Vascular calcification relationship to vascular biomarkers and bone metabolism in advanced chronic kidney disease

Salam, Syazrah; Gallagher, Orla; Gossiel, Fatma; Paggiosi, Margaret; Eastell, Richard; Khwaja, Arif

Affiliations

¹Sheffield Kidney Institute, Sheffield Teaching Hospitals NHS Foundation Trust, United Kingdom

²Academic Unit of Bone Metabolism and Mellanby Centre for Bone Research, University of Sheffield, United Kingdom

Abstract and keywords

Background: Vascular calcification (VC) and renal osteodystrophy are important complications of advanced chronic kidney disease (CKD). High resolution peripheral quantitative computed tomography (HRpQCT) is able to assess bone microstructure in renal osteodystrophy and lower leg arterial calcification (LLAC) is usually seen as an incidental finding. LLAC can be a useful quantitative assessment of VC in CKD but the relationship between LLAC and vascular biomarkers and bone is unknown. We aimed to assess the relationship between LLAC and biomarkers, bone turnover and microstructure.

Methods: In this cross-sectional study, fasting blood samples were taken from 69 CKD stages 4-5D patients and 68 healthy controls. HRpQCT of distal tibia and radius were performed. 43 CKD patients had trans-iliac bone biopsy after tetracycline labelling.

Results: LLAC was more severe in CKD than controls (median [IQR] 1.043 [0.05–16.52] vs 0 [0–0.55] mgHA, p < 0.001). CKD patients with diabetes (28%) had significantly higher LLAC compared to non-diabetic CKD (median [IQR] 24.07 [3.42–61.30] vs 0.23 [0–3.78] mgHA, p < 0.001). LLAC mass in CKD correlated with serum phosphate (rho = 0.29, p < 0.05), calcium x phosphate product (rho = 0.31, p < 0.05), intact parathyroid hormone (rho = 0.38, p < 0.01), intact fibroblast growth factor-23 (iFGF23) (rho = 0.40, p = 0.001), total alkaline phosphatase (rho = 0.41, p < 0.001), bone alkaline phosphatase (rho = 0.29, p < 0.05), osteocalcin (rho = 0.32, p < 0.05), osteoprotegerin (rho = 0.40, p = 0.001) and dephosphorylated-uncarboxylated matrix Gla protein (rho = 0.31, p < 0.05). LLAC in CKD also correlated with worse distal tibia cortical bone mineral density, thickness and porosity. No association was found between LLAC and bone turnover, mineralization or volume on biopsy in CKD. In multivariate analysis, only age, diabetes, iPTH and iFGF23 were independently associated with LLAC in CKD.

Conclusions: High levels of PTH and FGF23, along with older age and the presence of diabetes may all play independent roles in the development of LLAC in advanced CKD.

Keywords: Arterial calcification; Dialysis; Renal osteodystrophy; Diabetes mellitus; FGF23

Links

DOI: 10.1016/j.bone.2020.115699

PubMed: 33091638

WoS: 000604734900011

History

Received: 2020-06-27

Revised: 2020-10-15

Accepted: 2020-10-15

Online: 2020-10-20

Cited Works (3)

Year	Entry
2009	KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease–mineral and bone disorder (CKD–MBD). Kidney Int. August 2009;76(suppl 113):S1-S130.
2020	Novel-Catin E, Pelletier S, Fouque D, Roux J-P, Chapurlat R, D'Haese P, Behets G, Evenepoel P, Nickolas TL, Lafage-Proust M-H. Quantitative histomorphometric analysis of halved iliac crest bone biopsies yield comparable ROD diagnosis as full 7.5mm wide samples. Bone. September 2020;138:115460.
1998	Bucay N, Sarosi I, Dunstan CR, Morony S, Tarpley J, Capparelli C, Scully S, Tan HL, Xu W, Lacey DL, Boyle WJ, Simonet WS. Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev. May 1998;12(9):1260-1268.