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Abstract: SA-PO521

Urinary L Type Fatty Acid Binding Protein Reflects the Degree of Renal Hypoxia in Spontaneously Diabetic Torii Fatty Rats

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Tanabe, Jun, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
  • Ichikawa, Daisuke, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
  • Kimura, Kenjiro, Tokyo Takanawa Hospital, Tokyo, Japan
  • Shibagaki, Yugo, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
  • Ikemori, Atsuko, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
Background

Tubulointerstitial damage is known to be strongly associated with renal prognosis in diabetic kidney disease (DKD). Because renal hypoxia is an aggravated factor for the tubulointerstitial damage, urinary marker which is capable of detecting the renal hypoxia, is useful for monitoring the DKD. The aim of this study is to reveal the correlation between urinary liver-type fatty acid binding protein (L-FABP) and renal hypoxia using novel model of type 2 diabetes with obesity.

Methods

Male spontaneously diabetic torii (SDT) fatty rats (n =6) were used as an animal model of type 2 diabetes with obesity. Age- and sex-matched Sprague–Dawley rats (SD) (n = 8) were used as controls. Body weight, systolic blood pressure and blood glucose levels were measured at 8, 12, 16 and 24 weeks of age. Urine samples, serum and kidney tissues were obtained at 24 weeks of age. Microvascular blood flow index (BFI) in renal cortex was measured using diffuse correlation spectroscopy (DCS) before removing the kidney at 24weeks of age.

Results

Obesity, hyperglycemia and hypertension were observed in the SDT fatty rats. Mild glomerular hypertrophy and sclerosis, moderate interstitial inflammation and fibrosis, and accumulation of renal oxidative protein were significantly observed in the SDT fatty rats compared to the SD rats. While frequency of peritubular endothelial cells and phospho- endothelial nitric oxide synthase levels were similar between the SDT fatty rats and the SD rats, the degrees of renal hypoxia-inducible factor-1a expression significantly increased and renal vascular endothelial growth factor expression levels did not increase in the SDT fatty rats compared to the SD rats. Urinary L-FABP levels in the SDT fatty rats were significantly higher and renal microvascular BFIs in the SDT fatty rats were significantly lower compared to the SD rats. The levels of urinary L-FABP were significantly positively correlated with renal HIF-1a expression levels and were negatively correlated with renal microvascular BFIs.

Conclusion

Urinary L-FABP levels reflected the degree of renal hypoxia in DKD of type 2 diabetic animal model. In clinical practice, urinary L-FABP may be useful for monitoring DKD in type 2 diabetic patients as a renal hypoxic marker.