Abstract: TH-PO477

Decreased Serum Sulfatide Level and Hepatic Sulfatide Synthesis Ability in 5/6 Nephrectomy CKD Model Mice

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 303 CKD: Epidemiology, Outcomes - Cardiovascular

Authors

  • Yamada, Yosuke, Shinshu University , Matsumoto, Nagano, Japan
  • Yamaka, Kosuke, Shinshu University , Matsumoto, Nagano, Japan
  • Inui, Keita, Shinshu University , Matsumoto, Nagano, Japan
  • Kamijo, Yuji, Shinshu University School of Medicine, Matsumoto, Japan
Background

Chronic kidney disease (CKD) is increasing worldwide. As CKD is an independent risk factor of critical cardiovascular disease, its pathological clarification has become imperative.
We earlier reported that the serum level of sulfatide, a glycosphingolipid, was decreased in CKD patients and that the risk of cardiovascular disease was higher in end-stage renal disease patients with diminished serum sulfatide. Accordingly, we have hypothesized that CKD impairs the ability to synthesize sulfatide and lowers serum sulfatide concentration to adversely affect peripheral circulation and contribute to cardiovascular disease onset. However, patients with CKD often possess comorbidities, such as hypertension and diabetes, which may act as confounders. It is therefore challenging to determine whether or not CKD influences sulfatide synthesis and serum level.
To address this issue, CKD model mice whose renal function was impaired by 5/6 nephrectomy were produced for evaluation of serum sulfatide level and sulfatide synthesis ability in the liver, which is the major origin of sulfatide in the serum.

Methods

Of 14 C57B6J mice, 6 underwent 5/6 nephrectomy in which two thirds of the right kidney was removed at 11 weeks of age and the whole left kidney was removed at 12 weeks of age. The remaining 8 mice were used as controls and underwent sham operations of skin incisions only at 11 and 12 weeks of age, respectively. Both groups were maintained under identical circumstances post-operatively. The animals were sacrificed 12 weeks after the final operation and sulfatide concentrations in the serum and liver tissue were measured by Matrix-assisted laser desorption/ionization-time of flight mass spectrometry.

Results

The 5/6 nephrectomy mice developed CKD with elevated serum creatinine, urea nitrogen, and urine volume as compared with control mice. There were no significant differences in blood pressure or pulse rate between the groups. Serum sulfatide level and liver sulfatide concentration were significantly decreased in test mice versus controls (both P<0.01).

Conclusion

CKD is a cause of decreased serum sulfatide and diminished sulfatide-synthesizing ability in the liver. Further research is needed to investigate whether serum sulfatide level abnormalities contribute to the development of cardiovascular disease.