Clinical and Experimental Nephrology

, Volume 22, Issue 6, pp 1351–1359 | Cite as

Effect of essential amino acid кetoanalogues and protein restriction diet on morphogenetic proteins (FGF-23 and Кlotho) in 3b–4 stages chronic кidney disease patients: a randomized pilot study

  • Lyudmila Milovanova
  • Victor Fomin
  • Sergey Moiseev
  • Marina Taranova
  • Yury Milovanov
  • Lidia Lysenko (Kozlovskaya)
  • Vasiliy Kozlov
  • Elena Kozevnikova
  • Svetlana Milovanova
  • Marina Lebedeva
  • Vladimir Reshetnikov
Original Article



A low protein diet (LPD) with essential amino acid ketoanalogue supplementation (KA) may contribute in improving of chronic kidney disease (CKD), while the exact mechanisms of KA’s effect are not established yet. We have conducted a prospective, randomized, controlled comparative study of LPD + KA and LPD alone in relation to serum Klotho, FGF-23 levels in CKD patients.


79 non-diabetic CKD 3b–4 stage patients, compliant with LPD diet (0.6 g/kg of body weight/day), had been selected. The patients were randomized into two groups. The first group (42 patients) received LPD + КA. The second group (37 patients) continued the LРD alone. In addition to routine tests, serum Klotho, FGF-23 levels, as well as bioimpedance analysis, sphygmography (stiffness (augmentation) indices (AI), central (aortal) blood pressure) with a «SphygmaCor» device; echocardiography (valvular calcification score (VCS) and LVMMI), were performed.


There were body mass indices’ decrease (p = 0.046), including muscle body mass in men (p = 0.027) and woman (p = 0.044) in the LPD group to the end of study (14th month). In addition, lower FGF-23 (p = 0.029), and higher sKlotho (p = 0.037) were detected in the LPD + KA group compared to the LPD one. The increase in AI (p = 0.034), VCS (p = 0.048), and LVMMI (p = 0.023) was detected more often in the LPD group at the end of study.


LPD + KA provides support for nutrition status and contributes to more efficient correction of FGF-23 and Klotho abnormalities that may result in cardiovascular calcification and cardiac remodeling decreasing in CKD. At the same time, a prolonged LPD alone may lead to malnutrition.


Chronic kidney disease Essential amino acid ketoanalogues Fibroblast growth factor-23 (FGF-23) Serum alpha-Klotho (sKlotho) Cardiovascular calcification Cardiac remodeling 



This work was supported by the Russian Science Foundation (Grant No. 14-15-00947 2014).

Compliance with ethical standards

Ethical approval

The study was approved by the Institutional Review Board of the Sechenov First Moscow State Medical University (Protocol No. 06–14, 16.06.2014). All the patients provided written informed consent. All the described procedures were performed in accordance with the Helsinki Declaration.

Supplementary material

10157_2018_1591_MOESM1_ESM.doc (58 kb)
Supplementary material 1 (DOC 58 KB)


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Copyright information

© Japanese Society of Nephrology 2018

Authors and Affiliations

  • Lyudmila Milovanova
    • 1
    • 2
  • Victor Fomin
    • 1
    • 3
  • Sergey Moiseev
    • 1
    • 2
  • Marina Taranova
    • 1
    • 2
  • Yury Milovanov
    • 1
    • 2
  • Lidia Lysenko (Kozlovskaya)
    • 1
    • 2
  • Vasiliy Kozlov
    • 1
    • 4
  • Elena Kozevnikova
    • 1
    • 2
  • Svetlana Milovanova
    • 1
    • 2
  • Marina Lebedeva
    • 1
    • 2
  • Vladimir Reshetnikov
    • 1
    • 4
  1. 1.Sechenov First Moscow State Medical University (Sechenov University)MoscowRussian Federation
  2. 2.Clinic of Nephrology and Internal DiseasesMoscowRussian Federation
  3. 3.Department of Faculty Therapy No. 1MoscowRussian Federation
  4. 4.Department of Public Health and Health Care OrganizationMoscowRussian Federation

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