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.

Autor:	Laucyte-Cibulskiene A; Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.; Department of Nephrology, Lund University, Skåne University Hospital, Malmö, Sweden., Ward LJ; Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden., Ebert T; Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden., Tosti G; Institute of Internal Medicine, Catholic University of Rome, Fondazione Policlinico Gemelli IRCCS, Rome, Italy., Tucci C; Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Florence, Italy., Hernandez L; Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden., Kautzky-Willer A; Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria., Herrero MT; Clinical and Experimental Neuroscience, Institutes for Aging Research and Bio-Health Research of Murcia, School of Medicine, University of Murcia, Murcia, Spain., Norris CM; University of Alberta, Faculty of Nursing, Edmonton, AB, Canada.; Cardiovascular and Stroke Strategic Clinical Network, Alberta Health Services, Edmonton, AB, Canada., Pilote L; Division of Clinical Epidemiology, Research Institute of McGill University Health Centre, McGill University, Montreal, QC, Canada., Söderberg M; Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Göteborg, Sweden., Brismar TB; Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.; Department of Radiology, Karolinska University Hospital in Huddinge, Stockholm, Sweden., Ripsweden J; Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.; Department of Radiology, Karolinska University Hospital in Huddinge, Stockholm, Sweden., Stenvinkel P; Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden., Raparelli V; University of Alberta, Faculty of Nursing, Edmonton, AB, Canada.; Department of Translational Medicine, University of Ferrara, Ferrara, Italy., Kublickiene K; Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden. karolina.kublickiene@ki.se.; Division of Renal Medicine, Department for Clinical Science, Intervention & Technology, Karolinska University Hospital-Flemingsberg Campus, 14186, Stockholm, Sweden. karolina.kublickiene@ki.se.
Jazyk:	angličtina
Zdroj:	Biology of sex differences [Biol Sex Differ] 2021 Sep 15; Vol. 12 (1), pp. 50. Date of Electronic Publication: 2021 Sep 15.
DOI:	10.1186/s13293-021-00393-0
Abstrakt:	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. (© 2021. The Author(s).)
Databáze:	MEDLINE
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