Executive Summary : | Chronic kidney disease (CKD) is a global pandemic with over 800 million patients, with 1-13% of the Indian population suffering from the disease. The pathophysiology of CKD is complex, with various pathomechanisms involved in its progression. Early stages involve decreased renal blood flow, oxidative stress, ischemic injury, and overactivation of the ET-1A receptor, which increases low-grade inflammation and affects kidney functions. Kidney fibrosis further initiates vascular calcification, leading to kidney failure. To improve kidney function during early and later stages of CKD, improving renal blood flow, inhibition of ET-1A, and prevention of vascular calcification could be beneficial. However, available therapeutic options are not uniformly effective. Repurposing approved drugs can reduce costs and time required for drug development, and their known safety profiles make them more suitable for use against CKD. To evaluate three clinically approved drugs, the researchers plan to use Wistar rats and NRK52E cells for in vivo and in vitro experiments. They will identify and screen potential therapeutic targets involved in the progression of CKD using network pharmacology. The in vitro CKD model will be developed and validated, and future experiments will include biochemical analysis, histology, western blotting, immunohistochemistry, IF, flow cytometry, and other relevant studies. This repurposing approach will reveal the underlying molecular mechanisms through which these drugs exert renoprotective action, providing preclinical knowledge for further clinical studies. |