The Novel Bone Alkaline Phosphatase Isoform B1x Is Associated with Improved 5-Year Survival in Chronic Kidney Disease.
Mathias HaarhausAnders FernströmAbdul Rashid QureshiPer MagnussonPublished in: Nutrients (2021)
Circulating alkaline phosphatase (ALP) is an independent cardiovascular risk marker. Serum bone ALP (BALP) isoforms indicate bone turnover and comprise approximately 50% of total circulating ALP. In chronic kidney disease (CKD), mortality is highest in patients with increased ALP and BALP and low bone turnover. However, not all low bone turnover states are associated with increased mortality. Chronic inflammation and oxidative stress, features of protein energy wasting syndrome, induce cardiovascular BALP activity and fibro-calcification, while bone turnover is suppressed. Circulating BALP isoform B1x is associated with low ALP and low bone turnover and has been exclusively detected in CKD. We investigated the association of serum B1x with survival, abdominal aortic calcification (AAC) score, and aortic pulse wave velocity (PWV) in CKD. Serum ALP, BALP isoforms, parathyroid hormone (PTH), PWV, and AAC were measured repeatedly over 2 years in 68 prevalent dialysis patients. Mortality was assessed after 5 years. B1x was detected in 53 patients. A competing risk analysis revealed an association of B1x with improved 5-year survival; whereas, baseline PWV, but not AAC score, predicted mortality. However, PWV improved in 26 patients (53%), and B1x was associated with variation of PWV over time ( p = 0.03). Patients with B1x had lower PTH and total ALP, suggesting an association with lower bone turnover. In conclusion, B1x is associated with time-varying PWV, lower circulating ALP, and improved survival in CKD, and thus may be an indicator of a reduced cardiovascular risk profile among patients with low bone turnover.
Keyphrases
- bone mineral density
- chronic kidney disease
- end stage renal disease
- postmenopausal women
- body composition
- oxidative stress
- ejection fraction
- soft tissue
- bone loss
- newly diagnosed
- peritoneal dialysis
- cardiovascular events
- prognostic factors
- bone regeneration
- blood pressure
- cardiovascular disease
- heart failure
- free survival
- coronary artery disease
- aortic valve
- coronary artery
- left ventricular
- pulmonary arterial hypertension
- small molecule
- pulmonary hypertension
- atrial fibrillation
- high resolution
- single molecule
- amino acid
- high speed