ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: SA-PO188

Plasma Activin A Rises Through CKD Stages but Is Unrelated to Vascular Calcification and Cardiovascular Events

Session Information

Category: Bone and Mineral Metabolism

  • 402 Bone and Mineral Metabolism: Clinical

Authors

  • Nordholm, Anders, Dept. of Nephrology, Rigshospitalet, Copenhagen, Denmark
  • Sørensen, Ida Maria Hjelm, Dept. of Nephrology, Rigshospitalet, Copenhagen, Denmark
  • Bjergfelt, Sasha Saurbrey, Dept. of Nephrology, Rigshospitalet, Copenhagen, Denmark
  • Fuchs, Andreas, Dept. of Cardiology, Rigshospitalet, Copenhagen, Denmark
  • Kofoed, Klaus Fuglsang, Dept. of Cardiology, Rigshospitalet, Copenhagen, Denmark
  • Landler, Nino Emanuel, Dept. of Cardiology, Herlev & Gentofte Hospital, Copenhagen, Denmark
  • Biering-Sørensen, Tor Emanuel, Dept. of Cardiology, Herlev & Gentofte Hospital, Copenhagen, Denmark
  • Feldt-Rasmussen, Bo, Dept. of Nephrology, Rigshospitalet, Copenhagen, Denmark
  • Christoffersen, Christina, Dept. of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark
  • Bro, Susanne, Dept. of Nephrology, Rigshospitalet, Copenhagen, Denmark
Background

Activin A (ActA) is a hormone related to CKD and mineral and bone disorder (MBD). Animal studies show that ActA is elevated in CKD and that ActA signaling inhibition ameliorates renal fibrosis, vascular calcification (VC) and bone disease in CKD. We examined plasma ActA (p-ActA) levels in a large cohort of CKD and controls and determined if p-ActA was associated with radiographic measures of VC and bone mineral density (BMD) as well as cardiovascular events (MACE).

Methods

Prospective cohort study. Patients with CKD stages 1–5 not on dialysis (N=741) and age-/sex-matched healthy controls (ctl) (N=175). Baseline p-ActA was measured by ELISA (DAC00B, R&D). VC in coronary arteries (CA) and thoracic aorta (TA) was determined by non-contrast 320-multidetector CT scans, quantified by Agatston score. Thoracic BMD (Th7-9) in mg/cm2 was assessed from the CT scans using a Phantom. Comparison between p-ActA and continuous variables were done by linear regression and Spearmans correlation. Comparing p-ActA to CKD stage, Agatston-, and BMD groups was done by ANOVA. MACE (median follow-up 4±1 yrs) was assessed and related to p-ActA quartiles using Kaplan-Meier and Cox regression.

Results

P-ActA is inversely correlated to eGFR (r=-0.53, p<0.001), and rises continuously from ctl and through CKD stages (ctl 136±71pg/mL, CKD1 148±90, CKD2 175±106, CKD3 239±120, CKD4 330±218, CKD5ND 397±202), significant from CKD3 to CKD5 (p<0.001). P-ActA was correlated with Agatston score in CA (r=0.23, p<0.01) but not in TA of CKD patients. P-ActA was significantly increased in the Agatston score >400 group from 219±166 to 285±144 (p<0.01) in CA, and from 206±135 to 280±146 (p<0.01) in TA. The associations lost significance when adjusted for either age or eGFR. Thoracic BMD was not correlated to p-ActA and there was no difference in p-ActA levels when stratified into BMD groups groups of very low (<80), low (80-120), and normal (>120) BMD. The HR of MACE in the highest quartile of p-ActA (>289pg/mL) was 3.98 [2.39-6.61], but 1.67 [0.97-2.88] when adjusting for eGFR.

Conclusion

Plasma activin A rises with declining kidney function but was not independently associated with radiographic parameters of BMD, VC or MACE.