Pirfenidone prevents acute kidney injury in the rat

Ixchel Lima-Posada,Norma A Bobadilla,Nathan Berman-Parks,Rosalba Pérez-Villalva,Francesco Fontana

doi:10.1186/s12882-019-1364-4

Ixchel Lima-Posada, Norma A Bobadilla + Show 3 more

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BackgroundPirfenidone 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.MethodsEighteen 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.ResultsAs 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 (UNO2/NO3V). In the I/R + PFN group, recovery of renal function and UNO2/NO3V was observed, together with lesser histological signs of tubular injury compared to the I/R group.ConclusionsThis 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.

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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 and possesses antioxidant and anti-inflammatory properties
The mean body weight (BW) was slightly higher in the Ischemia reperfusión (I/R) group, but this increase was according to initial body weight that was slightly higher (Fig. 1a and b)
The renal injury induced by I/R was evidenced by the significant reduction in renal blood flow and creatinine clearance, together with a significant elevation of BUN, compared to the sham group

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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 and possesses antioxidant and anti-inflammatory properties. We assessed the effect of prophylactic administration of pirfenidone on acute kidney injury due to bilateral renal ischemia. Acute kidney injury (AKI) affects 21% of hospitalized patients, and the incidence is higher in the intensive care unit (60%) [1]. AKI is often caused by a reduction in renal blood flow (RBF) that induces endothelial and tubular epithelial damage [3,4,5,6,7]. The reduced RBF causes a decrease in the perfusion of the peri-tubular capillaries, injuring the S2 and S3 segments of the Endothelial cells undergo several alterations, such as loss of their intercellular junctions, alterations in the cytoskeleton and endothelial glycocalyx, increased permeability of the microcirculation and interstitial edema. There is an increase in the expression of adhesion molecules that allow inflammatory cells to adhere to the endothelium, with consequent leukocyte infiltration in the renal interstitium [14]

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