Plasma syndecan-1 in hemodialysis patients associates with survival and lower markers of volume status

Am J Physiol Renal Physiol. 2019 Jan 1;316(1):F121-F127. doi: 10.1152/ajprenal.00252.2018. Epub 2018 Oct 31.

Abstract

Syndecan-1, a transmembrane heparan sulfate proteoglycan, associates with renal and cardiovascular functioning. We earlier reported syndecan-1 to be involved in renal tubular regeneration. We now examined plasma values of syndecan-1 in a hemodialysis cohort and its association with volume and inflammatory and endothelial markers in addition to outcome. Eighty-four prevalent hemodialysis patients were evaluated for their plasma syndecan-1 levels by ELISA before the start of hemodialysis, as well as 60, 180, and 240 min after start of dialysis. Patients were divided into sex-stratified tertiles based on predialysis plasma syndecan-1 levels. We studied the association between plasma levels of syndecan-1 and volume, inflammation, and endothelial markers and its association with cardiovascular events and all-cause mortality using Kaplan-Meier curves and Cox regression analyses with adjustments for gender, age, diabetes, and dialysis vintage. Predialysis syndecan-1 levels were twofold higher in men compared with women ( P = 0.0003). Patients in the highest predialysis plasma syndecan-1 tertile had a significantly higher ultrafiltration rate ( P = 0.034) and lower plasma values of BNP ( P = 0.019), pro-ANP ( P = 0.024), and endothelin ( P < 0.0001) compared with the two lower predialysis syndecan-1 tertiles. No significant associations with inflammatory markers were found. Cox regression analysis showed that patients in the highest syndecan-1 tertile had significantly less cardiovascular events and better survival compared with the lowest syndecan-1 tertile ( P = 0.02 and P = 0.005, respectively). In hemodialysis patients, higher plasma syndecan-1 levels were associated with lower concentrations of BNP, pro-ANP, and endothelin and with better patient survival. This may suggest that control of volume status in hemodialysis patients allows an adaptive tissue regenerative response as reflected by higher plasma syndecan-1 levels.

Keywords: hemodialysis; inflammation; syndecan-1; ultrafiltration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Atrial Natriuretic Factor / blood
  • Biomarkers / blood
  • Endothelins / blood
  • Female
  • Humans
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / mortality
  • Kidney Failure, Chronic / physiopathology
  • Kidney Failure, Chronic / therapy*
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Renal Dialysis* / adverse effects
  • Renal Dialysis* / mortality
  • Risk Assessment
  • Risk Factors
  • Syndecan-1 / blood*
  • Time Factors
  • Treatment Outcome
  • Up-Regulation
  • Water-Electrolyte Balance*

Substances

  • Biomarkers
  • Endothelins
  • NPPA protein, human
  • SDC1 protein, human
  • Syndecan-1
  • Natriuretic Peptide, Brain
  • Atrial Natriuretic Factor