{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Laucyte-Cibulskiene A"],"funding":["hjärt-lungfonden","Austrian Science Fund FWF","canadian institutes of health research","njurfonden","scientific independence of young researcher program of the italian ministry of university","novo nordisk postdoctoral fellowship","“la caixa” foundation","vetenskapsrådet","Karolinska Institute"],"pagination":["50"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8444580"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["12(1)"],"pubmed_abstract":["<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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."],"journal":["Biology of sex differences"],"pubmed_title":["Role of GDF-15, YKL-40 and MMP 9 in patients with end-stage kidney disease: focus on sex-specific associations with vascular outcomes and all-cause mortality."],"pmcid":["PMC8444580"],"funding_grant_id":["20160384","RBSI14HNVT","I 4209","FWF","2018-00932","100010434","GNP161904","I4209"],"pubmed_authors":["Kautzky-Willer A","GOING-FWD Consortium","Herrero MT","Ripsweden J","Soderberg M","Stenvinkel P","Laucyte-Cibulskiene A","Raparelli V","Kublickiene K","Ebert T","Pilote L","Tosti G","Hernandez L","Brismar TB","Norris CM","Ward LJ","Tucci C"],"additional_accession":[]},"is_claimable":false,"name":"Role of GDF-15, YKL-40 and MMP 9 in patients with end-stage kidney disease: focus on sex-specific associations with vascular outcomes and all-cause mortality.","description":"<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Sep","modification":"2025-04-26T02:54:26.669Z","creation":"2022-02-11T11:04:01.31Z"},"accession":"S-EPMC8444580","cross_references":{"pubmed":["34526107"],"doi":["10.1186/s13293-021-00393-0"]}}