Correction of hyperphosphatemia suppresses cardiac remodeling in uremic rats

Hyperphosphatemia is associated with cardiovascular disease in patients with chronic kidney disease. To examine the effects of correction of hyperphosphatemia, we investigated the association between phosphate metabolism and cardiac remodeling in uremic rats. Four groups were studied for 8 weeks: (1) control (sham), (2) 5/6 nephrectomized (Nx) rats fed a normal phosphate regular diet (Nx + NP), (3) Nx rats fed a high phosphate (1.2 %) diet (Nx + HP), and (4) Nx rats fed a high phosphate diet containing 2 % lanthanum carbonate (Nx + HP + La). The relationship between phosphate metabolism and cardiac remodeling was analyzed. Nx + HP rats showed a significant increase in serum phosphate and PTH compared with Nx + NP rats, while Nx + HP + La rats showed slight decreases in these levels. Both Nx + HP and Nx + HP + La rats showed a significant increase in fibroblast growth factor-23 (FGF23) compared with Nx + NP rats. Urinary phosphate excretion showed a similar trend to that of FGF23. Nx + HP rats showed a significant increase in LV weight and matrix deposition compared with Nx + NP rats, and this increase was also significantly suppressed in Nx + HP + La rats. Serum phosphate levels and PTH were significantly correlated with LV weight and matrix deposition, but FGF23 levels did not show the correlation. FGF23 had a high correlation with urinary phosphate excretion. These results suggest that correction of hyperphosphatemia by lanthanum carbonate could suppress cardiac remodeling independently of changes in FGF23.