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Chronic kidney disease (CKD) is characterized by progressive loss of kidney function. Several factors contribute to its development, including clinical conditions such as hypertension and diabetes. After an initial insult, disease progression is characterized by changes in renal hemodynamics and local inflammation, resulting in tissue fibrosis. Therefore, the participation of cellular and inflammatory mechanisms in the process has been intensely investigated. The lack of an effective treatment to slow CKD progression or reverse the established damage led to the search for new strategies. In this context, pirfenidone, an anti-fibrotic drug that acts to prevent collagen deposition have demonstrated great potential in experimental models of fibrosis. Considering the importance of the fibrogenesis in the context of CKD progression, the present study aimed to analyze the potential renoprotective effect of pirfenidone, in an experimental model of hypertensive nephrosclerosis.
Chronic nephropathy was induced in rats by the nitric oxide synthesis inhibition, obtained by the oral administration of 70 mg/kg/day of L-NAME (NAME), diluted in drinking water, associated to a 3% high sodium (HS) diet. Animals were divided among 4 groups; NAME: kept untreated, LOS: NAME rats treated with 50mg/Kg/d of losartan, PIRF: NAME rats treated with 750mg/Kg/d, and Control: animals which received only the HS diet, with no further drugs or treatments. Animals were followed for 30 days, when systolic blood pressure (SBP), 24h urinary albumin excretion (UAE), glomerulosclerosis (GS), glomerular ischemia (GI), interstitial fibrosis (INT), infiltration by macrophages (CD68) and T-cells, cell proliferation (PCNA), as well as renal cortical interstitial a-SMA, collagen I and fibronectin accumulation, were evaluated.
Detailed results were presented as Mean ± SE in the attached table. Differences among groups were analyzed by one-way ANOVA: p<0.05 vs. *Control, #NAME, &LOS.
The present results showed that pirfenidone was as effective as losartan in lowering CKD progression. This drug exhibited marked renoprotective effects, significantly reducing renal infiltration of inflammatory cells and drastically abrogated renal fibrosis, representing an important therapeutic alternative for the treatment of CKD.