Abstract: SA-PO344

Therapeutic Activity of the Novel Kinase Inhibitor ANG3070 in Models of Renal Scarring Accompanied by Co-Morbidities

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 308 CKD: Mechanisms of Tubulointerstitial Fibrosis

Authors

  • Narayan, Prakash, Angion Biomedica Corp, Uniondale, New York, United States
  • Duan, Bin, Angion Biomedica Corp, Uniondale, New York, United States
  • Zhou, Ping, Angion Biomedica Corp, Uniondale, New York, United States
  • Paka, Latha, Angion Biomedica Corp, Uniondale, New York, United States
  • Yamin, Michael A., Angion Biomedica Corp., Uniondale, New York, United States
  • Goldberg, Itzhak D., Angion Biomedica Corp., Uniondale, New York, United States
Background

Chronic kidney disease (CKD), characterized by extracellular matrix deposition in the renal interstitium, is driven, in part by aberrant receptor tyrosine kinase signaling. We investigated the effects of a novel small molecule receptor tyrosine kinase inhibitor, ANG3070, in clinically relevant models of CKD accompanied by co-morbidities.

Methods

Approximately 18 month old male Fischer 344 rats were subjected to 5/6 nephrectomy (or sham surgery) to model CKD in middle-aged patients. Following onset of renal disease, animals were randomized to vehicle or ANG3070 (various doses, PO, BID). In order to model CKD in the setting of metabolic syndrome, ~8 week old, obese, male, ZSF1 rats were subjected to 5/6 nephrectomy, and following onset of renal disease, randomized to vehicle or ANG3070 (various doses, PO, BID). In both models, after 8 weeks of drug treatment, a comprehensive panel of renal functional and histological endpoints was evaluated to assess the effects of ANG3070.


Results

Intervention with ANG3070 in aged rats with CKD, reduced albuminuria and attenuated several indices of renal scarring including kidney hydroxyproline content, α-smooth muscle actin expression and collagen (picosirius red staining). Intervention with ANG3070 in the rat model of metabolic syndrome and CKD was associated with reduced kidney hydroxyproline content, α-smooth muscle actin expression and collagen (Masson’s trichrome and picosirius red staining).

Conclusion

In clinically relevant models of renal scarring, intervention with the novel receptor tyrosine kinase inhibitor ANG3070 is beneficial.

Funding

  • Other U.S. Government Support