Pirfenidone Suppressed the Development of Glomerulosclerosis in the FGS/Kist mouse

Abstract

Pirfenidone (PFD) is a newly developed anti-fibrotic agent. We evaluated the effect of PFD for the prevention of renal fibrosis using a spontaneous progressive glomerulosclerosis animal model, FGS/Kist mice. Male and female FGS/Kist mice were fed a diet containing 0.5% PFD or the same control diet (CD) without PFD, for 1, 2, or 3-month periods. Body weight was monitored for the general effect of PFD on the mice. Proteinuria and glomerular filtration rate (GFR) were evaluated for renal function. The sclerosis index was examined for the morphological changes. There were no significant changes in body weight between the PFD and control groups in both sexes. Proteinuria levels were low in all the PFD groups compared to the corresponding CD groups. The sclerosis scores were also reduced in both sexes of the 3-month PFD groups (p<0.05), and glomerular filtration rates were increased in both sexes of the 3-month PFD groups compared to the CD groups. The treatment of PFD for 1 or 2-month periods did not have statistic significances but the treatment for 3 months had statistic significances in sclerosis and GFR compared to CD groups. These results suggested that long-term administration of PFD suppressed the progression of glomerulosclerosis and improved renal function of the FGS/Kist mice.

Pirfenidone Is Renoprotective in Diabetic Kidney Disease

“…Previous reports of animal models of kidney disease demonstrated a consistent reduction of renal matrix accumulation with PFD but varying effects on proteinuria. [41][42][43] These data are important in interpreting clinical data from antifibrotic approaches. It is clearly conceptually possible to have effects to reduce mesangial matrix expansion and by inference protect the GFR, without necessarily reducing albuminuria.…”

Pirfenidone for Diabetic Nephropathy

“…There has been a growing interest in this drug to protect against various progressive fibrotic disorders. [31][32][33][34][35] The drug has been approved for clinical use in Japan for idiopathic pulmonary fibrosis. Two phase III studies of pirfenidone for idiopathic pulmonary fibrosis in North America, Europe, and Australia reported equivocal statistical outcomes but overall reduced disease severity.…”

The multifaceted role of pirfenidone and its novel targets

“…There was no significant difference between the PFD and control diet groups after treatment for 1 or 2 months, but there was a significant difference after treatment for 3 months, suggesting that long-term administration of PFD is required to suppress the progression of glomerulosclerosis and improve renal function in the FGS/Kist mice [64]. …”