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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 800 million people worldwide and 35 million people in the United States are living with CKD as of 2021. In other words, more than 1 in 8 adults worldwide are likely to have CKD. Whereas renin-angiotensin system (RAS) inhibitors are commonly used for the treatment of CKD, they have limited efficacy in slowing down the progression of CKD, leaving great unmet meidcal need.

Unmet 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 target the dysregulated cholesterol homeostasis and normalize it.

Mechanism of action

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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, cholesterol metabolism modulators (CMMs) have shown to help clearance of cholesterol in the kidney and exert renoprotective effects, in part by upregulating ABCA-1 in the kidney. RN-005, Renatus's proprietary CMM, has shown promising effects in upregulating ABCA-1 and normalizing cholesterol homeostasis in the kidney. Such regulation of cholesterol metabolism effectively protected the kidney as shown by reduced blood creatinine, albuminuria, and fibrosis. Overall, the results suggest that CMMs can provide a novel and effective modality for treating chronic kidney disease via cholesterol metabolism modulation.

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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