Vascular Calcification Is Associated with Fetuin-A and Cortical Bone Porosity in Stone Formers

J Pers Med. 2022 Jul 10;12(7):1120. doi: 10.3390/jpm12071120.

Abstract

Background: Nephrolithiasis has been associated with bone loss and vascular calcification (VC), reflecting abnormal extraosseous calcium deposition. Fetuin-A (Fet-A) acts as a potent inhibitor of ectopic mineralization. The aim of the present study was to evaluate the prevalence of VC in stone formers (SF) and non-stone formers (NSF) and to investigate potential determinants of VC among SF, including circulating levels of Fet-A and bone microarchitecture parameters. Methods: Abdominal aortic calcification (AAC) was assessed using available computed tomography in SF and in age-, sex-, and BMI-matched NSF (potential living kidney donors). Serum Fet-A was measured in stored blood samples from SF. Bone microarchitecture parameters were obtained as a post hoc analysis of a cross-sectional cohort from young SF evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT). Results: A total of 62 SF (38.0 [28.0−45.3] years old) and 80 NSF (40.0 [37.0−45.8] years old) were included. There was no significant difference in AAC scores between SF and NSF. However, when dividing SF according to mean AAC score, below <5.8% (n = 33) or above ≥5.8% (n = 29), SF with higher AAC presented significantly higher BMI and tibial cortical porosity (Ct.Po) and significantly lower serum HDL, klotho, Fet-A, and eGFR. Urinary calcium did not differ between groups, but fractional excretion of phosphate was higher in the former. Upon multivariate regression, BMI, serum Fet-A, and tibial Ct.Po remained independently associated with AAC. Conclusions: This study suggests an association between reduced circulating Fet-A levels and increased bone Ct.Po with VC in SF.

Keywords: HR-pQCT; bone; fetuin-A; kidney stones; nephrolithiasis; vascular calcification.

Grants and funding

This study was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (grant 2016/25359-0), Conselho Nacional de Desenvolvimento Científico e Tecnológico, grant 309045/2018-5 (I.P.H.), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—CAPES (F.G.R.), and Fundação Oswaldo Ramos—Hospital do Rim (HRIM).