title: [Pathologies of calcium-phosphate homeostasis].
abstract: 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.
authors: Zakład Biochemii i Medycyny Doświadczalnej, Instytut, "Pomnik--Centrum Zdrowia Dziecka", Al. Dzieci Polskich 20, 04-730 Warszawa. biochemia@czd.pl
authors: Elzbieta
authors: E
authors: Karczmarewicz
authors: Edyta
authors: E
authors: Czekuć-Kryskiewicz
authors: Roman S
authors: RS
authors: Lorenc
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D001842:Bone and Bones / Q000378:metabolism; D002117:Calcitriol / Q000378:metabolism; D002130:Calcium Phosphates / Q000378:metabolism*; D018450:Disease Progression; D000089703:Fibroblast Growth Factor-23; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D054559:Hyperphosphatemia / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D010280:Parathyroid Glands / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use; D015854:Up-Regulation; D014807:Vitamin D / Q000378:metabolism
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D002130:Calcium Phosphates; C000717427:FGF23 protein, human; D010281:Parathyroid Hormone; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D014807:Vitamin D; D000089703:Fibroblast Growth Factor-23; D002117:Calcitriol