Analysis of non-targeted serum metabolomics in patients with chronic kidney disease and hyperuricemia

Abstract

ABSTRACT Hyperuricemia (HUA) is a common complication of chronic kidney disease (CKD). Conversely, HUA can promote the disease progression of CKD. However, the molecular mechanism of HUA in CKD development remains unclear. In the present study, we applied ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to analyze the serum metabolite profiling of 47 HUA patients, 41 non-hyperuricemic CKD (NUA-CKD) patients, and 51 CKD and HUA (HUA-CKD) patients, and then subjected to multivariate statistical analysis, metabolic pathway analysis and diagnostic performance evaluation. Metabolic profiling of serums showed that 40 differential metabolites (fold-change threshold (FC) > 1.5 or<2/3, variable importance in projection (VIP) > 1, and p < 0.05) were screened in HUA-CKD and HUA patients, and 24 differential metabolites (FC > 1.2 or<0.83, VIP>1, and p < 0.05) were screened in HUA-CKD and NUA-CKD patients. According to the analysis of metabolic pathways, significant changes existed in three metabolic pathways (compared with the HUA group) and two metabolic pathways (compared with the HUA-CKD group) in HUA-CKD patients. Glycerophospholipid metabolism was a significant pathway in HUA-CKD. Our findings show that the metabolic disorder in HUA-CKD patients was more serious than that in NUA-CKD or HUA patients. A theoretical basis is provided for HUA to accelerate CKD progress.