Potential Add-On Benefits of Dietary Intervention in the Treatment of Autosomal Dominant Polycystic Kidney Disease

Author:

Rosati Erica12ORCID,Condello Giulia12,Tacente Chiara12,Mariani Ilaria12ORCID,Tommolini Valeria12,Calvaruso Luca12ORCID,Fulignati Pierluigi12,Grandaliano Giuseppe12,Pesce Francesco3ORCID

Affiliation:

1. Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, 00168 Rome, Italy

2. Unità Operativa Complessa di Nefrologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy

3. Division of Renal Medicine, Ospedale Isola Tiberina—Gemelli Isola, 00186 Rome, Italy

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited cause of renal failure. The pathogenesis of the disease encompasses several pathways and metabolic alterations, including the hyperactivation of mTOR and suppression of AMPK signaling pathways, as well as mitochondrial dysfunction. This metabolic reprogramming makes epithelial cyst-lining cells highly dependent on glucose for energy and unable to oxidize fatty acids. Evidence suggests that high-carbohydrate diets may worsen the progression of ADPKD, providing the rationale for treating ADPKD patients with calorie restriction and, in particular, with ketogenic dietary interventions, already used for other purposes such as in overweight/obese patients or in the treatment of refractory epilepsy in children. Preclinical studies have demonstrated that calorie restriction may prevent and/or slow disease progression by inducing ketosis, particularly through increased beta-hydroxybutyrate (BHB) levels, which may modulate the metabolic signaling pathways altered in ADKPK. In these patients, although limited, ketogenic intervention studies have shown promising beneficial effects. However, larger and longer randomized controlled trials are needed to confirm their tolerability and safety in long-term maintenance and their additive role in the therapy of polycystic kidney disease.

Publisher

MDPI AG

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