These results forcefully suggested that FGF23-Klotho signaling axis and its downstream ERK1/2-SGK1-NHERF-1-NaPi-2a pathway in the kidney were both dysregulated in the CKD–MBD rat model, and there was a strong causality between unbalanced signaling pathways and phosphorus reabsorption. This evidence concerns the gene MAPK3 and chronic kidney disease.