FGF23-parathyroid interaction: implications in chronic kidney disease

被引：119

作者：

Komaba, Hirotaka ^{[2
,3
]}

Fukagawa, Masafumi ^{[1
,2
,3
]}

机构：

[1] Tokai Univ, Sch Med, Div Nephrol & Metab, Isehara, Kanagawa 2591193, Japan

[2] Kobe Univ, Sch Med, Div Nephrol, Kobe, Hyogo 650, Japan

[3] Kobe Univ, Sch Med, Kidney Ctr, Kobe, Hyogo 650, Japan

来源：

KIDNEY INTERNATIONAL | 2010年 / 77卷 / 04期

关键词：

chronic kidney disease; FGF23; Klotho; parathyroid hormone; vitamin D; FIBROBLAST GROWTH FACTOR-23; FAMILIAL TUMORAL CALCINOSIS; VITAMIN-D METABOLISM; SECONDARY HYPERPARATHYROIDISM; PARATHYROID-HORMONE; DIALYSIS PATIENTS; TRANSGENIC MICE; CIRCULATING FIBROBLAST-GROWTH-FACTOR-23; POSTTRANSPLANT HYPOPHOSPHATEMIA; RENAL-TRANSPLANTATION;

D O I：

10.1038/ki.2009.466

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

Over the past few years there have been considerable advances in our understanding of the physiological regulation of mineral homeostasis. One of the most important breakthroughs is the identification of fibroblastic growth factor 23 (FGF23) and its role as a key regulator of phosphate and 1,25-dihydroxyvitamin D metabolism. FGF23 exerts its biological functions by binding to its cognate receptor in the presence of Klotho as a cofactor. FGF23 principally acts on the kidney to induce urinary phosphate excretion and suppresses 1,25-dihydroxyvitamin D synthesis, thereby indirectly modulating parathyroid hormone secretion. FGF23 also acts directly on the parathyroid to decrease parathyroid hormone synthesis and secretion. In patients with chronic kidney disease, FGF23 levels increase progressively to compensate for phosphate retention, but these elevated FGF23 levels fail to suppress the secretion of parathyroid hormone, particularly in the setting of uremia. Recent data suggest that this parathyroid resistance to FGF23 may be caused by decreased expression of Klotho-FGFR1 complex in hyperplastic parathyroid glands. This review summarizes recent insights into the role of FGF23 in mineral homeostasis and discusses the involvement of its direct and indirect interaction with the parathyroid gland, particularly focusing on the pathophysiology of secondary hyperparathyroidism in chronic kidney disease. Kidney International (2010) 77, 292-298; doi: 10.1038/ki.2009.466; published online 9 December 2009

引用

页码：292 / 298

页数：7

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