Bardoxolone: a new potential therapeutic agent in the treatment of autosomal dominant polycystic kidney disease?

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of chronic renal failure. The natural history of ADPKD is characterized by development of multiple bilateral renal cysts that progressively destroy the architecture of the parenchyma and lead to an enlargement in the total kidney volume (TKV) and to the decline of the renal function. Cyst growth activates the immune system response causing interstitial inflammation and fibrosis that contribute to disease progression. In recent years, the therapeutic toolkit available to the nephrologist in the treatment of ADPKD has been enriched with new tools, and in this context bardoxolone is classified as a potential therapeutic agent. It is a semisynthetic derivative of triterpenoids, a family of compounds widely used in traditional Asian medicine for their multiple effects. Bardoxolone exerts antioxidant activity by promoting the activation of Nrf2 (Nuclear factor erythroid2-derivative – 2) and the downregulation of the proinflammatory NF-kB (Nuclear factor kappa-light-chain-enhancer of activated B cells) signaling. Several pieces of evidence support the use of bardoxolone in the treatment of chronic kidney disease (CKD) documenting an effect on the increase of glomerular filtration rate (GFR). However, its use is limited to patients at risk of heart failure. The FALCON study will clarify the efficacy and safety of bardoxolone in the treatment of ADPKD.


Keywords:
polycystic kidney disease, inflammation, bardoxolone, glomerular filtration

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Introduzione

La malattia del rene policistico autosomico dominante (ADPKD) è la più frequente nefropatia geneticamente trasmessa [12]. Si tratta di un disordine monogenico in cui sono state identificate mutazioni a carico di tre geni coinvolti: PKD1 (78% dei casi), PKD2 (15% dei casi) e GANAB (circa 0.3% dei casi) [3].  

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