RRT Intensity and Biomarkers in Critically Ill Patients

Clinical Journal of the American Society of Nephrology. 2015.10(6):926-933.

Circulating plasma concentrations of inflammatory and apoptosis markers associated with subsequent dependence on renal replacement therapy (RRT) and death are higher in critically ill patients requiring RRT. However, according to Raghavan Murugan, MD, and colleagues, there are few data on whether there is an association between intensive dosing of RRT and changes in specific mediators.

The researchers conducted a multicenter, prospective cohort study that included 817 critically ill patients receiving RRT ancillary to the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network study. Following initiation of RRT, the researchers examined plasma inflammatory (IL-6, IL-8, IL-10, IL-18, and macrophage migration inhibitory factor) and apoptosis (tumor necrosis factor receptor-I [TNFR-I], TNFR-II, and death receptor-5) biomarkers on days 1 and 8.

The researchers also sought to determine whether intensive RRT, given day 1, is associated with RRT independence and lower mortality at day 60.

The study found no differences in concentrations of day 8 biomarkers between intensive and less-intensive RRT groups. Following adjustment for day 1 biomarkers and clinical variables, there was no association between intensive RRT and renal recovery (adjusted odds ratio [OR], 0.80, 95% confidence interval [CI], 0.56-1.14) or mortality (adjusted OR, 1.15; 95% CI, 0.81-1.64).

There was an association with use of intensive RRT and 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 <.01). Conversely, day 8 marker concentrations were higher when day 1 levels were low (P<.01).

There was an association of elevated biomarker concentrations and lower renal recovery among 476 participants (adjusted OR, 0.19-0.87) and high mortality (adjusted OR range, 1.26-3.18).

“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,” the researchers said.