title: Associations between Intensity of RRT, Inflammatory Mediators, and Outcomes.
abstract: OBJECTIVE
  Critically ill patients requiring RRT have higher circulating plasma concentrations of inflammatory and apoptosis markers that are associated with subsequent RRT dependence and death. Whether intensive dosing of RRT is associated with changes in specific mediators is unknown.
  
  
  METHODS
  A multicenter, prospective, cohort study of 817 critically ill patients receiving RRT ancillary to the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network study was conducted between November 2003 and July 2007. Plasma inflammatory (IL-6, IL-8, IL-10, IL-18, and macrophage migration inhibitory factor) and apoptosis (TNF receptor-I [TNFR-I], TNFR-II, and death receptor-5) biomarkers on days 1 and 8 were examined after initiation of intensive RRT. Whether intensive RRT, given day 1 biomarkers, is associated with RRT independence and lower mortality at day 60 was also examined.
  
  
  RESULTS
  Overall, no differences were found in day 8 biomarker concentrations between intensive and less-intensive RRT groups. When adjusted for day 1 biomarkers and clinical variables, intensive RRT was not associated with renal recovery (adjusted odds ratio [OR], 0.80; 95% confidence interval, 0.56 to 1.14) or mortality (adjusted OR, 1.15; 95% confidence interval, 0.81 to 1.64). Use of intensive RRT, however, was associated with lower day 8 concentrations when day 1 plasma IL-6, macrophage migration inhibitory factor, and TNFR-I concentrations were high (interaction P value for all markers, <0.01). In contrast, day 8 marker concentrations were higher when day 1 levels were low (P<0.01). Elevated biomarker concentrations on day 8 among 476 participants were associated with lower renal recovery (adjusted OR range, 0.19-0.87) and higher mortality (adjusted OR range, 1.26-3.18).
  
  
  CONCLUSIONS
  Among critically ill patients receiving RRT, intensive dosing of RRT has variable association with biomarker concentration and no association with renal recovery and mortality. However, elevated concentrations of inflammatory and apoptosis markers on day 8 of RRT were associated with RRT dependence and death.
authors: Center for Critical Care Nephrology and Clinical Research, Investigation, and Systems Modeling of Acute Illness Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania;
authors: Raghavan
authors: R
authors: Murugan
authors: Center for Critical Care Nephrology and Clinical Research, Investigation, and Systems Modeling of Acute Illness Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania;
authors: Xiaoyan
authors: X
authors: Wen
authors: Center for Critical Care Nephrology and Clinical Research, Investigation, and Systems Modeling of Acute Illness Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Department of Biostatistics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania;
authors: Christopher
authors: C
authors: Keener
authors: Center for Critical Care Nephrology and Clinical Research, Investigation, and Systems Modeling of Acute Illness Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Department of Biostatistics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania;
authors: Francis
authors: F
authors: Pike
authors: Center for Critical Care Nephrology and Clinical Research, Investigation, and Systems Modeling of Acute Illness Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Renal Section, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh; Pennsylvania;
authors: Paul M
authors: PM
authors: Palevsky
authors: Clinical Research, Investigation, and Systems Modeling of Acute Illness Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Division of Nephrology, Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico;
authors: Mark
authors: M
authors: Unruh
authors: Division of Renal Diseases and Hypertension, University of Texas Medical School at Houston, Texas; and.
authors: Kevin
authors: K
authors: Finkel
authors: Division of Renal Diseases, Washington University, St. Louis, Missouri.
authors: Anitha
authors: A
authors: Vijayan
authors: Center for Critical Care Nephrology and Clinical Research, Investigation, and Systems Modeling of Acute Illness Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania;
authors: Michele
authors: M
authors: Elder
authors: Clinical Research, Investigation, and Systems Modeling of Acute Illness Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Department of Biostatistics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania;
authors: Yi-Fan
authors: YF
authors: Chen
authors: Center for Critical Care Nephrology and Clinical Research, Investigation, and Systems Modeling of Acute Illness Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; kellumja@ccm.upmc.edu.
authors: John A
authors: JA
authors: Kellum
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D051017:Apoptosis Regulatory Proteins / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D016638:Critical Illness; D018836:Inflammation Mediators / Q000097:blood; D007668:Kidney / Q000503:physiopathology; D007674:Kidney Diseases / Q000097:blood / Q000175:diagnosis / Q000276:immunology / Q000401:mortality / Q000503:physiopathology / Q000628:therapy; D016015:Logistic Models; D016017:Odds Ratio; D011446:Prospective Studies; D020127:Recovery of Function; D017582:Renal Replacement Therapy / Q000009:adverse effects / Q000379:methods / Q000401:mortality; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D014493:United States Department of Veterans Affairs
chemical_list: D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; D018836:Inflammation Mediators
keywords: apoptosis; kidney disease; renal failure