The farnesoid X receptor agonist EDP‐305 reduces interstitial renal fibrosis in a mouse model of unilateral ureteral obstruction

What is it about?

End stage renal disease (ESRD) is the last stage of chronic kidney disease. At this point, the kidney can no longer support the body's needs to excrete harmful toxins. Patients with ESRD will require dialysis or a kidney transplant to stay alive. ESRD is an enormous burden to the health care system as well. Pathologically, ESRD is characterized by the replacement of normal functional kidney structures with dense non-functioning fibrotic tissue. A potential strategy for halting or slowing down the progression of chronic kidney disease to ESRD is by reducing the deposition of collagen or the process of fibrosis. In this project, we targeted a specific receptor, Farnesoid X receptor (FXR), and its effects on fibrosis. FXR agonism is known to reduce liver fibrosis, but its effects on kidney fibrosis is still relatively unknown. We created a rapid form of kidney fibrosis in mice, by interrupting urine drainage. After completion interruption of the kidney drainage system, we initiated treatment with FXR agonist, EDP-305 at two separate doses, 10mg and 30mg. We found that after 14 days, there was significant reduction in collagen deposition. Treatment with EDP-305 resulted in a reduction of inflammation, collagen deposition, and ultimately resulted in preservation of the normal renal architecture.

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