Phosphate balance in chronic kidney disease?: the chicken or the egg

• Autor(a) principal: Adragão,Teresa
• Data de Publicação: 2012
• Outros Autores: Frazão,João M.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://scielo.pt/scielo.php?script=sci_arttext&pid=S0872-01692012000200003
• topic: Bone-kidney-parathyroid endocrine axis; chronic kidney disease; FGF23; Klotho; phosphate balance

In chronic kidney disease patients there are three main stimuli for parathyroid hormone (PTH) secretion by the chief cell in the parathyroid glands: hypocalcaemia, low 1,25(OH)2D3 levels and hyperphosphataemia. FGF23 is a regulator of phosphate and vitamin D metabolism. The discovery of FGF23 actions enlightened our understanding of the development of secondary hyperparathyroidism in CKD patients. The main systemic factors that stimulate FGF23 secretion by the osteocyte in the bone appear to be phosphate load and 1,25(OH)2D3. In the kidney, FGF23 decreases the number of Na/Pi co-transporters IIa and IIc in the tubular cell and promotes phosphaturia. FGF23 also reduces 1,25(OH)2D3 levels by inhibiting, in the kidney, its production by 1-alpha-hydroxylase and stimulating its degradation by 24-hydroxylase. Increase in FGF23 levels has been described in early 2 and 3 CKD stages preceding the decrease of 1,25(OH)2D3 levels and hyperphosphatemia. In this sequence of events, increase of FGF23 in CKD patients seems to be a novel mechanism for the early decline of 1,25(OH)2D3 levels observed in these patients. It was hypothesised that klotho deficiency creates a tissue resistance to FGF23 which is responsible for the increase of FGF23 levels. Reduced renal expression of klotho has been demonstrated in CKD patients preceding FGF23 increase. Chronic kidney disease may be considered a state of klotho deficiency with increase of FGF23 levels. Klotho deficiency may be the initial alteration for the development of phosphate retention and secondary hyperparathyroidism in CKD patients. In this article we review the classic and new pathways involved in the development of secondary hyperparathyroidism in chronic kidney disease and the subsequent actions ensuing from this knowledge. It is possible that, in 3 and 4 CKD stages, an early therapeutic intervention consisting of a low phosphate diet and/or phosphate binders, even in the presence of normophosphataemia, might retard the development of secondary hyperparathyroidism