Association of serum fetuin-A and fetuin-A gene polymorphism in relation to mineral and bone disorders in patients with chronic kidney disease

Dalia A Maharem,Salwa H Gomaa,Marwa K El Ghandor,Ehab I Mohamed,Khaled A Matrawy,Sameh S Zaytoun,Hanan M Nomeir

doi:10.1016/j.ejmhg.2013.07.003

Dalia A Maharem, Salwa H Gomaa + Show 5 more

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https://doi.org/10.1016/j.ejmhg.2013.07.003

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Abstract

Disorders of bone and mineral metabolism contribute to an increased prevalence of vascular calcification (VC) with its adverse clinical outcomes in patients with chronic kidney disease (CKD). The pathogenesis of VC is not fully understood. Fetuin-A is one of the inhibitors of calcification whose level is lowered in patients with CKD. In addition fetuin-A 256Ser/Ser (allele G) might affect serum fetuin-A levels. The aim of this work was to study the association between fetuin-A and its gene and VC and also with bone mineral density (BMD) in patients with CKD on conservative treatment, on maintenance of hemodialysis (HD) and those who underwent renal transplantation.This study included twenty eight CKD patients on HD, seventeen CKD patients on conservative treatment and twelve patients who underwent transplantation in addition to sixteen healthy controls. All were subjected to history taking, clinical examination, laboratory investigations including fasting serum glucose, urea, creatinine, albumin, lipid profile, C-reactive protein (CRP), estimated glomerular filteration rate (e-GFR), calcium, phosphorus, calcium by phosphorus product (Ca×PO4), intact parathyroid hormone (iPTH), alkaline phosphatase (Alk), fetuin-A and genotyping for the common functional polymorphisms on fetuin-A (Thr256Ser) using the Polymerase chain reaction (PCR) technique. Radiological examination included ultrasonography of carotid arteries and assessment of VC by plain X-ray and assessment of BMD.Serum calcium was lower, phosphorus, Ca×PO4, iPTH and Alk were higher in all patient groups than control. Fetuin-A was lower in all patient groups compared to controls. VC was detected in 39.2% HD patients, 29.4% patients on conservative treatment and 25% patients on transplantation. T-score of BMD was significantly lower in all patient groups than control. There was no statistically significant difference between patients and control groups according to the frequencies of the three fetuin-A genotypes (C→G) but the distribution of the fetuin-A (C→G); Thr256Ser gene polymorphisms in the studied subjects showed significant correlation with low serum fetuin-A levels. VC was associated with older age, male gender, longer HD duration, lower albumin, higher LDL-c, higher carotid plaques and lower T-score value of BMD.VC was evident in patients with CKD and it is related to atherosclerosis and lower BMD. Fetuin-A was lower in all patients with CKD with significant relation between serum fetuin-A level and its gene polymorphism but not with VC.

Highlights

Chronic kidney disease (CKD) is associated with increasing risk for cardiovascular disease (CVD) and cardiovascular events, even a slight reduction in glomerular filtration rate (GFR) is associated with a significant increase in cardiovascular risk [1,2]
chronic kidney disease–mineral and bone disorder (CKD–MBD) describes a triad of inter-related biochemical, bone and vascular abnormalities that have been linked with increased cardiovascular-related morbidity and mortality in patients with CKD and has been suggested as a non traditional risk factor for CVD in these patients [55,56]
The inhibitory role of fetuin-A on Vascular calcification (VC) may include the inhibition of calcium phosphate precipitation in the serum, binding of the bone derived hydroxyapatite and limitation of dedifferentiation and apoptosis of the vascular smooth muscle cells (VSMCs) [19,27,59]

Summary

Introduction

Chronic kidney disease (CKD) is associated with increasing risk for cardiovascular disease (CVD) and cardiovascular events, even a slight reduction in glomerular filtration rate (GFR) is associated with a significant increase in cardiovascular risk [1,2]. Up to 45% of pre-dialysis CKD patients may die before reaching end-stage renal disease (ESRD), with CVD being the leading cause of death with increasing risk in ESRD patients [3,4]. Despite an improvement in survival after renal transplantation, renal transplant recipients (RTRs) remain at an increased risk for CVD [5]. Vascular calcification (VC) is a strong independent risk factor for CV mortality [6]. Numerous risk factors have been reported, some of these are classic such as ageing, hypertension, diabetes, smoking and dyslipidemia [9,10]; certain others are more specific to CKD, such as mineral metabolism abnormalities, hyperphosphatemia, extreme parathyroid hormone, serum levels or excess administration of calcium salts and dialysis duration [10,11]

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