The Impact of Osteocalcin, Osteoprotegerin and Osteopontin on Arterial Stiffness in Chronic Renal Failure Patients on Hemodialysis

Abstract

Background/Aims: This cross-sectional study was designed to assess the relationship between vascular stiffness (VS) and bone-related proteins involved in the development of arteriosclerosis in patients on regular hemodialysis (HD). Methods: 68 consecutive patients in stable clinical condition who received regular HD in the FMC Dialysis Center, Pécs were included. VS parameters (carotid-femoral pulse wave velocity – PWV, aortic augmentation index - AIx) were determined by applanation tonometry (SphygmoCor, AtCor Medical, Sidney) and the routine latoratory test were completed with measurements of osteocalcin (OC), osteopontin (OP) and osteoprotegerin (OPG) by using commercially available ELISA kits. 35 heathcare workers served as controls. Results: In patients on regular HD PWV markedly increased and there was several-fold elevation in the interrelated bone-specific proteins (OC, OP, OPG). PWV was found to be independently associated only with OC (β:-0.25, p<0.029) and age (r=0.411,p<0.000), but risk factors for arterial calcification had significant impact on OC (systolic blood pressure, hsCRP, BMI), OPG (age, BMI) and OP (LDL-cholesterol). Conclusion: Except for OC, our results failed to document direct association of vascular lesion with OP and OPG, therefore their high circulating levels may be an epiphenomenon or they may have counter-regulatory role to attenuate the uremic calcification process.

Serum Osteocalcin Level is Negatively Associated with Vascular Reactivity Index by Digital Thermal Monitoring in Kidney Transplant Recipients

“…Osteocalcin, a γ-carboxyglutamic acid containing noncollagenous protein, has been identified to be secreted by osteoblasts, and they are usually stored in bones, bound to hydroxyapatite and calcium; in its undercarboxylated form, it is released into circulation. It is now generally accepted that impaired bone metabolism may lead to the development of vascular calcification; this concept is consistent with the observation that bone loss is associated with increased vascular calcification and increased incidence of cardiovascular events [9]. Vascular smooth muscle cells play an important role in the pathogenesis of vascular calcification: they change from being contractile to being osteogenic and express osteogenic cell markers, including osteocalcin [10].…”

Elevated serum levels of bone sialoprotein during ICU treatment predict long-term mortality in critically ill patients

“…While a functional importance of BSP in cancer development has been extensively demonstrated, the role of BSP in critical illness and sepsis has previously not been elucidated. In contrast, we and others have previously shown an important role of another SIBLING protein, osteopontin (OPN), in critical illness 6 , 34 , sepsis 35 , 36 , renal 37 and heart failure 38 . Like osteopontin, BSP has been shown to be upregulated in renal failure 39 .…”

Nuevos biomarcadores usados en el diagnóstico del daño renal en condiciones de estrés oxidativo

“…Sin embargo, la aparición de estas proteínas en la excreción renal se encuentra aumentada en respuesta a la lesión renal, por lo tanto, son biomoléculas blanco en la predicción de esta patología. 9…”

“…16 La OPG se expresa en una variedad de tejidos, incluidos los endoteliales vasculares. 9 En consecuencia, la OPG tiene doble función de protección: promueve la mineralización esquelética, pero previene la mineralización en el tejido vascular. 17 Los niveles elevados de OPG circulantes en pacientes con enfermedades cardiovasculares y renales crónicas, se asocian de forma independiente con la mortalidad por causa del cáncer y la aterosclerosis.…”

“…19 Hoy en día, todavía se discute acerca de la vía de expresión de la OPG en la lesión vascular, así como no está clara la relación de los altos niveles de OPG circulante con la regulación atenuante en el proceso de calcificación. 9…”