title: Plasma Pentosidine and Its Association with Mortality in Patients with Chronic Kidney Disease.
abstract: BACKGROUND
  Circulating advanced glycated end-products (AGEs) including pentosidine accumulating in chronic kidney disease (CKD) patients due to retention and increased formation are thought to contribute to cardiovascular disease (CVD). Here we evaluated factors linked to increased plasma pentosidine and its association with mortality in patients with different stages of CKD and undergoing different treatments.
  
  
  METHODS
  Plasma pentosidine, biomarkers of inflammation, oxidative stress and nutritional status were investigated in CKD 1-2 (n = 37), CKD 3-4 (n = 54), CKD 5 non-dialyzed (CKD5-ND; n = 386), peritoneal dialysis (PD; n = 74) and hemodialysis (HD; n = 195) patients. Factors predicting plasma pentosidine were analysed by multivariate regression analysis and mortality risk was assessed by GENMOD procedure.
  
  
  RESULTS
  Plasma pentosidine levels, which were higher in CKD5-ND, PD and HD groups than in CKD 1-2 group, were significantly lower in PD than in HD patients, and not different between PD patients and CKD5-ND patients. Pentosidine associated inversely with glomerular filtration rate (GFR), and additionally in PD with 8-hydroxy-2'-deoxyguanosine (8-OHdG), and interleukin 6 (IL-6); in HD with age, IL-6 and body mass index (BMI); in CKD5-ND with age, 8-OHdG, IL-6, high-sensitive C-reactive protein (hsCRP), and soluble vascular cell adhesion protein-1 (sVCAM-1); in CKD 3-4 with 8-OHdG and sVCAM-1; and in CKD 1-2 with age and sVCAM-1. In multivariate analysis, age (one standard deviation, 1-SD higher), malnutrition (subjective global assessment, SGA), oxidative stress (8-OHdG, 1-SD higher), and belonging to CKD5-ND, HD and PD cohorts associated with 1-SD higher pentosidine. In GENMOD, 1-SD higher pentosidine independently predicted all-cause mortality (relative risk, RR = 1.04; 95% confidence interval, CI, 1.01-1.08, p = 0.01) and CVD mortality (RR = 1.03; 95% CI, 1.01-1.06, p = 0.03) after adjusting for all confounders.
  
  
  CONCLUSIONS
  Plasma pentosidine is markedly elevated in CKD and associates with low GFR, oxidative stress and inflammation, and is an independent predictor of mortality in CKD patients.
authors.affiliation: Renal Medicine and Baxter Novum, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anna
authors.identifier: http://orcid.org/0000-0002-4675-2908
authors.initials: A
authors.lastname: Machowska
authors.affiliation: Renal Medicine and Baxter Novum, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jia
authors.initials: J
authors.lastname: Sun
authors.affiliation: Renal Medicine and Baxter Novum, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Abdul Rashid
authors.initials: AR
authors.lastname: Qureshi
authors.affiliation: Renal Medicine and Baxter Novum, Karolinska Institutet, Stockholm, Sweden.|Department of Urology, Yamaguchi University, Ube, Yamaguchi, Japan.
authors.forename: Naohito
authors.initials: N
authors.lastname: Isoyama
authors.affiliation: Renal Medicine and Baxter Novum, Karolinska Institutet, Stockholm, Sweden.|Admiraal de Ruyter Hospital, Goes, The Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: Leurs
authors.affiliation: Renal Medicine and Baxter Novum, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Anderstam
authors.affiliation: Renal Medicine and Baxter Novum, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Olof
authors.initials: O
authors.lastname: Heimburger
authors.affiliation: Renal Medicine and Baxter Novum, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Barany
authors.affiliation: Renal Medicine and Baxter Novum, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Stenvinkel
authors.affiliation: Renal Medicine and Baxter Novum, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Bengt
authors.initials: B
authors.lastname: Lindholm
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008137:Longitudinal Studies; D008239:Lysine / Q000031:analogs & derivatives* / Q000097:blood; D008297:Male; D008875:Middle Aged; D009752:Nutritional Status; D018384:Oxidative Stress; D012044:Regression Analysis; D051436:Renal Insufficiency, Chronic / Q000378:metabolism / Q000401:mortality* / Q000503:physiopathology*
chemical_list: D015415:Biomarkers; D001120:Arginine; C062187:pentosidine; D008239:Lysine