Supplementary Material for: The Role of Extracellular Phosphate Levels on Kidney Disease Progression in a Podocyte Injury Mouse Model Maeda A. Fukushima N. Horiba N. Segawa H. Miyamoto K. 10.6084/m9.figshare.7687775.v1 https://karger.figshare.com/articles/dataset/Supplementary_Material_for_The_Role_of_Extracellular_Phosphate_Levels_on_Kidney_Disease_Progression_in_a_Podocyte_Injury_Mouse_Model/7687775 <b><i>Background:</i></b> Hyperphosphatemia is a major accelerator of complications in chronic kidney disease and dialysis, and phosphate (Pi) binders have been shown to regulate extracellular Pi levels. Research on hyperphosphatemia in mouse models is scarce, and few models display hyperphosphatemia induced by glomerular injury, despite its relevance to human glomerular disease conditions. In this study, we investigated the involvement of hyperphosphatemia in kidney disease progression using a mouse model in which hyperphosphatemia is induced by focal segmental glomerulosclerosis (FSGS). <b><i>Methods:</i></b> We established the NEP25 mouse model in which FSGS-hyperphosphatemia is induced by podocyte injury and evaluated the effect of a Pi binder, sevelamer. <b><i>Results:</i></b> After disease induction, we confirmed a gradual increase in serum Pi accompanied by reduced renal function and observed increases in serum FGF23 and PTH. Treatment with sevelamer significantly reduced serum Pi and urinary Pi fractional excretion and suppressed increases in serum FGF23 and PTH. A high dose improved serum creatinine and tubular injury markers, and pathological analysis confirmed amelioration of glomerular and tubular damage. Gene expression and marker analysis suggested protective effects on tubular epithelial cells in the diseased kidney. Compared to disease control, NEP25 mice treated with sevelamer retained their mRNA expression of Klotho, a known FGF23 co-receptor and renoprotective factor. <b><i>Conclusions:</i></b> Hyperphosphatemia caused by renal function decline was observed in a FSGS-induced NEP25 mouse model. Studies using this model showed that Pi regulation had a positive impact on kidney disease progression, and notably on tubular epithelial cell injury, which indicates the importance of Pi regulation in the treatment of kidney disease progression. 2019-02-07 13:15:35 Focal segmental glomerulosclerosis Kidney disease Phosphate Phosphate binder Renal function