TY - JOUR

T1 - Plasma activin A rises with declining kidney function and is independently associated with mortality in patients with chronic kidney disease

AU - Nordholm, Anders

AU - Sørensen, Ida M.H.

AU - Bjergfelt, Sasha S.

AU - Fuchs, Andreas

AU - Kofoed, Klaus F.

AU - Landler, Nino E.

AU - Biering-Sørensen, Tor

AU - Carlson, Nicholas

AU - Feldt-Rasmussen, Bo

AU - Christoffersen, Christina

AU - Bro, Susanne

N1 - Publisher Copyright: © The Author (s) 2023. Published by Oxford University Press on behalf of the ERA.

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - activin A

KW - CKD-MBD

KW - MACE

KW - renal osteodystrophy

KW - vascular calcification

U2 - 10.1093/ckj/sfad238

DO - 10.1093/ckj/sfad238

M3 - Journal article

C2 - 38046005

AN - SCOPUS:85184777750

VL - 16

SP - 2712

EP - 2720

JO - Clinical Kidney Journal

JF - Clinical Kidney Journal

SN - 2048-8505

IS - 12

ER -