A – ARF quoted without specification
H- 04 : Inflammation
Associations between Intensity of RRT, Inflammatory Mediators, and
Outcomes
Raghavan Murugan*,†, Xiaoyan Wen*,†, Christopher Keener*,†,‡, Francis Pike*,†,‡,
Paul M.
Palevsky*,†,§, et al. on behalf of the Biological Markers of Recovery for the Kidney (BioMaRK) Study
Investigators - Author Affiliations
*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;
§Renal Section, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh; Pennsylvania;
¶Division of Nephrology, Department of Internal Medicine, University of New Mexico, Albuquerque,
New Mexico;
‖Division of Renal Diseases and Hypertension, University of Texas Medical School at Houston,
Texas; and
**Division of Renal Diseases, Washington University, St. Louis, Missouri
Correspondence : Dr. John A. Kellum, Critical Care Medicine, Translational Science, and
Bioengineering, The Center for Critical Care Nephrology, 608, Scaife Hall, 3550 Terrace Street,
Pittsburgh, PA 15261. Email: kellumja@ccm.upmc.edu
Journal : CJASN
Year : 2015 / Month : June
Volume : 10
Pages : 926-933
ABSTRACT
Background and objectives
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.
Design, setting, participants, & measurements
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 lessintensive 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.
COMMENTS
Critically ill patients requiring RRT are at a higher risk of RRT dependence and death .This increased
risk is not attenuated by intensive dosing of RRT compared with less-intensive RRT.
In this study, the authors :
- First examined whether intensive, compared with less-intensive RRT, is associated with lower
biomarker concentrations on day 8 relative to day 1.
- Second, they examined whether intensive RRT, given day 1 biomarker profile, is associated with
renal recovery and lower mortality at day 60.
- Third, they examined the association between day 8 biomarker concentration and outcomes.
- Finally, they examined subgroups of patients on the basis of their biomarker levels at enrollment
who would respond differently to the two RRT intensities.
Of participants receiving intensive RRT, intermittent hemodialysis was provided six times per week,
and continuous venovenous hemodiafiltration was prescribed to provide an effluent flow rate of 35
ml/kg body wt per hour. In the less-intensive strategy, intermittent hemodialysis was provided three
times per week, and continuous venovenous hemodiafiltration was prescribed to provide a total
effluent flow rate of 20 ml/kg body wt per hour. Cellulose triacetate or synthetic membranes were
used for all treatments, and the distribution of membranes was similar between the two RRT groups.
The primary outcomes were renal recovery and mortality at day 60. Renal recovery was defined as
being alive and independent from RRT by day 60.
Plasma IL-6, IL-8, IL-10, TNFR-I, TNFR-II, and DR-5 were assayed utilizing Life Technologies.
Invitrogen™ Luminex® assays (Grand Island NY, USA). Plasma MIF and IL-18 wereassayed utilizing
Bio-Rad Bio-Plex® Luminex® assays (Hercules CA, USA). All assays were measured on the Bio-Rad
Bio-Plex® 200 System with Bio-Plex Manager™ 4.0 software.
Among critically ill individuals requiring RRT, the use of intensive RRT was not associated with overall
lower plasma concentrations of inflammatory and apoptosis biomarkers on day 8 after initiation of
RRT. Intensive RRT was associated with lower mediator concentrations when baseline levels were
high. Although this interaction only reaches statistical significance for IL-6, MIF, and TNFR-I, it always
favors intensive RRT. However, despite this interaction, use of intensive RRT was not associated with
renal recovery or mortality given baseline marker profile., In contrast, elevated concentrations of
biomarkers on day 8 were associated with lower renal recovery and higher mortality.
The quest for robust markers of prognosis in AKI conditioning the appropriate dose of dialysis to be
delivered has not been conclusive so far.
Pr. Jacques CHANARD
Professor of Nephrology