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

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 enzymelinked 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.

Metformin Can Decrease Serum levels of 12(S)-Hydroxyeicosatetraenoic Acid in Adults with Type 2 Diabetes Mellitus and Diabetic Kidney Disease

“…12(S)-HETE was also moderately correlated with ACR and uAER and had a great prediction of DKD. Our results are consistent with the previous study that revealed the association between serum 12(S)-HETE level and diabetic kidney disease [14]. The slight decrease of serum 12(S)-HETE in patients of G3a ~ G3b and A3 groups may suggest a greater prediction role of 12(S)-HETE at the early stage of DKD which needs further studies.…”

“…In ammation has long been considered as a pivotal factor in dyslipidemia, so our results might provide a clue for 12(S)-HETE promoting the dyslipidemia in the development of DKD through in ammatory pathways. In previous clinical studies, 12(S)-HETE was identi ed as an important biomarker to predict and diagnose the onset and progression of DKD and 12-HETE/PGI2 ratio was showed to be correlated with albuminuria in diabetes mellitus [7,14]. These clinical data and our results were consistent with preclinical ndings of 12(S)-HETE in DKD and provided a potential target of 12(S)-HETE in preventing the development of DKD, which can help us demonstrate the undergoing pathogenesis in T2DM patients who develop DKD even with intensive glycemic control.…”

“…12(S)-HETE has been demonstrated to work in association with angiotensin II and transforming growth factor-β (TGF-β) to induce brotic changes in diabetic kidneys [13]. Studies also showed that serum and urine levels of 12(S)-HETE signi cantly increased in patients with DKD and was associated with disease severity [7,14]. These results suggested the pivotal role of 12(S)-HETE in the pathogenesis of diabetic nephropathy [15].…”