Renoprotective effects of sucroferric oxyhydroxide in a rat model of chronic renal failure

Nephrol Dial Transplant. 2020 Oct 1;35(10):1689-1699. doi: 10.1093/ndt/gfaa080.

Abstract

Introduction: Sucroferric oxyhydroxide (PA21) is an efficacious, well-tolerated iron-based phosphate binder and a promising alternative to existing compounds. We compared the effects of PA21 with those of a conventional phosphate binder on renal function, mineral homeostasis and vascular calcification in a chronic kidney disease-mineral and bone disorder (CKD-MBD) rat model.

Methods: To induce stable renal failure, rats were administered a 0.25% adenine diet for 8 weeks. Concomitantly, rats were treated with vehicle, 2.5 g/kg/day PA21, 5.0 g/kg/day PA21 or 3.0 g/kg/day calcium carbonate (CaCO3). Renal function and calcium/phosphorus/iron metabolism were evaluated during the study course. Renal fibrosis, inflammation, vascular calcifications and bone histomorphometry were quantified.

Results: Rats treated with 2.5 or 5.0 g/kg/day PA21 showed significantly lower serum creatinine and phosphorus and higher ionized calcium levels after 8 weeks of treatment compared with vehicle-treated rats. The better preserved renal function with PA21 went along with less severe anaemia, which was not observed with CaCO3. Both PA21 doses, in contrast to CaCO3, prevented a dramatic increase in fibroblast growth factor (FGF)-23 and significantly reduced the vascular calcium content while both compounds ameliorated CKD-related hyperparathyroid bone.

Conclusions: PA21 treatment prevented an increase in serum FGF-23 and had, aside from its phosphate-lowering capacity, a beneficial impact on renal function decline (as assessed by the renal creatinine clearance) and related disorders. The protective effect of this iron-based phosphate binder on the kidney in rats, together with its low pill burden in humans, led us to investigate its use in patients with impaired renal function not yet on dialysis.

Keywords: FGF-23; chronic kidney disease; iron; phosphate binding; vascular calcification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Drug Combinations
  • Ferric Compounds / therapeutic use*
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors / blood
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / drug therapy*
  • Male
  • Phosphorus / blood
  • Rats
  • Rats, Wistar
  • Sucrose / therapeutic use*
  • Vascular Calcification / etiology
  • Vascular Calcification / prevention & control*

Substances

  • Drug Combinations
  • FGF23 protein, human
  • Ferric Compounds
  • sucroferric oxyhydroxide
  • Phosphorus
  • Sucrose
  • Fibroblast Growth Factors
  • Fibroblast Growth Factor-23