[Pathologies of calcium-phosphate homeostasis]

The colossal progress in understanding of vitamin D and phosphate metabolism introduces new perspectives in chronic kidney disease (CKD) therapy. Increasing demand for phosphate excretion per nephron triggers the vicious cycle that leads to increase in FGF-23 and PTH and decrease in vitamin D and Klotho. Restriction of dietary phosphate intake (low phosphate diet) and administration of phosphate binder can be regarded as the most important interventions in this case. Because the vicious cycle is likely activated long before hyperphosphatemia occurs during CKD progression, phosphate restriction would have been more effective if started before serum phosphate levels increased, perhaps as soon as serum FGF-23 levels rose. Phosphate restriction alleviates phosphate overload per nephron and can disrupt the vicious cycle: phosphate restriction can reduce serum FGF-23 levels and increase vitamin D, which in turn increase Klotho expression in kidney and parathyroid glands. Inhibitors of rennin-angiotensin system (rosiglitazone, angiotensin-converting enzyme inhibitors) and proper vitamin D supplementation may also up-regulate Klotho expression. Increased Klotho in the kidney may improve FGF-23 sensitivity, which further reduce the amount of FGF-23 required for excreting a given amount of phosphate. Increased Klotho in parathyroid may improve the ability of FGF-23 to suppress PTH. Proper supplementation with vitamin D increase the concentration of substrate for local 1,25(OH)2D synthesis 25(OH)D, which directly suppress PTH, increase Klotho, and decrease FGF-23 by proanabolic action on bone. Improving vitamin D status by inhibition of CYP24A is also under evaluation, as well as antibodies against FGF-23, as modern therapies in CKD.