Biomarker Enhanced Risk Prediction for Adverse Outcomes in Critically Ill Patients Receiving RRT

Abstract

Background and objectives Higher plasma concentrations of inflammatory and apoptosis markers in critically ill patients receiving RRT are associated with RRT dependence and death. This study objective was to examine whether plasma inflammatory ; macrophage migration inhibitory factor) and apoptosis (death receptor-5, tumor necrosis factor receptor I and II) biomarkers augment risk prediction of renal recovery and mortality compared with clinical models.Design, setting, participants, & measurements The Biologic Markers of Recovery for the Kidney study (n=817) was a prospective, nested, observational cohort study conducted as an ancillary to the Veterans Affairs/ National Institutes of Health Acute renal failure Trial Network study, a randomized trial of intensive versus less intensive RRT in critically ill patients with AKI conducted between November 2003 and July 2007 at 27 Veterans Affairs-and university-affiliated centers. Primary outcomes of interest were renal recovery and mortality at day 60. Conclusions This study suggests that a simple four-variable clinical model with plasma IL-8 had predictive value for renal recovery and mortality. These findings require external validation but could easily be used by clinicians.

Acute Kidney Injury: Tubular Markers and Risk for Chronic Kidney Disease and End-Stage Kidney Failure

“…A recent study by Bajwa et al [73] has also shown that bone marrow-derived dendritic cells deficient in sphingosine 1-phosphate receptor 3 can prevent ischemia-repufusion-induced AKI via a spleen-dependent mechanism and splenic T-regulatory cell expansion. These experimental results are in line with a recent clinical study showing inflammatory cytokine (IL-8), which augments the prediction of kidney recovery and mortality in AKI patients on renal replacement therapy [74] .…”

Biomarkers of acute kidney injury: the pathway from discovery to clinical adoption

“…Pike et al showed that combining plasma IL-8 with a 4-variable clinical model consisting of age, mean arterial blood pressure, mechanical ventilation, and bilirubin value enhanced the prediction of recovery of kidney function and death compared with the clinical model alone [169]. Likewise, the addition of a positive furosemide stress test to an elevation of NGAL > 150 ng/mL or [TIMP-2] × [IGFBP7] > 0.3 improved the predictive ability for AKI progression, need for RRT, and death compared with either biomarker alone [170].…”

Mechanisms and mediators of lung injury after acute kidney injury

“…These factors were requirement for mechanical ventilation, increasing age, increasing levels of bilirubin, and lower mean arterial pressure. 58 Thus, respiratory complications are a key marker of mortality risk in patients with AKI, suggesting a unique association between AKI and respiratory complications. This paradigm is especially true as the overall mortality of ALI is <20%, 59 whereas the overall mortality of AKI requiring RRT in the ATN trial was >60%.…”

“…SIRS is characterized by the early production and release of proinflammatory cytokines in response to sepsis, pancreatitis, and other systemic (indirect) causes of ALI. Data from patients with AKI indicate that AKI is also associated with a SIRS response and that serum levels of the proinflammatory cytokines IL-6, 47,75-78 IL-8, 47,58,75,78,79 and TNF 75 are increased. Studies suggest that proinflammatory cytokines can induce lung injury by directly injuring the lung endothelium and causing non-cardiogenic pulmonary oedema.…”

“…Patient data have demonstrated that AKI is associated with a proinflammatory phase and SIRS response as judged by increased serum IL-6, 47,75-78 IL-8, 47,58,75,78,79 and TNF 75 (Figure 3). 97 Conversely, patients with ESRD are generally considered immunosuppressed 98 and proinflammatory cytokine production might be dampened in these patients ( Figure 2).…”