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-PO127

Soluble fms-Like Tyrosine Kinase-1 Promotes AKI and CKD After Renal Ischemia-Reperfusion Injury

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Tsushima, Hideo, Nara Medical University, Kasihara-city, Japan
  • Eriguchi, Masahiro, Nara Medical University, Kasihara-city, Japan
  • Matsui, Masaru, Nara Prefecture General Medical Center, Nara, NARA, Japan
  • Kosugi, Takaaki, Nara Medical University, Kasihara-city, Japan
  • Nishimoto, Masatoshi, Nara Medical University, Kasihara-city, Japan
  • Tanabe, Kaori, Nara Medical University, Kasihara-city, Japan
  • Tagawa, Miho, Nara Medical University, Kasihara-city, Japan
  • Samejima, Ken-ichi, Nara Medical University, Kasihara-city, Japan
  • Tsuruya, Kazuhiko, Nara Medical University, Kasihara-city, Japan
Background

Soluble fms-like tyrosine kinase-1 (sFlt-1), which is extracellular domains of Flt-1, acts as an antagonist of both placental growth factor (PlGF) and vascular endothelial growth factor A (VEGF-A). We previously reported that kidney is a main source of circulating sFlt-1 (about 50%). Generally, VEGF signaling is associated with angiogenesis and macrophage migration. Angiogenesis has a protective effect against renal ischemia, however macrophage migration contributes renal injury. The objective of this study is to examine the role of sFlt-1 in acute and chronic kidney injury after renal ischemia.

Methods

Unilateral or bilateral 30-minute renal ischemia were performed using sFlt-1 knockout (KO) and wild-type (WT) mice. For evaluation of acute kidney injury (AKI), plasma urea nitrogen levels and macrophage infiltration in the kidney were measured on day 1 and 7 after bilateral renal ischemia. Kidneys two weeks after unilateral renal ischemia were used for chronic kidney disease (CKD) model. Ischemic/non-ischemic kidney weight ratios (ischemic kidney weight divided by non-ischemic kidney weight) and renal fibrosis of the unilateral ischemic kidneys (Sirius red staining) were examined.

Results

After bilateral renal ischemia, plasma urea nitrogen levels from sFlt-1 KO mice were significantly lower than those from WT mice (130.5 ± 5.0 vs 164.0 ± 10.2 mg/dL, p=0.009 on day 1; 56.2 ± 2.9 vs 76.3 ± 4.1 mg/dL, p=0.001 on day 7). However, there was no difference in macrophage infiltration in the kidneys between sFlt-1 KO and WT mice on day 1 (49 ± 8 vs 59 ± 5/field, p=0.30). Two weeks after unilateral renal ischemia, ischemic/non-ischemic kidney weight ratios from sFlt-1 KO mice were significantly larger than those from WT mice (76.5 ± 7.6 vs 60.4 ± 1.9%; P=0.046). Finally, renal fibrosis from sFlt-1 KO mice was significantly reduced by 21.0% compared to WT mice (p=0.032).

Conclusion

sFlt-1, which is mainly secreted from kidneys, promotes AKI and following CKD after renal ischemia-reperfusion injury in a paracrine manner.