title: High Mobility Group Box Protein-1 correlates with renal function in chronic kidney disease (CKD).
abstract: Chronic kidney disease (CKD) is associated with inflammation and malnutrition and carries a markedly increased risk of cardiovascular disease (CVD). High Mobility Group Box Protein-1 (HMGB-1) is a 30-kDa nuclear and cytosolic protein known as a transcription and growth factor, recently identified as a proinflammatory mediator of tissue injury. Recent data implicates HMGB-1 in endotoxin lethality, rheumatoid arthritis, and atherosclerosis. The aim of this post-hoc, cross-sectional study was to determine whether HMGB-1 serum levels are elevated in CKD patients. The study groups were categorized as follows: 110 patients starting dialysis defined as CKD 5; 67 patients with moderately to severely reduced renal function or CKD 3-4; and 48 healthy controls. High-sensitivity C-reactive-protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor (TNF), serum-albumin (S-albumin), hemoglobin A(1c) (HbA(1c)), hemoglobin, subjective global nutritional assessment (SGA), and glomerular filtration rate (GFR) were analyzed. Kruskal-Wallis test was used to compare groups and Spearman's rank correlation test was used for continuous variables. HMGB-1, measured by Western blot, was significantly (P < 0.001) elevated in CKD 5 (146.7 +/- 58.6 ng/mL) and CKD 3-4 (85.6 +/- 31.8) compared with controls (10.9 +/- 10.5). HMGB-1 levels were correlated positively with TNF (Rho = 0.52; P < 0.001), hs-CRP (Rho = 0.38; P < 0.001), IL-6 (Rho = 0.30; P < 0.001), HbA(1c) (Rho = 0.14; P = 0.02) and SGA (Rho = 0.21; P = 0.002) and negatively correlated with GFR (Rho = -0.69; P = 0.0001), Hb (Rho = -0.60; P < 0.001), S-albumin (Rho = -0.31; P < 0.001). The current study has revealed that HMGB-1 is elevated significantly in CKD patients and correlates with GFR as well as markers of inflammation and malnutrition. Future studies may delineate whether HMGB-1 is also a marker of disease activity and severity as well as a predictor of outcome in CKD.
authors.affiliation: Feinstein Institute for Medical Research, North Shore University Hospital-LIJ Health System, Manhasset, New York, USA. Annette.Bruchfeld@ki.se
authors.forename: Annette
authors.initials: A
authors.lastname: Bruchfeld
authors.forename: Abdul Rashid
authors.initials: AR
authors.lastname: Qureshi
authors.forename: Bengt
authors.initials: B
authors.lastname: Lindholm
authors.forename: Peter
authors.initials: P
authors.lastname: Barany
authors.forename: Lihong
authors.initials: L
authors.lastname: Yang
authors.forename: Peter
authors.initials: P
authors.lastname: Stenvinkel
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Tracey
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D003430:Cross-Sectional Studies; D003627:Data Interpretation, Statistical; D005260:Female; D005919:Glomerular Filtration Rate; D024243:HMGB1 Protein / Q000097:blood* / Q000235:genetics; D006801:Humans; D007668:Kidney / Q000502:physiology*; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged
chemical_list: D015415:Biomarkers; D024243:HMGB1 Protein