New therapies: calcimimetics, phosphate binders and vitamin D receptor activators.
At present, new compounds are available to treat secondary hyperparathyroidism, namely calcimimetics, novel phosphorus binders and also novel vitamin D receptor activators. Calcimimetics increase the sensitivity of the parathyroid gland to calcium through spatial configurational changes of the calcium-sensing receptor. In addition, experimental studies have demonstrated that calcimimetics also upregulate both the calcium-sensing receptor and the vitamin D receptor. They are efficacious in children, though the experience in paediatric chronic kidney disease is still limited. Sevelamer, lanthanum carbonate and magnesium iron hydroxycarbonate are novel phosphorus binders available on the market. Several studies have demonstrated their efficacy and safety up to 6 years, though costs are the main limitation for a wider use. Since almost all the experience available on the new phosphorus binders comes from its use in adults, studies on children are needed in order to confirm the efficacy and safety of these products. Other new salts and polymers are also being developed. New vitamin D receptor activators, such as paricalcitol, are as effective at suppressing parathyroid hormone (PTH) as the traditional vitamin D receptor activators used for the past two decades, but they have a better and safer profile, showing fewer calcaemic and phosphoraemic effects while preserving the desirable effects of the vitamin D receptor activators on the cardiovascular system, hypertension, inflammation and fibrosis. Their use in children with chronic kidney disease has revealed similar responses to those of adults. The novel compounds discussed in this review should facilitate and improve the management of mineral and bone disorders in children with chronic kidney disease.
Bone and Mineral Research Unit, Instituto Reina Sofia de Investigación, REDinREN ISCIII, Hospital Universitario Central de Asturias, Universidad de Oviedo, Julián Clavería S/N, 33006 Asturias, Spain. cannata@hca.es
Jorge B
JB
Cannata-Andía
Minerva
M
Rodriguez-García
Pablo
P
Román-García
Diego
D
Tuñón-le Poultel
Francisco
F
López-Hernández
Diego
D
Rodríguez-Puyol
D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D002118:Calcium / Q000378:metabolism / Q000627:therapeutic use*; D002614:Chelating Agents / Q000627:therapeutic use; D002648:Child; D000069449:Cinacalcet; D004872:Ergocalciferols / Q000627:therapeutic use; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy*; D007676:Kidney Failure, Chronic / Q000188:drug therapy / Q000378:metabolism; D009281:Naphthalenes / Q000627:therapeutic use; D010280:Parathyroid Glands; D010710:Phosphates / Q000378:metabolism*; D011073:Polyamines / Q000627:therapeutic use; D011485:Protein Binding; D018167:Receptors, Calcitriol / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism; D044169:Receptors, Calcium-Sensing / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism; D000069603:Sevelamer
D050071:Bone Density Conservation Agents; D002614:Chelating Agents; D004872:Ergocalciferols; D009281:Naphthalenes; D010710:Phosphates; D011073:Polyamines; D018167:Receptors, Calcitriol; D044169:Receptors, Calcium-Sensing; C084656:paricalcitol; D000069603:Sevelamer; D002118:Calcium; D000069449:Cinacalcet