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Abstract: PO2035

Efficacy of Pi-Binder Lanthanum Carbonate in Reversing Systemic Effects of a High-Phosphate Diet in Mice

Session Information

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

  • 1800 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

  • Alappan, Uma Devi, Emory University, Atlanta, Georgia, United States
  • Viggeswarapu, Manjula, VA Medical Center Atlanta, Decatur, Georgia, United States
  • Arnst, Jamie, Emory University, Atlanta, Georgia, United States
  • Beck, George R., Emory University, Atlanta, Georgia, United States
Background

Modulating dietary inorganic phosphorus (Pi) is particularly important for patients suffering from chronic kidney disease (CKD) as excess Pi consumption and subsequent elevated serum Pi levels can lead to significant health problems, including increased mortality. Recent data now suggests that high Pi consumption might also have negative health consequences even in those with clinically normal renal function. The predominant clinical therapy to reduce serum Pi and related health complications of CKD patients is orally administered Pi-binders with meals, including the commonly used Lanthanum Carbonate (LaC). Our study assessed the strategy of binding Pi in the gut to reduce health consequences of a high Pi diet including changes in bone volume, Pi-responsive circulating factors, and gene expression in the kidney.

Methods

Healthy 10-Week-old, female C57BL/6J mice were fed diets with varying Pi for 5 weeks: Low Pi (LPD, 0.2% Pi), Normal Pi (NPD, 0.6% Pi), High Pi (HPD, 1.8% Pi), and HPD supplemented with LaC (3%). All diets contained 0.6% Calcium, similar protein, Kcals, and fat%. Circulating Pi-responsive factors (FGF23, OPN) were measured by ELISA, bone volume by micro-computed tomography, and gene expression in the kidney by quantitative real-time (qRT) PCR.

Results

HPD resulted in increased serum FGF23 and OPN, decreased bone volume (trabecular, cortical), and significant changes in kidney gene expression of inflammatory protein Lcn2, Pi responsive Klotho, vitamin D synthesis Cyp27b1, and Pi-transporter Slc34a2. LaC completely reversed the HPD-induced increase in serum FGF23, partially reversed gene expression changes in the kidney but did not alter HPD-induced bone loss.

Conclusion

The clinically used Pi-binder LaC only reversed certain HPD-induced consequences, suggesting a multifactorial mechanism, and therefore may require a therapeutic strategy beyond reducing gut Pi-absorption. Decreasing Pi consumption was substantially more effective at minimizing physiological repercussions like bone loss. Changes in kidney gene expression after a sustained HPD also reveal potential long-term consequences on kidney health/function in otherwise healthy individuals. Given divergent claims concerning LaC binder efficacy, our study shows LaC corrects some—but not all—effects of a high Pi diet.

Funding

  • Veterans Affairs Support