Small molecule urea transporter (UT) inhibitors to treat or prevent conditions associated with chronic kidney disease.
- Provides a cardio-protective benefit in CKD patients.
- Suppresses cardiac hypertrophy and fibrosis.
Cardiovascular complications commonly occur in patients with chronic kidney disease (CKD). Uremic cardiomyopathy is a complication of CKD and is characterized by hypertension, cardiac hypertrophy, fibrosis, and hypervolemia. Current treatments for cardiomyopathy in CKD patients include antihypertensive drugs and diuretics, such as ACE inhibitors, furosemide, or Ca2+ channel blockers. However, these therapies are reported to have insufficient benefit or harmful side effects. Urea plays a major role in the urine concentrating mechanism. Urea Transporter (UT) proteins transport urea. UT-A and UT-B genes are expressed throughout the urinary tract and an inhibition of UT may be useful to prevent volume overload, which could result in positive cardiac effects.
Emory researchers have investigated a new class of diuretics, named “ureraretics.” This small molecule inhibits urea transporter (UT)-A to prevent uremic cardiomyopathy. In the study of CDK mice treated with dimethylthiourea (DTMU), the researchers found that inhibition of UT reduced renin and angiotensin-converting enzyme (ACE), as well as suppressed vimentin amount. They have shown that UT inhibition may be an effective treatment to reduce hypertension, cardiac fibrosis, and improve heart function. Other diuretics may show similar results in treating cardiomyopathies in CKD patients.
Studies completed in CKD mice models.
Publications: Kuma, A. et al. (2020). The FASEB Journal, 34(6), 8296-8309.