Creatinine-Normalized Phosphaturia after Phosphate Loading in Skeletal Muscle–Specific Fgf23 Knockout Mice

We read with interest the JASN article by Heitman and colleagues describing phosphate-induced fibroblast growth factor 23 (FGF23) expression in skeletal muscle across CKD and non-CKD models and showing that skeletal muscle–specific FGF23 deletion lowers circulating FGF23 and blunts the urinary phosphate response to acute phosphate loading.1 These observations extend the established role of FGF23 in regulating phosphate homeostasis2 and suggest that skeletal muscle contributes to the endocrine response to hyperphosphatemia. In Figure 5I, urinary phosphate after intraperitoneal phosphate loading is presented as urine phosphate concentration normalized to urine creatinine and body weight.1 Because creatinine excretion is closely tied to muscle mass and turnover, and because skeletal muscle is the genetically targeted tissue in this model, it would be helpful to clarify whether the key inference—reduced phosphaturic response in knockout mice—remains consistent when urinary phosphate handling is summarized using complementary metrics that are less dependent on creatinine normalization. Specifically, were 24-hour urine volumes and total phosphate excretion (e.g., mg/24 h or mmol/24 h) comparable between knockout and control mice after phosphate loading? If paired serum phosphate and creatinine were obtained at the end of the collection, reporting the fractional excretion of phosphate or tubular reabsorption of phosphate would more directly reflect proximal tubular phosphate transport3 and could be derived from the existing serum and urine measurements. Clarifying the magnitude of phosphaturia using these additional, physiology-aligned summaries would further strengthen the interpretation that skeletal muscle–derived FGF23 modulates renal phosphate reabsorption and would facilitate comparisons with previous mechanistic studies of FGF23 signaling in phosphate balance.2,3