Effect of vitamin D receptor activators on serum Klotho levels in 3b–4 stages chronic кidney disease patients: a prospective randomized study

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Abstract

Background. High risk of cardiovascular events is among leading problems in chronic kidney disease (CKD). Serum Klotho is supposed to be cardio- and nephroprotective; modification of its levels may be important in CKD.

Aim. To evaluate the impact of vitamin D receptor activators (VDRA) on Klotho serum levels in CKD 3b–4 stages patients.

Materials and methods. Study included 90 CKD 3b–4 stages patients who had elevated serum levels of parathyroid hormone (PTH). From them, 47 patients (group 1) started to treat with the selective VDRA (zemplar 1 mcg/day), and 43 patients (group 2) started to treat with non-selective VDRA (alfacalcidol 0.25 mcg/day). At baseline and after 12 months we conducted routine examination, serum Klotho measurement, and broad cardiovascular examination.

Results. The patients who managed to maintain a target serum PTH level, had higher Klotho serum level (p=0.037) at the end of the study. Patients who used selective VDRA significantly more often reached the target PTH level (p=0.032), had higher serum Klotho levels (p=0.037), and glomerular filtration rate (eGFR) level (p=0.048) than patients who used non-selective VDRA. In addition, patients treated with alfacalcidol more than 6 months, more often had hypercalcemia (p=0.047) and hyperphosphatemia (p=0.035). Group 2 showed higher: pulse wave velocity (p=0.051), left ventricular myocardial mass index (p=0.033), and more advanced heart valve calcification (p=0.038).

Conclusion. Successful parathyroid hormone level control with vitamin D receptor activators was associated with higher serum Klotho, selective agents having shown greater effect. Long-term treatment with selective vitamin D receptor activators may contribute to cardiovascular calcification prevention by modifying Klotho levels.

About the authors

Ludmila Yu. Milovanova

Sechenov First Moscow State Medical University (Sechenov University)

Author for correspondence.
Email: Ludm.milovanova@gmail.com
ORCID iD: 0000-0002-5599-0350

д-р мед. наук, проф. каф. внутренних, профессиональных болезней и ревматологии ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» (Сеченовский Университет)

Russian Federation, Moscow

Vladimir D. Beketov

Sechenov First Moscow State Medical University (Sechenov University)

Email: Ludm.milovanova@gmail.com
ORCID iD: 0000-0002-6377-0630

канд. мед. наук, доц. каф. внутренних, профессиональных болезней и ревматологии ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» (Сеченовский Университет)

Russian Federation, Moscow

Svetlana Yu. Milovanova

Sechenov First Moscow State Medical University (Sechenov University)

Email: Ludm.milovanova@gmail.com
ORCID iD: 0000-0002-2687-6161

д-р мед. наук, проф. каф. внутренних, профессиональных болезней и ревматологии ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» (Сеченовский Университет)

Russian Federation, Moscow

Marina V. Taranova

Sechenov First Moscow State Medical University (Sechenov University)

Email: Ludm.milovanova@gmail.com
ORCID iD: 0000-0002-7363-6195

канд. мед. наук, доц. каф. внутренних, профессиональных болезней и ревматологии ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» (Сеченовский Университет)

Russian Federation, Moscow

Vasilii V. Kozlov

Sechenov First Moscow State Medical University (Sechenov University)

Email: Ludm.milovanova@gmail.com
ORCID iD: 0000-0002-2389-3820

доц. каф. общественного здоровья и организации здравоохранения ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» (Сеченовский Университет)

Russian Federation, Moscow

Anastasiia I. Pasechnik

Lomonosov Moscow State University

Email: Ludm.milovanova@gmail.com
ORCID iD: 0000-0002-7544-3696

ординатор каф. внутренних болезней фак-та фундаментальной медицины ФГБОУ ВО «МГУ им. М.В. Ломоносова»

Russian Federation, Moscow

Vladimir A. Reshetnikov

Sechenov First Moscow State Medical University (Sechenov University)

Email: Ludm.milovanova@gmail.com
ORCID iD: 0000-0002-2987-7995

д-р мед. наук, проф. каф. общественного здоровья и организации здравоохранения ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» (Сеченовский Университет)

Russian Federation, Moscow

Tatiana V. Androsova

Sechenov First Moscow State Medical University (Sechenov University)

Email: Ludm.milovanova@gmail.com
ORCID iD: 0000-0002-9951-126X

канд. мед. наук, доц. каф. внутренних, профессиональных болезней и ревматологии ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» (Сеченовский Университет)

Russian Federation, Moscow

Mikhail V. Kalashnikov

Sechenov First Moscow State Medical University (Sechenov University)

Email: Ludm.milovanova@gmail.com
ORCID iD: 0000-0003-4828-6338

аспирант каф. внутренних, профессиональных болезней и ревматологии ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» (Сеченовский Университет)

Russian Federation, Moscow

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2. Fig. 1. Dynamics of mean serum levels of Кlotho and PTH in patients with CKD on the vitamin D receptor activator therapy during the observation period (Mann–Whitney U-test). Group 1 patients had statistically significantly lower PTH levels (p=0.032) and higher Klotho levels (p=0.037) at the end of the study compared with group 2.

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