Pirfenidone prevents acute kidney injury in the rat

BACKGROUND: Pirfenidone is an orally active drug used for the treatment of idiopathic pulmonary fibrosis to slow loss of lung function; it acts mainly through an antifibrotic effect but also possesses antioxidant and anti-inflammatory properties. We assessed the effect of prophylactic administration of pirfenidone on acute kidney injury due to bilateral renal ischemia. METHODS: Eighteen rats were included and divided in: 1) sham-operated rats (S), 2) rats underwent bilateral renal ischemia for 20 min (I/R), and 3) rats treated with pirfenidone 700 mg/kg/day 24 h before surgery and subjected to bilateral renal ischemia for 20 min (I/R + PFN). All the rats were euthanized and studied 24 h after renal reperfusion. RESULTS: As was expected, the I/R group exhibited a significant reduction in creatinine clearance, urinary output and renal blood flow, as well as extensive tubular injury. These alterations were associated with a significant decrease in urinary excretion of nitrites and nitrates (UNO(2)/NO(3)V). In the I/R + PFN group, recovery of renal function and UNO(2)/NO(3)V was observed, together with lesser histological signs of tubular injury compared to the I/R group. CONCLUSIONS: This study shows that prophylactic administration of pirfenidone prevented acute kidney injury due to bilateral ischemia in the rat. Recovery of NO production appears to be one of the mechanism of pirfenidone renoprotective effect. Our findings suggest that pirfenidone is a promising drug to reduce renal injury induced by I/R.