Abstract
Background
Sex differences are underappreciated in the current understanding of cardiovascular disease (CVD) in association with chronic kidney disease (CKD). A hallmark of CKD is vascular aging that is characterised, amongst others, by; systemic inflammation, microbiota disbalance, oxidative stress, and vascular calcification—features linked to atherosclerosis/arteriosclerosis development. Thus, it is the necessary to introduce novel biomarkers related to athero-/arteriosclerotic damage for better assessment of vascular ageing in patients CKD. However, little is known about the relationship between uraemia and novel CVD biomarkers, such as growth differentiation factor-15 (GDF-15), cartilage glycoprotein-39 (YKL-40) and matrix metalloproteinase-9 (MMP-9). Therefore, we hypothesise that there are sex-specific relationships between GDF-15, YKL-40, MMP-9 levels in end-stage kidney disease (ESKD) patients in relation to gut microbiota, vascular calcification, inflammation, comorbidities, and all-cause mortality.
Methods
ESKD patients, males (n = 151) and females (n = 79), not receiving renal replacement therapy were selected from two ongoing prospective ESKD cohorts. GDF-15, YKL-40 and MMP9 were analysed using enzyme-linked immunosorbent assay kits. Biomarker levels were analysed in the context of gut microbiota-derived trimethylamine N-oxide (TMAO), vascular calcification, inflammatory response, oxidative stress, comorbidities, and all-cause mortality.
Results
Increased GDF-15 correlated with higher TMAO in females only, and with higher coronary artery calcification and IL-6. In females, diabetes was associated with elevated GDF-15 and MMP-9, whilst males with diabetes only had elevated GDF-15. No associations were found between biomarkers and CVD comorbidity. Deceased males and females had higher GDF-15 concentrations (p = 0.01 and p < 0.001, respectively), meanwhile only YKL-40 was increased in deceased males (p = 0.02).
Conclusions
In conclusion, in males GDF-15 and YKL-40 were related to vascular calcification, inflammation, and oxidative stress, whilst in females GDF-15 was related to TMAO. Increased levels of YKL-40 and GDF-15 in males, and only GDF-15 in females, were associated with all-cause mortality. Our findings suggest that sex-specific associations of novel CVD biomarkers have a potential to affect development of cardiovascular complications in patients with ESKD.
SP572WHAT ARE THE DETERMINING FACTORS OF VASCULAR CALCIFICATION AND IS THERE ANY RELATIONSHIP BETWEEN VASCULAR CALCIFICATION, ARTERIAL STIFFNESS, FIBROBLAST GROWTH FACTOR-23 AND FETUIN-A IN END-STAGE KIDNEY DISEASE PATIENTS ON REGULAR HEMODIALYSIS?