Elevated Plasma Concentrations of IL-6 and Elevated APACHE II Score Predict Acute Kidney Injury in Patients with Severe Sepsis

Abstract

Acute kidney injury (AKI) is common in critically ill patients with severe sepsis (SS), and the predictors of AKI in this population have not been well characterized. The study group was the placebo group of the Prospective Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) data set. PROWESS is a prospective, randomized, controlled study of the use of drotrecogin ␣ (activated) for the treatment of SS. Placebo patients who had an admission renal sepsis organ failure score of 2 or more were excluded. AKI was defined as an increase in serum creatinine of 25% or 0.3 mg/dl during the first week postbaseline. The incidence of relevant parameters was then compared in patients with and without AKI. Half of the patients were randomly assigned to a model-building data set, and multivariable Cox regression was used to determine risk factors. Factors that remained significant in the remaining "model validation" data set were considered significant. Of the 840 patients in the placebo group, 547 met inclusion criteria. Of the 547 patients, 127 (23.2%) patients met criteria for AKI. The mean age of the 547 patients was 59.8 ؎ 17.0, and 43.3% of the cohort were female. The ethnicity breakdown was as follows: White 83.2%, black 5.9%, and other 11%. Univariate analyses indicated that patients with AKI had a higher incidence of a dependence on the basis of activity of daily living scale (38.6 versus 26.7%; P ‫؍‬ 0.01), a lower baseline platelet count (193,000 versus 222,000; P ‫؍‬ 0.02), a higher baseline respiratory Sepsis Organ Failure Assessment score (2.9 versus 2.7; P ‫؍‬ 0.02), higher preinfusion Acute Physiology and Chronic Health Evaluation II (APACHE II) score (24.8 versus 22.0; P ‫؍‬ 0.0002), older age (63.7 versus 58.7 yr; P ‫؍‬ 0.008), and higher log IL-6 (6.6 versus 5.8; P ‫؍‬ 0.0006). In a multivariable Cox regression, the predictors of AKI were log IL-6 (P < 0.0001) and APACHE II (P ‫؍‬ 0.0008). Increased log IL-6 and APACHE II score are significant risk factors of AKI in patients with SS. IL-6 data and the absence of correlation with measures of hypotension (e.g., mean arterial pressure, dosage of vasopressors) support the notion that inflammation is a significant component of AKI in SS.

Can neutrophil–lymphocyte ratio be independent risk factor for predicting acute kidney injury in patients with severe sepsis?

“…Previously, two studies showed that APACHE II score aids to predict AKI in patients with sepsis. 30,35 As expected, APACHE II was a predictor of sepsis-related-AKI in our study. Because APACHE II score contains 12 routine physiological components, no single parameter of APACHE II could predict sepsis-related-AKI according to our results.…”

“…28,29 Clinical studies revealed that IL-6, procalcitonin (PCT) can be used as a predictive marker for sepsis-related-AKI in patients with sepsis. 30,31 In accordance with these studies, we showed that baseline NLR is fruitful and strong predictor of sepsis-related-AKI. Urine NGAL, L-type fatty acid-binding protein (L-FABP) is new and useful markers for early detection of AKI in critically ill adults with an eGFR over 60 mL/min per 1.73 m 2 .…”

Predictive and pathogenetic value of plasma biomarkers for acute kidney injury in patients with acute lung injury*

“…In the Norasept II study (29), there was a trend toward higher IL-6 levels in those subjects who subsequently developed acute kidney injury, but this result did not quite achieve statistical significance. More recently, in a secondary analysis of the PROWESS clinical trial of activated protein C for the treatment of severe sepsis, Chawla et al (32) demonstrated that baseline IL-6 levels were predictive for acute kidney injury. Our results are consistent with these findings and suggest that IL-6 is predictive in other critically ill patient populations, namely, those with acute lung injury.…”

Association between AKI and Long-Term Renal and Cardiovascular Outcomes in United States Veterans

“…Because patients who develop AKI and CKD also tend to have risk factors for cardiovascular disease (e.g., diabetes mellitus, hypertension, and hypercholesterolemia), some authors have suggested that the increased cardiovascular events and excess mortality outcomes seen in patients with kidney disease (both AKI and CKD) are largely an epiphenomenon due to shared risk factors (7,(17)(18)(19)(20)(21). AKI is associated with the development of CKD, and CKD is also a robust risk factor for major adverse cardiovascular events (MACE) (22).…”