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Kidney Week

Abstract: FR-PO718

2-Deoxy-D-Glucose Effectively Retards Kidney and Liver Cysts Growth in the Mouse at a Plasma Concentration That Is Safe in Humans: A Bridge Study to Design a First Safety Trial in ADPKD Patients

Session Information

Category: Genetic Diseases of the Kidneys

  • 1001 Genetic Diseases of the Kidneys: Cystic


  • Chiaravalli, Marco, San Raffaele Scientific Institute, Milano, Italy
  • Canu, Tamara Patrizia, San Raffaele Scientific Institute, Milano, Italy
  • Armirotti, Andrea, Istituto Italiano di Tecnologia, Genova, Italy
  • Esposito, Antonio, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, Milan, Italy
  • Fermo, Isabella, San Raffaele Scientific Institute, Milano, Italy
  • Reggiani, Angelo M., Istituto Italiano di Tecnologia, Genova, Italy
  • Boletta, Alessandra, San Raffaele Scientific Institute, Milano, Italy

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a genetic disorder characterized by renal and liver cysts. The first therapy, tolvaptan, was recently approved. However, the presence of side effects and low tolerability calls for development of alternative approaches. We previously showed that inhibition of glycolysis by 2-deoxy-glucose (2DG) significantly retards disease progression (Rowe et al Nat Med, 2013; Chiaravalli et al, JASN, 2016). To translate the results for application in humans, we studied long term oral administration of 2DG and precise pharmacokinetic (PK) parameters.


We used a slowly progressive murine model by inactivating Pkd1 at P45 (Pkd1flox/-TmCre). Cohorts of 13 mice were treated for 4.5 months with oral administration of 2DG (100mg/kg) daily, for 5 days a week followed by 2 days of washout. Total kidney volume (TKV) was monitored by MRI, renal function by blood urea nitrogen and creatinine. At sacrifice kidney/body weight and histological analysis were performed. Liver cysts were identified by Cytokeratin-19 staining. Body weight, water and food intake as well as serum levels of ALT, AST, ALB and CK were detected for safety analysis. For the PK study of 2DG blood was collected after gavage at different time points (15, 30, 45, 60, 120, 180 min, 12 h, 24 h) and detected with HPLC pre-column fluorescent derivatization.


100mg/kg of 2DG significantly reduces TKV and restores renal function in the Pkd1flox/-TmCre mice. Biliary cysts were significantly reduced in number, length and area after 2DG treatment (n=8). Importantly, no sign of toxicity can be detected neither in Pkd1flox/- TmCre-nor in wt mice. PK analysis revealed that 100mg/kg 2DG oral administration in mice corresponds to/is slightly lower than the dose of 30mg/kg in humans based on published studies, a dosage extensively shown to be safe with no adverse events reported.


Our data show that 2DG is efficacious on renal and liver cysts, it improves renal function and shows no signs of toxicity at a dose that corresponds to a well tolerated dose in humans. Our data build a strong rationale for designing a first study with 2DG in ADPKD patients.


  • Private Foundation Support