Kidney Week

Abstract: TH-PO941

Sucroferric Oxyhydroxide Ameliorates Glomerular Podocyte and Tubulointerstitial Injury in the Rat Remnant Kidney Model

Session Information

• Molecular Mechanisms of CKD - I
  October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 1903 CKD (Non-Dialysis): Mechanisms

Authors

• Nemoto, Yoshikazu, Teikyo University School of Medicine, Tokyo, ToKyo, Japan

Yoshikazu Nemoto,

• Kumagai, Takanori, Teikyo University School of Medicine, Tokyo, ToKyo, Japan

Takanori Kumagai,

• Shiraishi, Takeshi, Teikyo University School of Medicine, Tokyo, ToKyo, Japan

Takeshi Shiraishi,

• Ishizawa, Kenichi, Teikyo University School of Medicine, Tokyo, ToKyo, Japan

Kenichi Ishizawa,

• Yamazaki, Osamu, Teikyo University School of Medicine, Tokyo, ToKyo, Japan

Osamu Yamazaki,

• Tamura, Yoshifuru, Teikyo University School of Medicine, Tokyo, ToKyo, Japan

Yoshifuru Tamura,

• Kuro-o, Makoto, Jichi Medical University, Shimotsuke, Japan

Makoto Kuro-o,

• Uchida, Shunya, Teikyo University School of Medicine, Tokyo, ToKyo, Japan

Shunya Uchida,

• Shibata, Shigeru, Teikyo University School of Medicine, Tokyo, ToKyo, Japan

Shigeru Shibata,

Background

Previously, we reported that the elevation of serum phosphate can accelerate CKD progression in the retrospective cohort study (Plos One 2016). In this study, we evaluated the protective effects of sucroferric oxyhydroxide (SF), a phosphate binder, in a rat model of CKD.

Methods

SD rats received 5/6 nephrectomy (RK) and had a normal diet containing 0.3% phosphate. Control rats without 5/6 nephrectomy received the same diet. A subgroup of RK rats received SF (50 mg/g chow; RK+SF). Renal histology was evaluated at 8 weeks.

Results

RK rats showed increased FGF23 levels compared with control rats. Serum phosphate levels were also moderately but significantly increased. SF administration significantly decreased serum FGF23 and phosphate levels in RK rats. Urinary phosphate excretion was also significantly lower in RK+SF rats than RK rats. Of note, albuminuria in RK rats was significantly ameliorated by SF administration at 8 weeks (RK, 8.42 ± 1.49 mg/day versus RK+SF, 2.71 ± 1.15 mg/day; P < 0.01). In the PAS-stained kidney sections, SF administration attenuated glomerulosclerosis and tubulointerstitial injury in RK rats. Consistently, gene expression of inflammatory and profibrotic cytokines were significantly lower in the kidney in RK+SF rats than in RK rats. In the glomeruli, we found that the increased expression of desmin, a marker for podocyte injury, was attenuated by SF. Consistently, nephrin protein expression was preserved in RK+SF rats compared with RK rats. The protective effects on podocytes were confirmed by morphological analysis under transmission electron microscope. In von Kossa staining, calcium phosphate was detected neither in RK nor RK+SF rats, indicating that renal injury in this model is independent of ectopic calcification at this stage. Plasma levels of calciprotein particles were significantly lower in RK+SF than RK rats, indicating the reduced mineral stress by SF.

Conclusion

These data indicate that phosphate loading to the kidney causes glomerular and tubulointerstitial injury in the absence of calcium phosphate deposition, and support the pathological role of phosphate loading in CKD progression.