Kidney Week

Abstract: SA-PO310

Intervention with the Novel Fibrokinase Inhibitor ANG3070 Mitigates Glomerular Scarring and Attenuates Proteinuria in a Model of Focal Segmental Glomerulosclerosis

Session Information

• Cellular Crosstalk in Glomerular Diseases - II
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1201 Glomerular Diseases: Fibrosis and Extracellular Matrix

Authors

• Narayan, Prakash, Angion Biomedica Corp, Uniondale, New York, United States

Prakash Narayan,

• Ali, Quaisar, Angion Biomedica Corp., Uniondale, New York, United States

Quaisar Ali,

• Paka, Latha, Angion Biomedica Corp, Uniondale, New York, United States

Latha Paka,

• Li, Jingsong, Angion Biomedica Corp., Uniondale, New York, United States

Jingsong Li,

• Dana, Dibyendu, Angion Biomedica Corp., Uniondale, New York, United States

Dibyendu Dana,

• Gadhiya, Satishkumar V., Angion Biomedica Corp., Uniondale, New York, United States

Satishkumar V. Gadhiya,

• Li, An-Hu, Angion Biomedica Corp., Uniondale, New York, United States

An-Hu Li,

• Yamin, Michael A., Angion Biomedica Corp., Uniondale, New York, United States

Michael A. Yamin,

• Goldberg, Itzhak D., Angion Biomedica Corp., Uniondale, New York, United States

Itzhak D. Goldberg,

Background

Steroid-resistant (SR) primary Focal Segmental Glomerulosclerosis (FSGS) is accompanied by nephrotic-range proteinuria and necessitates renal replacement therapy. We investigated the effects of a novel small molecule platelet-derived growth factor (PDGF) receptor + vascular endothelial growth factor (VEGF) receptor inhibitor, ANG3070, in a clinically relevant model of FSGS.

Methods

Adult male rats were administered puromycin ((puro), 100 mg/kg, intraperitoneal) or saline (sham). On day 3, after onset of proteinuria, the puro cohort was randomized to vehicle or ANG3070. Twenty-four hour urine was collected on days 7 and 14 at which kidneys were retrieved for analysis.

Results

Puro administration was associated with accumulation of PDGF in the glomerulus, increased glomerular dimension and scarring, and proteinuria. Intervention with ANG3070 attenuated proteinuria on days 7 and 14. Puro-induced glomerular hypertrophy and scarring were both reduced with ANG3070 intervention. Proteinuria-induced tubular toxicity was also reduced with drug.

Conclusion

In a clinically relevant model of FSGS, intervention with ANG3070 is beneficial. These data, form, in part, the basis for using a Precision Medicine approach to evaluate safety and efficacy of this drug in SR primary FSGS.