Pirfenidone: an anti-fibrotic therapy for progressive kidney disease

Abstract

Importance of the field: Many chronic diseases of various etiologies lead to fibrosis and organ dysfunction. Despite many advances in medicine in recent years, options to slow the progression of fibrotic diseases have remained limited. The recent availability of pirfenidone, an antifibrotic and anti-inflammatory investigational agent, thus offers a new hope for treating progressive fibrotic diseases.

Areas covered in this review: This review provides concise review of the available data regarding the mechanism and pharmacokinetics of pirfenidone and preclinical and clinical data regarding efficacy and safety in fibrotic diseases of the kidney. It also reviews results of clinical trials involving pirfenidone in other fibrotic diseases.

What the reader will gain: The review will provide in-depth review of pirfenidone with a renal focus.

Take home message: Because many of the available clinical trials have been small and/or uncontrolled, conclusive evidence regarding efficacy and safety of pirfenidone is lacking, particularly in patients with renal or hepatic dysfunction. Larger studies are needed to better understand long-term efficacy and safety of this medication in various patient populations.

Figure 1. Mechanisms of progressive kidney injury

Tissue injury is initiated by genetic factors (e.g sickle cell anemia) or environmental factors (e.g. viral infection) or most frequently by diseases arising out of a combination of both processes (e.g hypertension, diabetes, coronary heart disease). The figure illustrates some pathways for kidney injury but similar processes affect every tissue. Tissue injury, often involving inflammation, leads to the twin processes of fibrogenesis and cellular injury, which interact as shown. Ultimately, organs fail because cells and the tissue as a whole can no longer fulfill critical organ functions. It is likely that successful therapeutic strategies to slow and perhaps reverse organ failure will be those that limit and reverse fibrogenesis and stabilize differentiate cell phenotypes.