title: Galectin-3, Renal Function, and Clinical Outcomes: Results from the LURIC and 4D Studies.
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.
authors.affiliation: Division of Nephrology, Department of Internal Medicine 1 and Comprehensive Heart Failure Centre, University Hospital of Würzburg, Würzburg, Germany; drechsler_c@ukw.de.
authors.forename: Christiane
authors.initials: C
authors.lastname: Drechsler
authors.affiliation: Fifth Department of Medicine, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany;
authors.forename: Graciela
authors.initials: G
authors.lastname: Delgado
authors.affiliation: Division of Nephrology, Department of Internal Medicine 1 and Comprehensive Heart Failure Centre, University Hospital of Würzburg, Würzburg, Germany;
authors.forename: Christoph
authors.initials: C
authors.lastname: Wanner
authors.affiliation: Division of Nephrology, Department of Internal Medicine 1 and Comprehensive Heart Failure Centre, University Hospital of Würzburg, Würzburg, Germany;
authors.forename: Katja
authors.initials: K
authors.lastname: Blouin
authors.affiliation: Division of Endocrinology and Metabolism, Departments of Internal Medicine and.
authors.forename: Stefan
authors.initials: S
authors.lastname: Pilz
authors.affiliation: Cardiology, Medical University of Graz, Graz, Austria; Specialist Clinic for Rehabilitation PV Bad Aussee, Bad Aussee, Austria; Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Medizinische Klinik mit Schwerpunkt Kardiologie, Berlin, Germany;
authors.forename: Andreas
authors.initials: A
authors.lastname: Tomaschitz
authors.affiliation: Fifth Department of Medicine, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany;
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Kleber
authors.affiliation: Fifth Department of Medicine, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany;
authors.forename: Alexander
authors.initials: A
authors.lastname: Dressel
authors.affiliation: Division of Nephrology, Department of Internal Medicine 1 and Comprehensive Heart Failure Centre, University Hospital of Würzburg, Würzburg, Germany;
authors.forename: Christoph
authors.initials: C
authors.lastname: Willmes
authors.affiliation: Division of Nephrology, Department of Internal Medicine 1 and Comprehensive Heart Failure Centre, University Hospital of Würzburg, Würzburg, Germany;
authors.forename: Vera
authors.initials: V
authors.lastname: Krane
authors.affiliation: Fifth Department of Medicine, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany;
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Krämer
authors.affiliation: Fifth Department of Medicine, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany; Synlab Academy, Synlab Services GmbH, Mannheim, Germany;
authors.forename: Winfried
authors.initials: W
authors.lastname: März
authors.affiliation: Division of Nephrology, Department of Medicine, University Hospital Heidelberg, Heidelberg, Germany; and.
authors.forename: Eberhard
authors.initials: E
authors.lastname: Ritz
authors.affiliation: Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Wiek H
authors.initials: WH
authors.lastname: van Gilst
authors.affiliation: Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Pim
authors.initials: P
authors.lastname: van der Harst
authors.affiliation: Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: de Boer
mesh_terms: D000368:Aged; D001798:Blood Proteins; D002318:Cardiovascular Diseases / Q000401:mortality*; D002423:Cause of Death; D003928:Diabetic Nephropathies / Q000097:blood* / Q000401:mortality / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D037502:Galectin 3 / Q000097:blood*; D037161:Galectins; D005858:Germany / Q000453:epidemiology; D005919:Glomerular Filtration Rate; D006801:Humans; D007239:Infections / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000401:mortality / Q000628:therapy; D012720:Severity of Illness Index
chemical_list: D001798:Blood Proteins; D037502:Galectin 3; D037161:Galectins; C428445:LGALS3 protein, human
keywords: CKD; cardiovascular disease; hemodialysis