Pirfenidone treatment attenuates fibrosis in autosomal dominant polycystic kidney disease.

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the formation of fluid filled cysts, progressive fibrosis and chronic inflammation, often leading to kidney failure. Renal fibrosis in ADPKD is primarily driven by myofibroblast activation and excessive extracellular matrix (ECM) accumulation, which contribute to disease progression. Here we investigated the therapeutic potential of pirfenidone, an antifibrotic drug, on myofibroblast activity, ECM production, and ADPKD progression. Methods: Primary cultures of myofibroblasts from human ADPKD kidneys were treated with pirfenidone Results: Analysis of single-nucleus RNA sequencing data of human ADPKD kidneys revealed that fibroblasts are a primary source of fibrous and cell-adhesive ECM, with higher ECM gene expression compared to normal human kidneys. Treatment of human ADPKD renal myofibroblasts with pirfenidone led to reduced ECM gene expression, cell proliferation, migration and contractility. Conclusion: These findings suggest that pirfenidone mitigates renal fibrosis and preserves renal architecture in ADPKD, supporting its potential as a therapeutic strategy to inhibit fibrosis in ADPKD.