Journal
JOURNAL OF DIABETES INVESTIGATION
Volume 11, Issue 2, Pages 441-449Publisher
WILEY
DOI: 10.1111/jdi.13154
Keywords
Ceramide; Tandem mass spectrometry; Urine
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Funding
- Leading Advanced Projects for Medical Innovation (LEAP) from Japan Agency for Medical Research and Development
- JSPS KAKENHI [16H06236]
- Charitable Trust Laboratory Medicine Research Foundation of Japan
- [15H05906]
- Grants-in-Aid for Scientific Research [16H06236] Funding Source: KAKEN
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Aims/Introduction Sphingolipids, such as ceramides and sphingosine, are involved in the pathogenesis of diabetes; however, the modulation of urinary sphingolipids in diabetic nephropathy has not been fully elucidated. Therefore, we aimed to develop a simultaneous measurement system for urinary sphingolipids using liquid chromatography-tandem mass spectrometry and to elucidate the modulation of urinary sphingolipids in diabetic nephropathy. Materials and Methods We established a simultaneous measurement system for the urinary sphingosine, dihydrosphingosine, and six ceramide species (Cer d18:1/16:0, Cer d18:1/18:0, Cer d18:1/18:1, Cer d18:1/20:0, Cer d18:1/22:0 and Cer d18:1/24:0), and we examined the urinary sphingolipids in 64 type 2 diabetes patients and 15 control participants. Results The established measurement system for the urinary sphingolipids showed good precision for Cer d18:1/16:0, Cer d18:1/20:0, Cer d18:1/22:0 and Cer d18:1/24:0. We observed that the urinary levels of Cer d18:1/16:0, Cer d18:1/18:0, Cer d18:1/20:0, Cer d18:1/22:0 and Cer d18:1/24:0 were elevated in patients with stage 3 of diabetic nephropathy, and were correlated with urinary biomarkers, such as albumin and N-acetyl-beta-d-glucosaminidase, and sediment score. Conclusions Our method is useful for the measurement of ceramide in urine specimens, and urinary ceramides might be associated with the pathological condition of diabetic nephropathy, such as renal tubular injury.
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