TY - JOUR
T1 - Association of T Cell–Derived Inflammatory Cytokines With Acute Kidney Injury and Mortality After Cardiac Surgery
AU - TRIBE-AKI Consortium
AU - Moledina, Dennis G.
AU - Mansour, Sherry G.
AU - Jia, Yaqi
AU - Obeid, Wassim
AU - Thiessen-Philbrook, Heather
AU - Koyner, Jay L.
AU - McArthur, Eric
AU - Garg, Amit X.
AU - Wilson, F. Perry
AU - Shlipak, Michael G.
AU - Coca, Steven G.
AU - Parikh, Chirag R.
N1 - Publisher Copyright:
© 2019 International Society of Nephrology
PY - 2019/12
Y1 - 2019/12
N2 - Introduction: Animal models of renal ischemia-reperfusion injury (IRI) demonstrate that interferon (IFN)-γ producing T-helper (Th)-1 cells worsen acute kidney injury (AKI), whereas interleukin (IL)-4– and IL-13–producing Th2 cells lead to repair. We tested the association of these cytokines with AKI and mortality in patients who underwent cardiac surgery. Methods: In 1444 participants of a multicenter, prospective, observational cohort, we measured 10 plasma biomarkers before and after cardiac surgery (IFN-γ, IL-4, IL-13, tumor necrosis factor [TNF]-α, IL-1β, IL-2, IL-6, IL-8, IL-10, and IL-12p70) and combined these biomarkers using principal component analysis (PCA). We also tested independent associations of Th1 (IFN-γ) and Th2 (IL-4 and IL-13) biomarkers with clinical outcomes of postoperative AKI and 1-year mortality. Results: AKI occurred in 492 participants (34%), and 1-year mortality occurred in 81 participants (6%). Within 6 hours after surgery, IFN-γ, IL-4, and IL-13 increased 2.1-, 6.0-, and 4.6-fold, respectively, from their preoperative levels. Patients with higher levels of IFN-γ had higher odds of AKI (adjusted odds ratio per log change, 1.35 [1.13, 1.6]) and mortality (1.51 [1.17, 1.94]). Patients with higher levels of IL-4 and IL-13 also had higher odds of AKI (1.26 [1.09, 1.46] and 1.4 [1.16, 1.69], respectively) and mortality (1.46 [1.18, 1.82] and 1.71 [1.27, 2.31], respectively). Adding biomarkers to the clinical variables through use of PCA improved the area under the curve by 0.01 for AKI and 0.04 for mortality, resulting in final areas under the curve of 0.85 (0.83–0.87) and 0.76 (0.70–0.81), respectively. Conclusion: Both Th1 and Th2 cytokines increased immediately after cardiac surgery and were associated with AKI and 1-year mortality. Our findings indicate activation of both Th1 and Th2 pathways after cardiac surgery rather than predominance of either pathway.
AB - Introduction: Animal models of renal ischemia-reperfusion injury (IRI) demonstrate that interferon (IFN)-γ producing T-helper (Th)-1 cells worsen acute kidney injury (AKI), whereas interleukin (IL)-4– and IL-13–producing Th2 cells lead to repair. We tested the association of these cytokines with AKI and mortality in patients who underwent cardiac surgery. Methods: In 1444 participants of a multicenter, prospective, observational cohort, we measured 10 plasma biomarkers before and after cardiac surgery (IFN-γ, IL-4, IL-13, tumor necrosis factor [TNF]-α, IL-1β, IL-2, IL-6, IL-8, IL-10, and IL-12p70) and combined these biomarkers using principal component analysis (PCA). We also tested independent associations of Th1 (IFN-γ) and Th2 (IL-4 and IL-13) biomarkers with clinical outcomes of postoperative AKI and 1-year mortality. Results: AKI occurred in 492 participants (34%), and 1-year mortality occurred in 81 participants (6%). Within 6 hours after surgery, IFN-γ, IL-4, and IL-13 increased 2.1-, 6.0-, and 4.6-fold, respectively, from their preoperative levels. Patients with higher levels of IFN-γ had higher odds of AKI (adjusted odds ratio per log change, 1.35 [1.13, 1.6]) and mortality (1.51 [1.17, 1.94]). Patients with higher levels of IL-4 and IL-13 also had higher odds of AKI (1.26 [1.09, 1.46] and 1.4 [1.16, 1.69], respectively) and mortality (1.46 [1.18, 1.82] and 1.71 [1.27, 2.31], respectively). Adding biomarkers to the clinical variables through use of PCA improved the area under the curve by 0.01 for AKI and 0.04 for mortality, resulting in final areas under the curve of 0.85 (0.83–0.87) and 0.76 (0.70–0.81), respectively. Conclusion: Both Th1 and Th2 cytokines increased immediately after cardiac surgery and were associated with AKI and 1-year mortality. Our findings indicate activation of both Th1 and Th2 pathways after cardiac surgery rather than predominance of either pathway.
KW - acute kidney injury
KW - cardiac surgery
KW - cardiopulmonary bypass
KW - inflammation
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U2 - 10.1016/j.ekir.2019.09.003
DO - 10.1016/j.ekir.2019.09.003
M3 - Article
C2 - 31844805
AN - SCOPUS:85074405002
SN - 2468-0249
VL - 4
SP - 1689
EP - 1697
JO - Kidney International Reports
JF - Kidney International Reports
IS - 12
ER -