Plasma activin A rises with declining kidney function and is independently associated with mortality in patients with chronic kidney disease

Anders Nordholm*, Ida M.H. Sørensen, Sasha S. Bjergfelt, Andreas Fuchs, Klaus F. Kofoed, Nino E. Landler, Tor Biering-Sørensen, Nicholas Carlson, Bo Feldt-Rasmussen, Christina Christoffersen, Susanne Bro

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

5 Citationer (Scopus)
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Abstract

Background
Plasma (p-)activin A is elevated in chronic kidney disease–mineral and bone disorder (CKD-MBD). Activin A inhibition ameliorates CKD-MBD complications (vascular calcification and bone disease) in rodent CKD models. We examined whether p-activin A was associated with major adverse cardiovascular events (MACE), all-cause mortality and CKD-MBD complications in CKD patients.

Methods
The study included 916 participants (741 patients and 175 controls) from the prospective Copenhagen CKD cohort. Comparisons of p-activin A with estimated glomerular filtration rate (eGFR), coronary and thoracic aorta Agatston scores, and bone mineral density (BMD) were evaluated by univariable linear regression using Spearman's rank correlation, analysis of covariance and ordinal logistic regression with adjustments. Association of p-activin A with rates of MACE and all-cause mortality was evaluated by the Aalen–Johansen or Kaplan–Meier estimator, with subsequent multiple Cox regression analyses.

Results
P-activin A was increased by CKD stage 3 (124–225 pg/mL, P < .001) and correlated inversely with eGFR (r = −0.53, P < 0.01). P-activin A was associated with all-cause mortality [97 events, hazard ratio 1.55 (95% confidence interval 1.04; 2.32), P < 0.05] after adjusting for age, sex, diabetes mellitus (DM) and eGFR. Median follow-up was 4.36 (interquartile range 3.64–4.75) years. The association with MACE was not significant after eGFR adjustment. Agatston scores and BMD were not associated with p-activin A.

Conclusion
P-activin A increased with declining kidney function and was associated with all-cause mortality independently of age, sex, DM and eGFR. No association with MACE, vascular calcification or BMD was demonstrated.
OriginalsprogEngelsk
TidsskriftClinical Kidney Journal
Vol/bind16
Udgave nummer12
Sider (fra-til)2712-2720
Antal sider9
ISSN2048-8505
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
This study was supported by the Augustinus Foundation, Novo Nordisk Foundation, and The Capital Region of Denmark.

Publisher Copyright:
© The Author (s) 2023. Published by Oxford University Press on behalf of the ERA.

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