Figure 9

Summary figure. In vitamin D₃-treated Npt2a^−/− mice, a circulus vitiosus is observed leading to kidney failure. We hypothesize that vitamin D₃ treatment leads to elevated plasma Ca²⁺ levels (possibly via increased bone resorption as indicated by greater CTX-1 levels and/or increased intestinal Ca²⁺ absorption) and decreased intestinal P_i absorption (via lower Npt2b and claudin-3 levels). A combination of vitamin D₃, elevated plasma P_i, and reduced kidney function causes FGF23 levels to be drastically elevated, subsequently diminishing Npt2c abundance and leading to supersaturation of tubular fluid with Ca²⁺ and P_i. Formation of Ca²⁺/P_i crystals lead to renal calcification and reduced kidney function (increase in plasma creatinine and urinary albumin). Consequently, plasma Ca²⁺ and P_i levels are further increased. Green arrows indicate an increase, red arrows indicate a decrease. The table on the right summarizes the most significant findings observed between vitamin D₃ treated mice and vehicle treated mice for both genotypes.