Kidney Week

Abstract: TH-OR07

Renoprotective Effects of Ferric Citrate in a Mouse Model of CKD

Session Information

• Breakthroughs in Anemia and Iron Management
  October 22, 2020 | Location: Simulive
  Abstract Time: 05:00 PM - 07:00 PM

Category: Anemia and Iron Metabolism

• 200 Anemia and Iron Metabolism

Authors

• Hanudel, Mark R., University of California Los Angeles David Geffen School of Medicine, Los Angeles, California, United States

Mark R. Hanudel, MD, MS, FASN



I am an Assistant Professor of Pediatrics at UCLA, in the Division of Nephrology. I completed my undergraduate studies at Yale University, medical degree at Harvard Medical School, pediatric residency at UCLA, and pediatric nephrology fellowship at UCLA. My research focuses on studying the interrelated complications of chronic kidney disease, including iron dysregulation, anemia, disordered bone and mineral metabolism, and heart disease. My mentors are Drs. Isidro Salusky, Tomas Ganz, and Elizabeta Nemeth. I am currently supported by an American Society of Nephrology Carl W. Gottschalk Research Scholar Grant.

• Wong, Shirley, University of California Los Angeles David Geffen School of Medicine, Los Angeles, California, United States

Shirley Wong,

• Chua, Kristine, University of California Los Angeles David Geffen School of Medicine, Los Angeles, California, United States

Kristine Chua,

• Jung, Grace, University of California Los Angeles David Geffen School of Medicine, Los Angeles, California, United States

Grace Jung,

• Qiao, Bo, University of California Los Angeles David Geffen School of Medicine, Los Angeles, California, United States

Bo Qiao,

• Gabayan, Victoria Rivka, University of California Los Angeles David Geffen School of Medicine, Los Angeles, California, United States

Victoria Rivka Gabayan,

• Ganz, Tomas, University of California Los Angeles David Geffen School of Medicine, Los Angeles, California, United States

Tomas Ganz,

Background

Ferric citrate (FC) is an effective phosphate binder and iron replacement product. In the setting of chronic kidney disease (CKD), both decreasing enteral phosphate absorption and improving iron status could lower pathologically elevated FGF23 levels and indirectly improve kidney function. In a murine model of CKD, we assessed how FC (and iron status in general) affects FGF23 levels and kidney function.

Methods

Five-week-old Col4α3 knockout mice were placed on five-week diets containing low iron (4 ppm), standard iron (48 ppm), or standard iron supplemented with FC (48 ppm + 1% FC) (n = 15-20 mice per group). Mice were euthanized at ten weeks of age.

Results

Compared to the standard iron diet group, the mice on low iron diets developed iron deficiency anemia (lower liver iron, lower hemoglobin, lower mean corpuscular volume, and higher red cell distribution width); markedly worsened kidney function (higher serum urea nitrogen, creatinine, and phosphate); and markedly higher FGF23 levels (increased bone and marrow Fgf23 mRNA expression, and approximately ten-fold higher plasma intact FGF23 concentrations) (Figure). Conversely, compared to the standard iron diet group, the mice treated with FC had similar hemoglobin (with increases in liver and serum iron not reaching statistical significance), but decreased serum phosphate; decreased marrow Fgf23 mRNA expression; approximately ten-fold lower plasma intact FGF23 concentrations; decreased systemic inflammation; and markedly improved kidney function (decreased serum urea nitrogen, serum creatinine, urine albumin-to-creatinine ratio, and expression of renal fibrosis markers, along with increased kidney Klotho mRNA expression) (Figure).

Conclusion

In the setting of CKD, iron deficiency anemia is associated with markedly increased intact FGF23 levels and worsened kidney function. In this CKD model, compared to either iron-deficient or standard iron conditions, FC decreased serum phosphate, markedly decreased intact FGF23, and dramatically improved kidney function. These data support further human studies of how FC affects CKD progression.

Funding

• Commercial Support –