Inflammation as a predictor of acute kidney injury and mediator of higher mortality after acute kidney injury in non-cardiac surgery

Abstract

This retrospective cohort study examined the roles of inflammation in acute kidney injury (AKI). Serum albumin and C-reactive protein (CRP) were used as markers of inflammation. Adults who underwent non-cardiac surgery from 2007 to 2011 were included. Exclusion criteria were urological surgery, obstetric surgery, missing data, and pre-operative dialysis. Subjects were followed until the end of 2015 or loss to follow-up. Associations between pre-operative albumin or CRP and post-operative AKI or association between AKI and mortality were examined by logistic or Cox regression, respectively. Mediation analyses were performed using albumin and CRP as mediators. Among 4,538 subjects, 272 developed AKI. Pre-operative albumin was independently associated with AKI (odds ratio [95% confidence interval (CI)]: 0.63 [0.48-0.83]). During a median follow-up of 4.5 years, 649 died. AKI was significantly associated with mortality (hazard ratio [HR] [95% CI]: 1.58 [1.22-2.04]). Further adjustment for pre-operative albumin and CRP attenuated the association (HR [95% CI]: 1.28 [0.99-1.67]). The proportions explained by mediating effects of lnCRP and albumin were 29.3% and 39.2% and mediation effects were statistically significant. In conclusion, inflammation is a predictor of AKI and a mediator of mortality after AKI. Interventions targeting inflammation might improve outcomes of AKI.

Figure 1

Flow of patients.

Figure 2

Kaplan-Meier curve for all-cause mortality among those with and without AKI. AKI: acute kidney injury.

Figure 3

Kaplan-Meier curves for all-cause mortality stratified by AKI status and serum albumin or CRP levels. “High” represents higher than median and “low” represents lower than or equal to median. (A) The light blue, red, green, and orange lines represent survival curves for those without AKI and low albumin, those without AKI and high albumin, those with AKI and low albumin, and those with AKI and high albumin, respectively. (B) The light blue, red, green, and orange lines represent survival curves for those without AKI and low CRP, those without AKI and high CRP, those with AKI and low CRP, and those with AKI and high CRP, respectively. AKI; acute kidney injury, CRP: C-reactive proteins.

Figure 4

Box plots of serum CRP and albumin levels among those with and without AKI. A box represents interquartile range and a horizontal line in the box shows the median value. A bar shows range and outliers are shown in circles. P values were by Man-Whitney U test comparing values for those with and without AKI at each time point. The number of patients with available values was shown in tables below the graphs. CRP: C-reactive protein, AKI: acute kidney injury.