ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: SA-PO1091

Urinary L-Type Fatty Acid-Binding Protein Is Useful for Evaluation of the Renoprotective Effect of Bardoxolone Methyl, a Nuclear Factor Erythroid 2-Related Factor 2 Activator

Session Information

Category: Hypertension

  • 1102 Hypertension: Basic and Experimental - Renal Causes and Consequences

Authors

  • Hisamichi, Mikako, Division of Nephrology and Hypertension, St Marianna University Hospital, Kawasaki, Japan
  • Sugaya, Takeshi, Division of Nephrology and Hypertension, St Marianna University Hospital, Kawasaki, Japan
  • Kimura, Kenjiro, Tokyo Takanawa Hospital, Tokyo, Japan
  • Shibagaki, Yugo, Division of Nephrology and Hypertension, St Marianna University Hospital, Kawasaki, Japan
  • Ikemori, Atsuko, Division of Nephrology and Hypertension, St Marianna University Hospital, Kawasaki, Japan
Background

Nuclear 1 factor related factor 2 (Nrf2) activator has an anti-oxidant effect and is expected to be a new strategy for chronic kidney disease. Urinary tubular marker, L-type fatty acid-binding protein (L-FABP), is known to accurately reflect tubular damage in a variety of renal stress, especially in oxidative stress. The aim of this study is to reveal the utility of urinary L-FABP as an indicator of the renoprotective effect of bardoxolne metyl (BM), a Nrf2 activator, in renal injury model due to oxidative stress.

Methods

We used an aldosterone (Ald)- and salt-induced renal injury model, in which oxidative stress is strongly associated with onset of tubulointerstitial damage. Tubulointerstitial damage with urinary L-FABP was evaluated using human L-FABP chromosomal transgenic (L-FABP+/-) male mice. Male L-FABP+/- mice were divided into three groups: The Ald group received systemic aldosterone infusions via an osmotic minipump and were given 1% NaCl water for 35 days. The Ald-Nrf2 group was given BM intraperitoneally in addition to an injection of aldosterone and salt. The dose of the Nrf2 activator was gradually increased every 7 days, reaching 10mg/kg/daily and continued for 14 days. The control group was only given a vehicle.

Results


The administration of BM significantly increased renal expression of the Nrf2 target antioxidant gene. Tubulointerstitial damage was significantly ameliorated in the Ald-BM group compared to the Ald group. The increase in reactive oxygen species in the kidneys of the Ald group was significantly prevented in the Ald-BM group. The upregulation of human L-FABP expression induced in the kidneys and the increase in urinary L-FABP in the Ald group were significantly suppressed by BM administration. The dynamics of L-FABP were significantly and strongly correlated with the prevention of the tubular damage (r=0.63), inflammatory infiltration(r=0.68) and fibrosis (r=0.72) by the administration of BM.

Conclusion

Urinary L-FABP is a useful marker reflecting the therapeutic efficacy of BM in Ald- and salt-induced renal injury.

Funding

  • NIDDK Support