[Role of the morphogenetic proteins FGF-23 and Klotho and the glycoprotein sclerostin in the assessment of the risk of cardiovascular diseases and the prognosis of chronic kidney disease].
AIM. To analyze changes in the serum concentrations of the morphogenetic proteins fibroblast growth factor 23 (FGF-23) and Klotho, as well as sclerostin, an osteocyte-secreted glycoprotein, in relation to the degree of hypertension, left ventricular (LV) hypertrophy, and arterial stiffness in patients with chronic kidney disease (CKD) at its different stages.


METHODS
Sixty-five patients (33 men and 32 women) aged 20-65 years, including 25 with chronic glomerulonephritis, 15 with tubulointerstitial nephritis, and 25 with hypertensive nephrosclerosis, were examined. A control group consisted of 15 healthy volunteers matched to the study group patients for age and gender. Serum FGF-23 concentrations and blood pressure (BP) were measured in the all subjects. Patients with BPs > 140/80 mm Hg underwent echocardiography, followed by determination of LV mass (LVM) and calculation of LVM index. Vascular circulation, pulse wave velocity, cardiac and vascular calcifications, and vascular functional properties were estimated.


RESULTS
There was a strong direct Correlation between the serum concentration of FGF-23 and the stage of CKD and an inverse correlation between the levels of Klotho and sclerostin and the stage of CKD. As the glomerular filtration rate became lower, the concentration of FGF-23 increased and that of Klotho and sclerostin decreased just in Stage III CKD while hyperphosphatemia and elevated parathyroid hormone levels were noted in Stages IV-V CKD. As CKD progressed, the serum concentrations of Klotho and sclerostin were inversely correlated with the levels of phosphorus and parathyroid hormone. The degree of blood pressure elevation correlated positively with serum FGF-23 concentrations and inversely with Klotho levels. There was no significant correlation of the level of sclerostin with the degree of BP increase. The direct correlation between higher FGF-23 level and higher VLM is most pronounced in hypertensive patients. There was a strong direct relationship between FGF-23 and Klotho levels and a strong inverse relationship between sclerostin levels and pulse wave velocity. Lower Klotho concentrations were associated with the detection rate of calcifications in the heart valves and large arteries (the abdominal aorta). The reduced serum levels of Klotho and sclerostin were also correlated with concentric LV remodeling.


CONCLUSIONS
It was demonstrated that there was a clear link between increased serum FGF-23 and decreased Klotho concentration as CKD progressed, and that between arterial stiffness and calcification and myocardial remodelling regardless of traditional risk factors. More experimental and clinical studies are required to clarify the role of sclerostin in CKD.
University Clinical Hospital Three (E.M. Tareev Clinic of Nephrology, Internal and Occupational Diseases), I.M. Sechenov First Moscow Medical University, Ministry of Health of Russia, Moscow, Russia.
L Yu
LY
Milovanova
University Clinical Hospital Three (E.M. Tareev Clinic of Nephrology, Internal and Occupational Diseases), I.M. Sechenov First Moscow Medical University, Ministry of Health of Russia, Moscow, Russia.
Yu S
YS
Milovanov
University Clinical Hospital Three (E.M. Tareev Clinic of Nephrology, Internal and Occupational Diseases), I.M. Sechenov First Moscow Medical University, Ministry of Health of Russia, Moscow, Russia.
D V
DV
Kudryavtseva
University Clinical Hospital Three (E.M. Tareev Clinic of Nephrology, Internal and Occupational Diseases), I.M. Sechenov First Moscow Medical University, Ministry of Health of Russia, Moscow, Russia.
M M
MM
Markina
University Clinical Hospital Three (E.M. Tareev Clinic of Nephrology, Internal and Occupational Diseases), I.M. Sechenov First Moscow Medical University, Ministry of Health of Russia, Moscow, Russia.
S Yu
SY
Milovanova
University Clinical Hospital Three (E.M. Tareev Clinic of Nephrology, Internal and Occupational Diseases), I.M. Sechenov First Moscow Medical University, Ministry of Health of Russia, Moscow, Russia.
L V
LV
Kozlovskaya
University Clinical Hospital Three (E.M. Tareev Clinic of Nephrology, Internal and Occupational Diseases), I.M. Sechenov First Moscow Medical University, Ministry of Health of Russia, Moscow, Russia.
M V
MV
Lebedeva
University Clinical Hospital Three (E.M. Tareev Clinic of Nephrology, Internal and Occupational Diseases), I.M. Sechenov First Moscow Medical University, Ministry of Health of Russia, Moscow, Russia.
V D
VD
Beketov
University Clinical Hospital Three (E.M. Tareev Clinic of Nephrology, Internal and Occupational Diseases), I.M. Sechenov First Moscow Medical University, Ministry of Health of Russia, Moscow, Russia.
S V
SV
Moiseev
University Clinical Hospital Three (E.M. Tareev Clinic of Nephrology, Internal and Occupational Diseases), I.M. Sechenov First Moscow Medical University, Ministry of Health of Russia, Moscow, Russia.
N A
NA
Mukhin
University Clinical Hospital Three (E.M. Tareev Clinic of Nephrology, Internal and Occupational Diseases), I.M. Sechenov First Moscow Medical University, Ministry of Health of Russia, Moscow, Russia.
V V
VV
Fomin
University Clinical Hospital Three (E.M. Tareev Clinic of Nephrology, Internal and Occupational Diseases), I.M. Sechenov First Moscow Medical University, Ministry of Health of Russia, Moscow, Russia.
A A
AA
Svistunov
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000375:Aging; D015415:Biomarkers / Q000097:blood; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology / Q000209:etiology; D018450:Disease Progression; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005500:Follow-Up Studies; D005819:Genetic Markers; D005966:Glucuronidase / Q000097:blood*; D006801:Humans; D015994:Incidence; D000090265:Klotho Proteins; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications* / Q000175:diagnosis; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D012426:Russia / Q000453:epidemiology; D055815:Young Adult
D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; C000717427:FGF23 protein, human; D005819:Genetic Markers; C422903:SOST protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins