Clinical Trajectories of Acute Kidney Injury in Surgical Sepsis: A Prospective Observational Study

Abstract

Objective: To characterize endothelial function, inflammation, and immunosuppression in surgical patients with distinct clinical trajectories of AKI and to determine the impact of persistent kidney injury and renal non-recovery on clinical outcomes, resource utilization, and long-term disability and survival.

Summary of background data: AKI is associated with increased healthcare costs and mortality. Trajectories that account for duration and recovery of AKI have not been described for sepsis patients, who are uniquely vulnerable to renal dysfunction.

Methods: This prospective observational study included 239 sepsis patients admitted and enrolled between January 2015 and July 2017. Kidney Disease: Improving Global Outcomes (KDIGO) and Acute Disease Quality Initiative (ADQI) criteria were used to classify subjects as having no AKI, rapidly reversed AKI, persistent AKI with renal recovery, or persistent AKI without renal recovery. Serial biomarker profiles, clinical outcomes, resource utilization, and long-term physical performance status and survival were compared among AKI trajectories.

Results: Sixty-two percent of the study population developed AKI. Only one-third of AKI episodes rapidly reversed within 48 hours; the remaining had persistent AKI, among which 57% did not have renal recovery by discharge. One-year survival and proportion of subjects fully active 1 year after sepsis was lowest among patients with persistent AKI compared with other groups. Long-term mortality hazard rates were 5-fold higher for persistent AKI without renal recovery compared with no AKI.

Conclusions: Among critically ill surgical sepsis patients, persistent AKI and the absence of renal recovery are associated with distinct early and sustained immunologic and endothelial biomarker signatures and decreased long-term physical function and survival.

Figure 1.

A. Trajectories of acute kidney injury in sepsis ^a Significantly different from No AKI group (Bonferroni-adjusted p<0.05) ^b Significantly different from rapidly reversed AKI group (Bonferroni-adjusted p<0.05) ^c Significantly different from persistent AKI with recovery (Bonferroni-adjusted p<0.05) B. Adjusted Kaplan-Meier survival curves and number at risk by AKI trajectories Propensity score based inverse weighting was used to plot adjusted Kaplan Meier curves where propensity of being in a trajectory group was calculated using multinomial logistic model that included patient demographics (age, gender, ethnicity), Charlson comorbidity score, septic shock and non-renal SOFA score on sepsis onset. C. Hazard ratios for all-cause mortality by AKI trajectories * p<0.05 for Bonferroni-adjusted log-rank test when compared to all other groups ^d Adjusted for age, gender, ethnicity, Charlson comorbidity score, sepsis shock status and non-renal SOFA score on sepsis onset, and total ICU length of stay. Abbreviations. RRT, renal replacement therapy; GFR, glomerular filtration rate ; MAKE-365, major adverse kidney events composite outcome of death, renal replacement therapy dependence, or having an estimated GFR less than 60 ml/min/1.72m² at one year of sepsis onset. Hospital outcomes were reported among patients who were not withdrawn from the study at the time of hospital discharge and one year outcomes were reported among hospital survivors were not withdrawn from the study and had renal data available at one year.

Figure 2.

Kinetic glomerular filtration rate, cumulative net fluid balance, and immune and endothelial biomarker trajectories by AKI trajectory groups A. Kinetic glomerular filtration rate B. Cumulative net fluid balance as a percentage of admission weight C. Tumor necrosis factor (TNF-alpha) D. Interleukin 6 (IL-6) E. Monocyte chemoattractant protein 1 (MCP1) F. Interferon gamma-induced protein 10 (IP-10) G. Interleukin 8 (IL-8) H. Soluble programmed death-ligand 1 (sPDL-1) I. Total lymphocyte count J. Angiopoietin 2 (ANG-2) K. Soluble vascular endothelial growth factor receptor-1 (sFLT-1) L. Vascular Endothelial Growth Factor (VEGF) Gray lines represent median values for healthy controls provided by manufacturer of the ELISA and Luminex multiplex kits used as detailed in Supplemental Methods.