1. ¹Service de Néphrologie et Dialyse, Clinique de l'Orangerie, Aubervilliers, France
2. ²Service de Physiologie-Explorations Fonctionnelles, Hôpital Necker, Paris, France
3. ³INSERM Unit 811, Hôpital Necker-Enfants Malades, Paris, France
4. ⁴INSERM Unit 773, Faculté de Médecine Xavier Bichat, Paris, France

Correspondence: P-Ureña Torres, Service de Néphrologie et Dialyse, Clinique de l'Orangerie, 11 Boulevard Anatole France, Aubervilliers 93300, France. E-mail: urena.pablo@wanadoo.fr

Received 14 November 2006; Revised 26 December 2006; Accepted 2 January 2007; Published online 28 February 2007.

Abstract

Klotho gene mutation leads to a syndrome strangely resembling chronic kidney disease patients undergoing dialysis with multiple accelerated age-related disorders, including hypoactivity, sterility, skin thinning, muscle atrophy, osteoporosis, vascular calcifications, soft-tissue calcifications, defective hearing, thymus atrophy, pulmonary emphysema, ataxia, and abnormalities of the pituitary gland, as well as hypoglycemia, hyperphosphatemia, and paradoxically high-plasma calcitriol levels. Conversely, mice overexpressing klotho show an extended existence and a slow aging process through a mechanism that may involve the induction of a state of insulin and oxidant stress resistance. Two molecules are produced by the klotho gene, a membrane bound form and a circulating form. However, their precise biological roles and molecular functions have been only partly deciphered. Klotho can act as a circulating factor or hormone, which binds to a not yet identified high-affinity receptor and inhibits the intracellular insulin/insulin-like growth factor-1 (IGF-1) signaling cascade; klotho can function as a novel -glucuronidase, which deglycosylates steroid -glucuronides and the calcium channel transient receptor potential vallinoid-5 (TRPV5); as a cofactor essential for the stimulation of fibroblast growth factor (FGF) receptor by FGF23. The two last functions have propelled klotho to the group of key factors regulating mineral and vitamin D metabolism, and have also stimulated the interest of the nephrology community. The purpose of this review is to provide a nephrology-oriented overview of klotho and its potential implications in normal and altered renal function states.