Abstract: TH-PO802
Therapeutic Strategies for Reversing the Negative Health Effects of a High Phosphate Diet in Mice
Session Information
- Health Maintenance, Nutrition, Metabolism
November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Health Maintenance‚ Nutrition‚ and Metabolism
- 1400 Health Maintenance‚ Nutrition‚ and Metabolism
Authors
- Alappan, Uma Devi, Emory University School of Medicine, Atlanta, Georgia, United States
- Arnst, Jamie, Emory University School of Medicine, Atlanta, Georgia, United States
- Viggeswarapu, Manjula, VA Medical Center Atlanta, Decatur, Georgia, United States
- Beck, George R., Emory University School of Medicine, Atlanta, Georgia, United States
Background
Dietary inorganic phosphorus (Pi) regulation is crucial for treating CKD patients as excess serum Pi can lead to comorbidities. Studies show high +Pi may negatively impact those with clinically normal renal function via partly understood mechanisms like increased Pi-responsive factors (PTH, osteopontin [OPN], FGF23), kidney damage, and decreased bone volume. Clinicians commonly administer Lanthanum Carbonate (LaC) Pi-binder to reduce serum Pi, Vitamin D (VitD) to increase bone strength, Cinacalcet (CNC) to suppress PTH, and Zoledronate (Zol) to prevent bone loss. Our study investigates these pharmacologic strategies compared to a low Pi diet to reduce excess Pi’s negative health consequences.
Methods
Healthy 10-Week-old, female C57BL/6J mice were fed diets with Normal Pi (NPD, 0.6% Pi) or High Pi (HPD, 1.8% Pi). All diets contained 0.6% Calcium, 2.2IU VitD, similar protein, Kcals, and fat%. Strategies to control systemic effects of high Pi included: low Pi diet (LPD, 0.2%), HPD + LaC (3%), VitD (10IU) or CNC (100mg/kg) incorporated into the feed, and Zol (100µg/kg ip). Serum FGF23, OPN, PTH were measured by ELISA, bone volume by micro-computed tomography, and kidney gene expression by quantitative real-time (qRT) PCR.
Results
Therapeutic strategies to control Pi-responsive factors were generally as expected with LaC reducing HPD-induced increase in FGF23 and CNC lowering PTH in response to HPD. VitD did not produce an effect and surprisingly Zol somewhat exacerbated response to HPD. Though some strategies controlled systemic, high Pi-related effects, all were generally ineffective at blunting bone loss—except Zol. Changes in kidney-related gene expression—i.e. Klotho, Pi transporters, Lipocalin-2—were influenced by dietary Pi and at least partially corrected with Pi-normalizing strategies. Reducing Pi consumption (LPD) lowered systemic Pi factors and improved bone volume over NPD.
Conclusion
Though individually existing, clinically used therapies are generally effective at correcting some aspects of systemic phosphate dysbiosis in mice, they generally do not correct negative consequences on bone volume. This suggests that the negative health consequences of dysregulated phosphate homeostasis, even in the context of normal renal function, are multifactorial and cannot be fully alleviated with existing clinically used therapies.
Funding
- Veterans Affairs Support