Metabolomics window into the role of acute kidney injury after coronary artery bypass grafting in diabetic nephropathy progression

Jiayi Wang; Wenzhe Yan; Xiang Zhou; Yu Liu; Chengyuan Tang; Youming Peng; Hong Liu; Lin Sun; Li Xiao; Liyu He

doi:10.7717/peerj.9111

Metabolomics window into the role of acute kidney injury after coronary artery bypass grafting in diabetic nephropathy progression

PeerJ. 2020 May 14:8:e9111. doi: 10.7717/peerj.9111. eCollection 2020.

Authors

Jiayi Wang¹, Wenzhe Yan², Xiang Zhou¹, Yu Liu¹, Chengyuan Tang¹, Youming Peng¹, Hong Liu¹, Lin Sun¹, Li Xiao¹, Liyu He¹

Affiliations

¹ Department of Nephrology, The Second Xiangya Hospital, Central South University, Key Lab of Kidney Disease and Blood Purification in Hunan, Changsha, China.
² Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, China.

Abstract

Introduction: Metabolomics has emerged as a valuable tool to discover novel biomarkers and study the pathophysiology of diabetic nephropathy (DN). However, the effect of postoperative acute kidney injury (AKI) on diabetes mellitus (DM) to chronic DN progression has not been evaluated from the perspective of metabolomics.

Methods: A group of type 2 diabetes mellitus (T2DM) inpatients, who underwent off-pump coronary artery bypass grafting (CABG), were enrolled in our study. According to whether postoperative AKI occurred, patients were grouped in either the AKI group (AKI, n = 44) or the non-AKI group (NAKI, n = 44). Urine samples were collected from these patients before and 24 h after operation. Six patients from the AKI group and six patients from the NAKI group were chosen as the pilot cohort for untargeted metabolomics analysis, with the goal of identifying postoperative AKI-related metabolites. To understand the possible role of these metabolites in the chronic development of renal injury among T2DM patients, trans-4-hydroxy-L-proline and azelaic acid were quantified by targeted metabolomics analysis among 38 NAKI patients, 38 AKI patients, 46 early DN patients (DN-micro group), and 34 overt DN patients (DN-macro group).

Results: Untargeted metabolomics screened 61 statistically distinguishable metabolites in postoperative urine samples, compared with preoperative urine samples. Via Venn diagram analysis, nine of 61 were postoperative AKI-related metabolites, including trans-4-hydroxy-L-proline, uridine triphosphate, p-aminobenzoate, caffeic acid, adrenochrome, δ-valerolactam, L-norleucine, 5'-deoxy-5'-(methylthio) adenosine, and azelaic acid. By targeted metabolomics analysis, the level of trans-4-hydroxy-L-proline increased gradually from the NAKI group to the AKI, DN-micro, and DN-macro groups. For azelaic acid, the highest level was found in the NAKI and DN-micro groups, followed by the DN-macro group. The AKI group exhibited the lowest level of azelaic acid.

Conclusions: The detection of urinary trans-4-hydroxy-L-proline after AKI could be treated as an early warning of chronic DN progression and might be linked to renal fibrosis. Urinary azelaic acid can be used to monitor renal function noninvasively in DM and DN patients. Our results identified markers of AKI on DM and the chronic progression of DN. In addition, the progression of DN was associated with AKI-like episodes occurring in DM.

Keywords: Acute kidney injury; Azelaic acid; Coronary artery bypass grafting procedure; Diabetic nephropathy; Metabolomics; Trans-4-hydroxy-l-proline.

Grants and funding

This work was supported by the National Natural Science Foundation of China (81870500, 81770714 and 81570622). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.