Pirfenidone improves renal function and fibrosis in the post-obstructed kidney

Shimizu, Tetsuji; Kuroda, Takayuki; Hata, Satoshi; Fukagawa, Masafumi; Margolin, Solomon B.; Kurokawa, Kiyoshi

doi:10.1046/j.1523-1755.1998.00962.x

Cited by 145 publications

(95 citation statements)

References 34 publications

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“…In our study, there was an improvement in GFR, though with a predominant effect on collagen within the interstitium and tubules, and less so on glomerular lesions. This bears some similarity to recent studies of pirfenidone treatment in fibrotic kidney diseases such as the post-obstructive kidney model (42) and chronic cyclosporine nephrotoxicity (43). In these studies, pirfenidone treatment improved reduced the histologic severity of disease, and reduced collagen content within the kidney.…”

Section: Discussionsupporting

confidence: 78%

Inhibition of Prolyl-4-Hydroxylase Ameliorates Chronic Rejection of Mouse Kidney Allografts

Franceschini

Cheng

Zhang

et al. 2003

American Journal of Transplantation

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Section: Discussionsupporting

confidence: 78%

Inhibition of Prolyl-4-Hydroxylase Ameliorates Chronic Rejection of Mouse Kidney Allografts

Franceschini

Cheng

Zhang

et al. 2003

American Journal of Transplantation

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“…Recent research has demonstrated that various cytokines and chemokines including TGF-b, TNF-a, and ICAM-1 are involved in renal fibrosis induced by UUO. 27,29,30 Our study also showed that ICAM-1 and TNF-a mRNA expression was upregulated in the UUO group. Furthermore, treatment with RSV markedly decreased these mRNA levels.…”

Section: Discussionsupporting

confidence: 67%

“…26 A previous study has shown that TGF-b levels increased from day 3 after UUO surgery. 27 Similarly, we also found that TGF-b mRNA expression was significantly elevated in the UUO group. However, treatment with RSV significantly decreased TGF-b expression.…”

Section: Discussionsupporting

confidence: 64%

Resveratrol as a therapeutic agent for renal fibrosis induced by unilateral ureteral obstruction

et al. 2013

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Aims: Renal fibrosis is a common outcome of chronic kidney disease. This study was designed to examine the protective effects of resveratrol (RSV) against renal fibrosis induced by unilateral ureteral obstruction (UUO). We also attempted to elucidate the potential mechanism involved. Methods: Mice were randomly divided into three groups: sham-operated, UUO, and UUO/RSV (20 mgÁkg À1 Áday À1). Histological changes were examined using periodic acid-Schiff and Masson's trichrome staining after 14 days. Superoxide dismutase (SOD), malondialdehyde (MDA), and 8-OHdG levels were determined using a commercially available kit. ICAM-1, TNF-a, and TGF-b levels were measured using real-time PCR. Fibronectin levels were measured by western blot, and the Smad3 acetylation and Sirt1 were examined by immunoprecipitation and western blot. Results: Our study showed that RSV treatment significantly attenuated renal injury including extracellular matrix deposition and tubulointerstitium damage. Renal cortical mRNA levels of ICAM-1, TNF-a, and TGF-b, protein expression of fibronectin and Smad3 acetylation were significantly upregulated in the UUO group. However, treatment with RSV significantly decreased the expression of these proteins. Furthermore, RSV also decreased the levels of reactive oxygen species (ROS) including MDA and 8-OHdG, and increased the level of SOD, which protects cells against ROS damage. Conclusion: Our findings suggest that RSV treatment inhibits oxidative stress, Smad3 acetylation, and renal interstitial fibrosis. Therefore, RSV may have potential as a therapeutic target for the treatment of chronic kidney disease.

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“…Pirfenidone reduces fibrosis and prevents loss of glomerular filtration in animal models of renal disease (9 -14). In the five-sixths nephrectomy rat model of postadaptive FSGS, pirfenidone treatment for 12 wk attenuates the accumulation of glomerular matrix protein, the expression of glomerular TGF-␤, and the loss of glomerular filtration (14,15). Clinical trials that have evaluated safety and efficacy of pirfenidone in various fibrotic diseases have also been encouraging.…”

mentioning

confidence: 99%

Pirfenidone Slows Renal Function Decline in Patients with Focal Segmental Glomerulosclerosis

Cho¹,

Smith²,

Branton³

et al. 2007

Clinical Journal of the American Society of Nephrology

188

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Background and Objectives: Pirfenidone is an orally available antifibrotic agent that has shown benefit in animal models of pulmonary and renal fibrosis and in clinical trials of pulmonary fibrosis, multiple sclerosis, and hepatic cirrhosis. Our objective was to determine whether pirfenidone slows the loss of renal function in focal segmental glomerulosclerosis.Design, Setting, Participants, & Measurements: An open-label trial was performed to evaluate the safety and efficacy of pirfenidone in patients with idiopathic and postadaptive focal segmental glomerulosclerosis. The monthly change in estimated GFR, expressed as ml/min per 1.73 m 2 , was compared between the baseline period and the treatment period. During both periods, patients received angiotensin antagonist therapy if tolerated. Twenty-one patients were enrolled, and 18 patients completed a median of 13 mo of pirfenidone treatment.Results: The monthly change in GFR improved from a median of ؊0.61 ml/min per 1.73 m 2 (interquartile range ؊1.31 to ؊0.41) during the baseline period to ؊0.45 ml/min per 1.73 m 2 (interquartile range ؊0.78 to ؊0.16) with pirfenidone therapy. This change represents a median of 25% improvement in the rate of decline (P < 0.01). Pirfenidone had no effect on BP or proteinuria. Adverse events attributed to therapy included dyspepsia, sedation, and photosensitive dermatitis.Conclusions: It is concluded that pirfenidone is an attractive candidate for placebo-controlled trials in patients with progressive chronic kidney disease.

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Pirfenidone improves renal function and fibrosis in the post-obstructed kidney

Abstract: These results demonstrate that PFD can attenuate both renal fibrosis and renal damage in this model, and suggest that PFD can be clinically useful for preventing progressive, irreversible renal failure.

Cited by 145 publications

References 34 publications

Inhibition of Prolyl-4-Hydroxylase Ameliorates Chronic Rejection of Mouse Kidney Allografts

Inhibition of Prolyl-4-Hydroxylase Ameliorates Chronic Rejection of Mouse Kidney Allografts

Resveratrol as a therapeutic agent for renal fibrosis induced by unilateral ureteral obstruction

Pirfenidone Slows Renal Function Decline in Patients with Focal Segmental Glomerulosclerosis

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