Kidney Week

Abstract: PO2433

High Dietary Phosphate Intake Causes Inflammatory Tubular Injury and Fibrosis in Mice

Session Information

• CKD: Inflammation, Endothelial Dysfunction, and Signaling
  November 04, 2021 | Location: On-Demand, Virtual Only
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2103 CKD (Non-Dialysis): Mechanisms

Authors

• Vogt, Isabel, Hannover Medical School Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover, Germany

Isabel Vogt

• Richter, Beatrice, Hannover Medical School Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover, Germany

Beatrice Richter,

• Walter, Stefanie, Hannover Medical School Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover, Germany

Stefanie Walter,

• Schmitz, Jessica, Hannover Medical School Institute of Pathology, Nephropathology Unit, Hannover, Germany

Jessica Schmitz,

• Braesen, Jan H., Hannover Medical School Institute of Pathology, Nephropathology Unit, Hannover, Germany

Jan H. Braesen,

• Schmitt, Roland, Hannover Medical School Department of Nephrology and Hypertension, Hannover, Germany

Roland Schmitt,

• Haffner, Dieter, Hannover Medical School Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover, Germany

Dieter Haffner,

• Leifheit-Nestler, Maren, Hannover Medical School Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover, Germany

Maren Leifheit-Nestler,

Background

Due to the increasing consumption of processed food, the dietary inorganic phosphate intake clearly exceeds the recommended daily allowance. Elevated phosphate levels are associated with a higher cardiovascular and all-cause mortality in the general population and accelerated progression of chronic kidney disease (CKD). It is under investigation whether chronic phosphate load represents a renal health risk in the absence of CKD.

Methods

Male C57BL/6 mice were fed with a 2% high phosphate diet (HPD) or respective 0.8 % normal phosphate diet (NPD) for six months. We collected blood, urine and kidneys to investigate phosphate metabolism, kidney function, tissue alterations and inflammation.

Results

Six months HPD significantly increased plasma levels of the phosphaturic hormone fibroblast growth factor (FGF) 23 resulting in enhanced phosphaturia and elevated serum phosphate level. HPD in mice caused albuminuria and increased plasma creatinine level. Histological analyses revealed that mice on HPD develop proximal tubular injury characterized by loss of cell polarity and brush border membranes, flattened epithelia, increased proliferation, mononuclear interstitial infiltration and fibrosis. The kidney damage in HPD was accompanied by increased renal expression of the kidney injury marker Kim-1 und Ngal mice. Kim-1 accumulated in regions of tubular lesions. Flow cytometry analysis demonstrated that the HPD reduced storage of Ly6C^hi monocytes in the spleen and concurrently, enhanced accumulation of F4/80⁺ macrophages and dendritic cells in the kidney. Histological analyses proofed accumulation of F4/80⁺ macrophages and CD3⁺ T-cells in areas of tubular injury that associated with increased renal expression of chemotaxis and growth factors for monocytes and macrophages Ccl2, Csf1 and Il34 in HPD mice. Finally, HPD caused renal fibrosis associated with increased collagen 1, Ctgf, and Tgfb1 expression.

Conclusion

Chronic high phosphate load impairs kidney function by causing a strong inflammatory response and proximal tubular injury in healthy mice. Our results indicate that chronic high phosphate intake might be a renal health risk not only for CKD patients but also for the general population.