12(S)-hydroxyeicosatetraenoic acid is significantly increased in diabetic kidney disease and associated with renal function decline

Diabetes Metab Res Rev. 2022 Sep;38(6):e3554. doi: 10.1002/dmrr.3554. Epub 2022 Jun 17.

Abstract

Aims: 12(S)-hydroxyeicosatetraenoic (12(S)-HETE), an alternate arachidonic acid metabolite, has been recently examined in metabolic disease. However, the role of 12(S)-HETE in diabetic kidney disease (DKD) remains unclear. We studied for the first time the relationship of serum 12(S)-HETE and DKD and renal function parameters in a Chinese population.

Materials and methods: We recruited 275 subjects who were diagnosed with type 2 diabetes (T2DM) for more than 10 years, including 149 DKD patients and 126 T2DM patients without DKD. Serum 12(S)-HETE was measured using the enzyme-linked immunosorbent assay.

Results: Serum 12(S)-HETE was significantly higher in DKD patients than controls [384.69 (77.54, 1003.05) pg/ml and 17.77 (8.11, 75.13) pg/ml, respectively, p < 0.0001]. Compared to controls, 12(S)-HETE was significantly increased in both macroalbuminuria and microalbuminuria groups (p < 0.0001). Further, the macroalbuminuria group also had a higher serum 12(S)-HETE level compared to the microalbuminuria group (p = 0.0063). Moreover, serum 12(S)-HETE was positively correlated with the albuminuria level (r = 0.5833, p < 0.0001), serum creatinine (r = 0.2725, p < 0.0001), and was negatively associated with the estimated glomerular filtration rate (r = -0.2085, p = 0.0005). Further, receiver operating characteristic analysis (ROC) revealed that 12(S)-HETE had a good performance of distinguishing DKD from controls (AUC 0.828) with a sensitivity of 0.913 and a specificity of 0.711.

Conclusion: Our findings revealed that serum 12(S)-HETE significantly associated with DKD and disease severity, suggesting that serum 12(S)-HETE may be used as a potential biomarker for the early diagnosis of DKD.

Keywords: 12(S)-hydroxyeicosatetraenoic acid; arachidonic acid metabolite; diabetic kidney disease; serum biomarker; type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albuminuria
  • Diabetes Mellitus, Type 2*
  • Diabetic Nephropathies* / diagnosis
  • Diabetic Nephropathies* / etiology
  • Humans
  • Hydroxyeicosatetraenoic Acids
  • Kidney / physiology

Substances

  • Hydroxyeicosatetraenoic Acids