SGLT2 inhibitor dapagliflozin protects the kidney in a murine model of Balkan nephropathy

Author:

Oe Yuji12,Kim Young Chul12ORCID,Sidorenko Viktoriya S.3ORCID,Zhang Haiyan4,Kanoo Sadhana2,Lopez Natalia2,Goodluck Helen A.2ORCID,Crespo-Masip Maria2,Vallon Volker12ORCID

Affiliation:

1. Department of Medicine, University of California-San Diego, La Jolla, California, United States

2. Veterans Affairs San Diego Healthcare System, San Diego, California, United States

3. Department of Pharmacological Sciences, Stony Brook University, Stony Brook, New York, United States

4. Department of Pathology, University of California-San Diego, San Diego, California, United States

Abstract

Recurrent exposure to aristolochic acid (AA) causes kidney function loss and fibrosis in mice and in humans, e.g., in the form of the endemic Balkan nephropathy. Inhibitors of the proximal tubule sodium-glucose transporter SGLT2 can protect against CKD progression, but their effect on AA-induced kidney injury remains unknown. Here we provide the first evidence in a murine model that pretreatment with an SGLT2 inhibitor can attenuate the AA-induced DNA damage response and subsequent nephropathy.

Funder

Laufer Family Foundation

HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases

HHS | NIH | National Institute on Aging

Manpei Suzuki Diabetes Foundation

U.S. Department of Veterans Affairs

Publisher

American Physiological Society

Subject

Physiology

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