Phosphate and Klotho.

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Klotho is a putative aging suppressor gene encoding a single-pass transmembrane co-receptor that makes the fibroblast growth factor (FGF) receptor specific for FGF-23. In addition to multiple endocrine organs, Klotho is expressed in kidney distal convoluted tubules and parathyroid cells, mediating the role of FGF-23 in bone-kidney-parathyroid control of phosphate and calcium. Klotho&x207B;/&x207B; mice display premature aging and chronic kidney disease-associated mineral and bone disorder (CKD-MBD)-like phenotypes mediated by hyperphosphatemia and remediated by phosphate-lowering interventions (diets low in phosphate or vitamin D; knockouts of 1α-hydroxylase, vitamin D receptor, or NaPi cotransporter). CKD can be seen as a state of hyperphosphatemia-induced accelerated aging associated with Klotho deficiency. Humans with CKD experience decreased Klotho expression as early as stage 1 CKD; Klotho continues to decline as CKD progresses, causing FGF-23 resistance and provoking large FGF-23 and parathyroid hormone increases, and hypovitaminosis D. Secreted Klotho protein, formed by extracellular clipping, exerts FGF-23-independent phosphaturic and calcium-conserving effects through its paracrine action on the proximal and distal tubules, respectively. We contend that decreased Klotho expression is the earliest biomarker of CKD and the initiator of CKD-MBD pathophysiology. Maintaining normal phosphate levels with phosphate binders in patients with CKD with declining Klotho expression is expected to reduce mineral and vascular derangements.

Original languageEnglish (US)
JournalKidney international. Supplement
Issue number121
StatePublished - Apr 2011

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Phosphates
Chronic Kidney Disease-Mineral and Bone Disorder
Hyperphosphatemia
Distal Kidney Tubule
Suppressor Genes
Premature Aging
Fibroblast Growth Factor Receptors
Calcitriol Receptors
Mixed Function Oxygenases
Parathyroid Hormone
Vitamin D
Minerals
Blood Vessels
Biomarkers
fibroblast growth factor 23
Diet
Calcium
Phenotype
Kidney
Bone and Bones

ASJC Scopus subject areas

  • Nephrology

Cite this

Phosphate and Klotho. / Kuro-O, Makoto.

In: Kidney international. Supplement, No. 121, 04.2011.

Research output: Contribution to journalArticle

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