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Abstract: PO0905

Lysophospholipids Predict Fast Decliners with Diabetic Kidney Disease

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic


  • Yoshioka, Kentaro, University of Tokyo School of Medicine, Bunkyo-ku, Tokyo, Japan
  • Hirakawa, Yosuke, University of Tokyo School of Medicine, Bunkyo-ku, Tokyo, Japan
  • Kojima, Kensuke, Kyowa Kirin Kabushiki Kaisha Kenkyu Kaihatsu, Chiyoda-ku, Tokyo, Japan
  • Nangaku, Masaomi, University of Tokyo School of Medicine, Bunkyo-ku, Tokyo, Japan
  • Inagi, Reiko, University of Tokyo Graduate School of Medicine School of Medicine, Bunkyo-ku, Tokyo, Japan

In type 2 diabetes, lipid metabolism disorder is frequently complicated due to insufficient insulin secretion and cytokines by visceral fat and regarded as one of the most important risk factors for renal dysfunction. However, specific lipid metabolites that have critical effects on renal dysfunction are not fully understood.


We performed the metabolomic analysis for patients with diabetic kidney disease (DKD) to identify novel metabolites related to renal prognosis. Plasma and urine biosamples in stage G3 DKD patients (n=135) are collected, and the whole metabolites of them were quantified by capillary electrophoresis mass spectrometry (CE-MS). Significantly fluctuating metabolites in patients with rapidly impaired renal function within 3 years (called “fast decliners”; about 10% in total) were statistically extracted. We also validated the metabolomic candidates with animal DKD model of SDT-fatty rats, or in vitro study using renal proximal tubular cells (HK-2).


In the clinical metabolomic analysis of the biosamples, over 250 metabolites, including lipids, glycates, and amino acids were identified by CE-MS. Among them, specific urinary lysophospholipids (named as LPLsX) in the fast decliners of DKD were significantly increased. The LPLsX were moderately correlated with eGFR decline after 3 years (r=0.42, p<0.01). In animal experiments, the level of LPLsX was also increased in both the urine and the kidney in the subnephrectomized SDT-fatty rats, while we did not see these damages in normal SD rats. In vitro experiments: the exposure of LPLsX to HK-2 induced apoptosis within 24 h and upregulated pro-apoptotic gene expressions. More physiological changes were investigated in refence to transcriptomic analysis, and we could find that LPLsX also deranged the lipid metabolism, estimated by intracellular lipid droplet accumulation, and increased the level of mitochondrial reactive oxygen species.


LPLsX predict “fast decliners” in DKD patients or DKD rats and may have crucial roles in renal tubular damage and dyslipidemia. Our findings provide new insights into the pathophysiological understanding of the relationship between lipid metabolism disorder and DKD progression.


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