Kidney Week

Abstract: TH-PO924

Ketogenic Diet Mitigates Renal Fibrosis and Partially Preserves Kidney Function in Nephrotoxic Serum Nephritis

Session Information

• Health Maintenance, Nutrition, Metabolism - I
  November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Health Maintenance, Nutrition, and Metabolism

• 1500 Health Maintenance, Nutrition, and Metabolism

Authors

• Kloetzer, Konstantin A., Medizinische Universitat Graz, Graz, Steiermark, Austria

Konstantin A. Kloetzer,

• Schuller, Max, Medizinische Universitat Graz, Graz, Steiermark, Austria

Max Schuller,

• Krall, Marcell, Medizinische Universitat Graz, Graz, Steiermark, Austria

Marcell Krall,

• Artinger, Katharina, Medizinische Universitat Graz, Graz, Steiermark, Austria

Katharina Artinger,

• Schabhüttl, Corinna, Medizinische Universitat Graz, Graz, Steiermark, Austria

Corinna Schabhüttl,

• Mooslechner, Agnes Anna, Medizinische Universitat Graz, Graz, Steiermark, Austria

Agnes Anna Mooslechner,

• Habisch, Hansjörg, Medizinische Universitat Graz, Graz, Steiermark, Austria

Hansjörg Habisch,

• Madl, Tobias, Medizinische Universitat Graz, Graz, Steiermark, Austria

Tobias Madl,

• Rosenkranz, Alexander R., Medizinische Universitat Graz, Graz, Steiermark, Austria

Alexander R. Rosenkranz,

• Eller, Philipp, Medizinische Universitat Graz, Graz, Steiermark, Austria

Philipp Eller,

• Eller, Kathrin, Medizinische Universitat Graz, Graz, Steiermark, Austria

Kathrin Eller,

Background

Ketogenic diet (KD) has garnered medical interest due to its potential health benefits in various diseases including a significant regulatory impact on inflammatory processes. Our study examined the effects of a KD on an experimental mouse model of immune-complex-mediated glomerulonephritis (GN).

Methods

Male C57BL/6 mice were put on a KD or continued with standard chow (SC) three days after the induction of nephrotoxic serum nephritis (NTS). Mice were observed for 21 days post-induction. Key parameters like the albumin-to-creatinine ratio (ACR) in spot urine and kidney histology were evaluated. Further, we transitioned mice back to SC on day 21 and observed them for an additional 5 weeks. During this period, kidney function was monitored using transdermal glomerular filtration rate measurement devices. Kidney fibrosis was assessed using Sirius Red staining. To thoroughly examine the molecular mechanisms associated with a ketogenic diet, we employed a multifaceted approach incorporating comprehensive immunophenotyping of blood and lymphatic tissues via flow cytometry and immunohistochemistry, renal NMR spectroscopy (metabolomics), and renal bulk RNA-sequencing.

Results

KD significantly reduced levels of albuminuria. We noticed fewer crescents and lower PAS scores, indicating an improved glomerular phenotype in the KD group, but a trend toward increased tubular injury and tubular fat deposition. Mice switched back to SC after the initial KD phase demonstrated a reduction in kidney fibrosis and preserved kidney function with regression of the tubular fat deposits. KD mice showed major systemic immunological and metabolic adaptions like a reduction in blood leukocyte numbers and an increase in the concentration of renal ketone bodies. We further observed an increase of renal neutrophil infiltrates and changes in bulk inflammatory signatures including a decrease in Mpo expression. Notably, transcriptomics analysis revealed a decrease in extracellular matrix production.

Conclusion

A therapeutic KD was protective in a mouse model of GN, leading to a reduction in albuminuria, preserved kidney function, and reduced renal fibrosis. Further research is needed to fully understand these protective mechanisms.

Funding

• Private Foundation Support