Therapeutic Potential of Pirfenidone in Adenine-Induced Chronic Kidney Disease: An Integrated Experimental and In Silico Study.

Chronic kidney disease (CKD) is a progressive condition characterized by sustained loss of renal function, frequently accompanied by fibrosis and oxidative stress-mediated damage. In this study, adenine-induced CKD was used as an experimental model to assess the effects of pirfenidone. Rats fed a 0.75% adenine diet exhibited key features of renal dysfunction, including reduced body weight, kidney hypertrophy, elevated serum urea and creatinine, decreased creatinine clearance, polyuria, low urine osmolarity, increased urinary N-acetylglucosaminidase excretion, and reduced antioxidant activity. Pirfenidone at 200 mg/kg and 500 mg/kg improved several of these parameters, with the higher dose showing greater efficacy. This approach identified 14 overlapping genes associated with the predicted targets of pirfenidone and with those implicated in CKD. The genes were involved in fibrotic and immunoregulatory pathways responsible for extracellular matrix turnover, with TIMP-1 as the most central gene within the interactive network. Docking studies further indicated a likely interaction between pirfenidone and TIMP-1, with an estimated binding energy of - 6.43 kcal/mol and support from specific interactions, including hydrogen bonding with Ser100 as well as hydrophobic and polar contacts. These observations suggest that pirfenidone may support kidney function not only by improving biochemical and functional parameters but also by interacting with molecular components associated with disease progression.