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CHRONIC KIDNEY DISEASE

Chronic kidney disease (CKD) is a long-term condition where the kidneys don't work as well as they should. More than 35 million people are living with CKD in the United States as of 2021. Common causes of CKD include high blood pressure, diabetes, high cholesterol, infection, long-term use of certain medicines, and others. 

Medical needs

Mounting evidence suggests that accumulation of cholesterol in the kidney can cause pathogenesis and progression of kidney disease. Dysregulated cholesterol homeostasis is observed in prevalent (e.g., diabetic kidney disease), as well as in less prevalent (e.g., focal segmental glomerulosclerosis and Alport syndrome) renal diseases. However, there is no treatment that can directly mediate cholesterol efflux within the kidney.

Mechanism of action

MoA kidney_edited.png

In various disease models including diabetic kidney disease, focal segmental glomerulosclerosis, and Alport syndrome, downregulation of ATP-binding cassette transporter (ABCA-1)-mediated cholesterol efflux was observed. In the aforementioned models, cyclodextrin has shown to help clearance of cholesterol in the kidney and exert renoprotective effects, in part by upregulating ABCA-1 in the kidney. RN-005 has shown promising effects in upregulating ABCA-1 in kidney cells.

References

- Cyclodextrin Protects Podocytes in Diabetic Kidney Disease (Diabetes, 2013)

- Local TNF causes NFATc1-dependent cholesterol-mediated podocyte injury (Journal of Clinical Investigation, 2016)

- Hydroxypropyl-
β-cyclodextrin protects from kidney disease in experimental Alport syndrome
and focal segmental glomerulosclerosis (Kidney International, 2018)

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