title: The role of laser Doppler flowmetry tests, serum angiopoietin-2, asymmetric and symmetric dimethylarginine to predict outcome in chronic kidney disease.
abstract: The role of biochemical and functional markers of microvascular dysfunction to predict cardiovascular outcomes in nondialyzed chronic kidney disease (CKD) remains unclear. In this prospective cohort study, we assessed whether biochemical [serum level of angiopoietin-2 (Ang-2), asymmetric and symmetric dimethylarginin] and functional (laser Doppler flowmetry) measures of microvascular function predicted cardiovascular events, cardiovascular and all-cause mortality in CKD patients.
  
  
  
  Postocclusive reactive hyperemia area (PORHHA), acetylcholine and sodium nitroprusside-mediated flow changes were estimated by laser Doppler flowmetry, and Ang-2, asymmetric and symmetric dimethylarginin were assessed in 105 CKD patients at baseline. Multiple failure time Cox-regression analyses with backward elimination were performed to determine the predictors of the combined endpoint of cardiovascular mortality and cardiovascular events or all-cause mortality and cardiovascular events during a median of 66.6 (interquartile range 39.8-80.4) months of follow-up.
  
  
  
  In univariate models lnAng-2 and lnPORHHA both predicted the cardiovascular outcome besides age, diabetes, baseline cardiovascular disease, brachial pulse pressure and log C-reactive protein. In multivariate analysis lnPORHHA [hazard ratio: 0.66 (95% confidence interval: 0.49-0.89) per ln(mU s)], age [1.03 (1.01-1.06) per year], log C-reactive protein [1.31 (1.06-1.64) per ln(mg/l)] and diabetes [3.33 (1.70-6.53)] remained significant predictors of the cardiovascular outcome, whereas lnAng-2 did not enter the model. Neither of the microvascular variables were an independent predictor of all-cause mortality and cardiovascular events.
  
  
  
  Among the functional and biochemical microvascular parameters PORHHA seems to improve cardiovascular risk assessment in CKD. Nevertheless the robustness of traditional risk factors seems to outweigh the role of microvascular biomarkers on all-cause mortality and cardiovascular events at this time.
authors.affiliation: aDepartment of Family Medicine, Semmelweis University bHealth Service of Zugló (ZESZ) cDepartment of Transplantation and Surgery, Semmelweis University, Budapest, Hungary dDepartment of Internal Medicine II, University Hospital Regensburg, Regensburg eDivision of Nephrology and Hypertension, Department of Medicine, Hannover Medical School, Hannover fDivision of General Internal Medicine, Nephrology, and Rheumatology, Department of Medicine D, University Hospital Münster, Münster, Germany g1st Department of Medicine, Semmelweis University hNephrology Division, Uzsoki Teaching Hospital iDepartment of Cardiology, St. Imre Teaching Hospital jDivision of Angiology, Department of Medicine, St. Imre Teaching Hospital kB Braun Avitum Nephrological Network lDivision of Nephrology, Department of Medicine, St. Imre Teaching Hospital, Budapest, Hungary.
authors.forename: János
authors.initials: J
authors.lastname: Nemcsik
authors.forename: Orsolya
authors.initials: O
authors.lastname: Cseprekál
authors.forename: József
authors.initials: J
authors.lastname: Egresits
authors.forename: Jan
authors.initials: J
authors.lastname: Kielstein
authors.forename: Philipp
authors.initials: P
authors.lastname: Kümpers
authors.forename: Alexander
authors.initials: A
authors.lastname: Lukasz
authors.forename: Ádám
authors.initials: Á
authors.lastname: Tabák
authors.forename: Adrienn
authors.initials: A
authors.lastname: Marton
authors.forename: Zsófia K
authors.initials: ZK
authors.lastname: Németh
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Járai
authors.forename: Gabriella
authors.initials: G
authors.lastname: Godina
authors.forename: László
authors.initials: L
authors.lastname: Sallai
authors.forename: Katalin
authors.initials: K
authors.lastname: Farkas
authors.forename: István
authors.initials: I
authors.lastname: Kiss
authors.forename: András
authors.initials: A
authors.lastname: Tislér
mesh_terms: D000367:Age Factors; D000368:Aged; D042702:Angiopoietin-2 / Q000097:blood*; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000401:mortality*; D003920:Diabetes Mellitus / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006940:Hyperemia / Q000000981:diagnostic imaging*; D017078:Laser-Doppler Flowmetry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012079:Renal Circulation; D051436:Renal Insufficiency, Chronic / Q000503:physiopathology*; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D042702:Angiopoietin-2; D015415:Biomarkers; C024917:symmetric dimethylarginine; D002097:C-Reactive Protein; D001120:Arginine