潜在的预后生物标志物，用于监测 CKD 向 ESRD 的进展，或与现有标志物联合使用，以更好地指示肾脏损伤的状况。
