Abstract

Background and Objectives. Diabetic kidney disease is a leading cause of chronic kidney disease and end-stage renal disease across the world. Early identification of DKD is vitally important for the effective prevention and control of it. However, the available indicators are doubtful in the early diagnosis of DKD. This study is aimed at determining novel sensitive and specific biomarkers to distinguish DKD from their counterparts effectively based on the widely targeted metabolomics approach. Materials and Method. This case-control study involved 44 T2DM patients. Among them, 24 participants with DKD were defined as the cases and another 20 without DKD were defined as the controls. The ultraperformance liquid chromatography-electrospray ionization-tandem mass spectrometry system was applied for the assessment of the serum metabolic profiles. Comprehensive analysis of metabolomics characteristics was conducted to detect the candidate metabolic biomarkers and assess their capability and feasibility. Result A total of 11 differential metabolites, including Hexadecanoic Acid (C16:0), Linolelaidic Acid (C18:2N6T), Linoleic Acid (C18:2N6C), Trans-4-Hydroxy-L-Proline, 6-Aminocaproic Acid, L-Dihydroorotic Acid, 6-Methylmercaptopurine, Piperidine, Azoxystrobin Acid, Lysopc 20:4, and Cuminaldehyde, were determined as the potential biomarkers for the DKD early identification, based on the multivariable generalized linear regression model and receiver operating characteristic analysis. Conclusion Serum metabolites might act as sensitive and specific biomarkers for DKD early detection. Further longitudinal studies are needed to confirm our findings.

Highlights

  • Type 2 diabetes mellitus (T2DM) affects over 366 million people worldwide (6.4% of the adult population) and this number is expected to rise to 552 million by 2030 [1]

  • The diagnostic criteria for CKD were renal structural impairment and dysfunction caused by a variety of factors for at least 3 months, including normal and abnormal glomerular filtration rate (GFR), pathological damage, blood or urine components, abnormalities, and imaging abnormalities, or an unexplained GFR < 60 mL/min/1:73 m2 that persisted for 3 months

  • In addition to fat-free fatty acid metabolites, this study revealed that organic acids and their derivatives are related to diabetic kidney disease (DKD). 6-Aminocaproic Acid and L-Dihydroorotic Acid are organic acids; they bear association with DKD (VIP > 3, p ≤ 0:001, AUC > 0:70)

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Summary

Introduction

Type 2 diabetes mellitus (T2DM) affects over 366 million people worldwide (6.4% of the adult population) and this number is expected to rise to 552 million by 2030 [1]. DKD is a major cause of chronic kidney disease and end-stage renal disease (ESRD) across the world, accompanied by an increased risk of mortality and cardiovascular disease. With economic growth and lifestyle changes, there are more and more T2DM patients at risk of progressive renal function loss. A large number of studies confirmed that hyperglycemia is the most important risk factor for DKD. This study is aimed at determining novel sensitive and specific biomarkers to distinguish DKD from their counterparts effectively based on the widely targeted metabolomics approach. This case-control study involved 44 T2DM patients. A total of 11 differential metabolites, including Hexadecanoic Acid (C16:0), Linolelaidic Acid (C18:2N6T), Linoleic Acid (C18:2N6C), Trans-4-Hydroxy-L-Proline, 6-Aminocaproic Acid, L-Dihydroorotic Acid, 6Methylmercaptopurine, Piperidine, Azoxystrobin Acid, Lysopc 20:4, and Cuminaldehyde, were determined as the potential biomarkers for the DKD early identification, based on the multivariable generalized linear regression model and receiver operating characteristic analysis.

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