Kidney Week

Abstract: TH-PO442

Early Insights from Grease II: Safety and Efficacy of a Ketogenic Diet in ADPKD

Session Information

• Cystic Kidney Diseases: Clinical Assessment and Therapeutic Directions
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1201 Genetic Diseases of the Kidneys: Cystic

Authors

• Ferri, Maria, AOU Policlinico di Modena, Nephrology Unit, Modena, Italy

Maria Ferri, MD

• Pezzuoli, Carla, Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy

Carla Pezzuoli

• Ligabue, Giulia, University of Modena and Reggio Emilia, Dep. CHIMOMO,, Modena, Italy

Giulia Ligabue, PhD

• Giovanella, Silvia, University of Modena and Reggio Emilia, Dep. CHIMOMO,, Modena, Italy

Silvia Giovanella, MS

• Testa, Francesca, AOU Policlinico di Modena, Nephrology Unit, Modena, Italy

Francesca Testa, MD

• Ferrarini, Marco, University of Modena and Reggio Emilia, Dep. CHIMOMO,, Modena, Italy

Marco Ferrarini

• Ciurli, Francesca, Nephrology, Dialysis and Kidney Transplant Unit, IRCCS, AOU, Bologna, Italy

Francesca Ciurli, MD

• Amicone, Maria, AOU Federico II, Nephrology Unit,, Napoli, Italy

Maria Amicone, MD, PhD

• Pisani, Antonio, AOU Federico II, Nephrology Unit,, Napoli, Italy

Antonio Pisani, MD, PhD

• Magistroni, Riccardo, University of Modena and Reggio Emilia, Dep. CHIMOMO,, Modena, Italy

Riccardo Magistroni, MD

Group or Team Name

• AOU Policlinico di Modena, Nephrology Unit.

Background

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a systemic disorder marked by the progressive formation and enlargement of kidney cysts, ultimately leading to kidney failure.Common extra-renal manifestations include polycystic liver disease, cerebral aneurysms, and cardiac valve abnormalities.The primary genetic causes are mutations in the PKD1 and PKD2 genes. Currently,Tolvaptan, a vasopressin-2 receptor antagonist, is the only approved therapy,which primarily slows kidney function decline without addressing extra-renal complications. Research indicates that cyst-lining epithelial cells in ADPKD are glucose-dependent due to metabolic alterations, including defective glucose metabolism, impaired beta-oxidation, and abnormal mitochondrial activity(Warburg effect).Thus, dietary manipulation to induce ketosis and deprive these cells of glucose is a promising therapeutic strategy.

Methods

The Grease II study is a phase II, 24-month randomized, parallel-group, two-arm superiority trial with a 1:1 allocation. It aims to evaluate the efficacy of a ketogenic diet (Modified Atkins Diet - MAD) compared to a balanced normocaloric diet (BND) in 92 patients with rapidly progressive ADPKD. During the run-in period blood pressure and lipid abnormalities will be normalized, if necessary. The primary outcome is the difference in kidney volume enlargement between the two groups, assessed by MRI at baseline and after 12 months. To mitigate potential biases from glycogen depletion induced by the ketogenic diet, MRIs will be performed after a 30-day switch to the BND diet for both groups. Secondary outcomes include, renal function comparison between the two groups, calculated using the CKD-EPI formula on creatinine and cystatin, at the end of the study(24 months of follow up).

Results

We anticipate achieving three primary endpoints: confirmation of MAD’s tolerability through questionnaire data, confirmation of safety monitored via laboratory tests and clinical observations, reduction in Total Kidney Volume, measured by MRI, in the MAD group. Secondary endpoints include improvements in renal function and the impact of MAD on exploratory biomarkers.

Conclusion

The study is on going and 23 patients were recruited. This study was funded by the Italian ministry of Health - RF-2021- 12374522

Funding

• Government Support – Non-U.S.