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 - Funding Information:
The National Institutes of Health (NIH; RO1HL085757 ) funded the TRIBE-AKI Consortium. NIH grants supported CRP (K24DK090203), SGC (R01DK096549), FPW (K23DK097201, R01DK113191), and DGM (K23DK117065). SGC, AXG, and CRP are members of the ASSESS-AKI Consortium (U01DK082185). CRP, FPW, and DGM are supported by the Yale O’Brien Center Grant (P30-DK-079310). The Institute for Clinical Evaluative Sciences (ICES), which is funded by Ontario Ministry of Health and Long-Term Care (MOHLTC), supported this study. SGM is supported by the Robert E. Leet and Clara Guthrie Patterson Trust and the American Heart Association. The opinions, results and conclusions reported in this paper are those of the authors and are independent from the funding sources. No endorsement by NIH, ICES, or the Ontario MOHLTC is intended or should be inferred.
Funding Information:
The National Institutes of Health (NIH; RO1HL085757) funded the TRIBE-AKI Consortium. NIH grants supported CRP (K24DK090203), SGC (R01DK096549), FPW (K23DK097201, R01DK113191), and DGM (K23DK117065). SGC, AXG, and CRP are members of the ASSESS-AKI Consortium (U01DK082185). CRP, FPW, and DGM are supported by the Yale O'Brien Center Grant (P30-DK-079310). The Institute for Clinical Evaluative Sciences (ICES), which is funded by Ontario Ministry of Health and Long-Term Care (MOHLTC), supported this study. SGM is supported by the Robert E. Leet and Clara Guthrie Patterson Trust and the American Heart Association. The opinions, results and conclusions reported in this paper are those of the authors and are independent from the funding sources. No endorsement by NIH, ICES, or the Ontario MOHLTC is intended or should be inferred. This study was presented at the American Society of Nephrology meeting at New Orleans, Louisiana, in October 31, 2017 to November 5, 2017.
Funding Information:
JLK has received research fees from Bioporto and Astute Medical and consulting fees from Baxter, Astute Medical, and Sphingotec. MGS received grant support from Cricket Health, Inc. and consultancy fees from the University of Washington and has equity in TAI diagnostics and Cricket Health, Inc. SGC and CRP are on the Advisory Board of RenalytixAI and both own equity in this company. SGC received consulting fees from Goldfinch Bio, CHF Solutions, Quark Biopharma, Janssen Pharmaceuticals, and Takeda Pharmaceuticals. CRP is on the Data Safety and Monitoring Board of Genfit. All the other authors declared no competing interests.
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
UR - http://www.scopus.com/inward/record.url?scp=85074405002&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85074405002&partnerID=8YFLogxK
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 -