Galectin-3, Renal Function, and Clinical Outcomes: Results from the LURIC and 4D Studies

J Am Soc Nephrol. 2015 Sep;26(9):2213-21. doi: 10.1681/ASN.2014010093. Epub 2015 Jan 7.

Abstract

Galectin-3 has been linked to incident renal disease, experimental renal fibrosis, and nephropathy. However, the association among galectin-3, renal function, and adverse outcomes has not been described. We studied this association in two large cohorts of patients over a broad range of renal function. We measured galectin-3 concentrations in baseline samples from the German Diabetes mellitus Dialysis (4D) study (1168 dialysis patients with type 2 diabetes mellitus) and the Ludwigshafen Risk and Cardiovascular Health (LURIC) study (2579 patients with coronary angiograms). Patients were stratified into three groups: eGFR of ≥90 ml/min per 1.73 m(2), 60-89 ml/min per 1.73 m(2), and <60 ml/min per 1.73 m(2). We correlated galectin-3 concentrations with demographic, clinical, and biochemical parameters. The association of galectin-3 with clinical end points was assessed by Cox proportional hazards regression within 10 years (LURIC) or 4 years (4D) of follow-up. Mean±SD galectin-3 concentrations were 12.8±4.0 ng/ml (eGFR≥90 ml/min per 1.73 m(2)), 15.6±5.4 ng/ml (eGFR 60-89 ml/min per 1.73 m(2)), 23.1±9.9 ng/ml (eGFR<60 ml/min per 1.73 m(2)), and 54.1±19.6 ng/ml (dialysis patients of the 4D study). Galectin-3 concentration was significantly associated with clinical end points in participants with impaired kidney function, but not in participants with normal kidney function. Per SD increase in log-transformed galectin-3 concentration, the risks of all-cause mortality, cardiovascular mortality, and fatal infection increased significantly. In dialysis patients, galectin-3 was associated with the combined end point of cardiovascular events. In conclusion, galectin-3 concentrations increased with progressive renal impairment and independently associated with cardiovascular end points, infections, and all-cause death in patients with impaired renal function.

Keywords: CKD; cardiovascular disease; hemodialysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blood Proteins
  • Cardiovascular Diseases / mortality*
  • Cause of Death
  • Diabetic Nephropathies / blood*
  • Diabetic Nephropathies / mortality
  • Diabetic Nephropathies / therapy
  • Female
  • Follow-Up Studies
  • Galectin 3 / blood*
  • Galectins
  • Germany / epidemiology
  • Glomerular Filtration Rate*
  • Humans
  • Infections / mortality*
  • Male
  • Middle Aged
  • Renal Dialysis
  • Renal Insufficiency, Chronic / blood*
  • Renal Insufficiency, Chronic / mortality
  • Renal Insufficiency, Chronic / therapy
  • Severity of Illness Index

Substances

  • Blood Proteins
  • Galectin 3
  • Galectins
  • LGALS3 protein, human