Circulating form of Klotho protein — a novel inhibitor of vascular calcification in chronic kidney disease

Ю. С. Милованов¹, Л. Ю. Милованова¹, М. М. Саблина², М. М. Маркина¹, Д. В. Крюкова²

Authors: Yu. S. Milovanov1, L.Yu. Milovanova1, M. M. Sablina2, M. M. Markina1, D. V. Kryukova2

Place: Moscow, Russia

Institution: 1 First Moscow State Medical University named after I. M. Sechenov
2 Lomonosov Moscow State University

Abstract: Objective. To study associations between serum soluble Klotho level and vascular calcification in patients with chronic kidney disease (CKD) 1-5 stages. Design and methods. We examined 70 patients with different stages of CKD, including 41 patients with chronic glomerulonephritis, among them 10 with systemic diseases, 22 with tubulo-interstitial nephritis (bacterial, gout and drug-induced) and 7 with hypertensive nephrosclerosis. All 70 patients with 1-5 stages of CRD underwent clinical examination and blood tests for serum Klotho levels by enzyme-linked immunosorbent assay. Vascular stiffness was assessed in 57 patients by applanation tonometry method (SphygmoCor, AtCor Medical, Australia). Results. Serum Klotho levels differed depending on the stage of CKD. When patients with different stages of CKD were compared, a reverse correlation between serum Klotho level and serum phosphorus level and intact parathormone was found in CKD progression. There is a correlation between serum Klotho level and an increase in left ventricular posterior wall thickness in patients with CKD and hypertension (n = 49). Also reduction in serum Klotho level is associated with a greater frequency of calcifications in heart and major arteries, increased vascular stiffness and reduced blood flow in the tibial arteries (ankle-brachial index). Conclusions. Thus, circulating Klotho plays an important role in mineral metabolism in CKD and demonstrates pleiotropic effects that might modify cardiovascular risk through the impact on vascular calcification and cardiovascular remodeling.  

Keywords: chronic kidney disease, hypertension, circulating Klotho protein, ectopic calcification, cardiovascular remodeling

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