Gender-Related Differences in Chronic Kidney Disease-Associated Vascular Calcification Risk and Potential Risk Mediators: A Scoping Review

Abstract

Vascular calcification (VC) involves the deposition of calcium apatite in vascular intima or media. Individuals of advanced age, having diabetes mellitus or chronic kidney disease (CKD) are particularly at risk. The pathogenesis of CKD-associated VC evolves considerably. The core driver is the phenotypic change involving vascular wall constituent cells toward manifestations similar to that undergone by osteoblasts. Gender-related differences are observed regarding the expressions of osteogenesis-regulating effectors, and presumably the prevalence/risk of CKD-associated VC exhibits gender-related differences as well. Despite the wealth of data focusing on gender-related differences in the risk of atherosclerosis, few report whether gender modifies the risk of VC, especially CKD-associated cases. We systematically identified studies of CKD-associated VC or its regulators/modifiers reporting data about gender distributions, and extracted results from 167 articles. A significantly higher risk of CKD-associated VC was observed in males among the majority of original investigations. However, substantial heterogeneity exists, since multiple large-scale studies yielded neutral findings. Differences in gender-related VC risk may result from variations in VC assessment methods, the anatomical segments of interest, study sample size, and even the ethnic origins of participants. From a biological perspective, plausible mediators of gender-related VC differences include body composition discrepancies, alterations involving lipid profiles, inflammatory severity, diversities in matrix Gla protein (MGP), soluble Klotho, vitamin D, sclerostin, parathyroid hormone (PTH), fibroblast growth factor-23 (FGF-23), and osteoprotegerin levels. Based on our findings, it may be inappropriate to monotonously assume that male patients with CKD are at risk of VC compared to females, and we should consider more background in context before result interpretation.

Comparison of CT acquired cardiac valvular calcification scores in hemodialysis and peritoneal dialysis patients undergoing open heart surgery

“…Others attribute the difference to hormonal variability such that there is a clear role for androgens in the promotion of calcific nodule and reactive oxygen species formation [26] . In an in-depth review on whether chronic kidney disease modifies vascular calcification risk, heterogeneous conclusions were found such that some large scale studies yielded neutral results with a few noting higher vascular calcification risk in females, similar to our study [27] . Interestingly, our results for the prevalence of mitral and aortic calcification are concordant of those published in patients without ESRD.…”

Comparative Analysis of Vascular Calcification Risk Factors in Pre-Hemodialysis and Prevalent Hemodialysis Adult Patients: Insights into Calcification Biomarker Associations and Implications for Intervention Strategies in Chronic Kidney Disease

“…The patients differed in age in favor of the pre-HD group, and older age was a predictor of VC. In the pre-HD group, a higher prevalence of VC was found in men, which is consistent with some studies in patients with CKD [42]. According to previously published data, potential contributors to the observed gender-related differences involve hormonal, lifestyle, genetic, disease duration factors, pericardial/total fat, lipid profile, inflammatory status, variations in matrix Gla protein (MGP), soluble Klotho, vitamin D, sclerostin, iPTH, FGF 23, and osteoprotegerin levels [42].…”

Chest radiography deep radiomics-enabled aortic arch calcification interpretation across different populations

“…CKD elevates the risk of VC through the adverse influences posed by uremic toxins, oxidative stress, chronic inflammation, divalent ion/mineral-regulating hormone imbalances, declining anti-calcific factors, and epigenome alterations. 22 , 23 The multitude of compounding risk factors in the CKD micr-environment accelerates biologic aging and aggravates VC; on the other hand, older adults also tend to have low-grade chronic inflammation and organ senescence, accounting for their susceptibility of developing VC. 24 We presume that CKD encompasses a relatively wider range of VC risk factors compared to chronological aging, and this may partially explain the more severe VC and more extensive VC tree involvement in the former.…”