Serum IL-17 levels are higher in critically ill patients with AKI and associated with worse outcomes

BACKGROUND: Interleukin-17 (IL-17) antagonism in rats reduces the severity and progression of AKI. IL-17-producing circulating T helper-17 (TH17) cells is increased in critically ill patients with AKI indicating that this pathway is also activated in humans. We aim to compare serum IL-17A levels in critically ill patients with versus without AKI and to examine their relationship with mortality and major adverse kidney events (MAKE). METHODS: Multicenter, prospective study of ICU patients with AKI stage 2 or 3 and without AKI. Samples were collected at 24-48 h after AKI diagnosis or ICU admission (in those without AKI) timepoint 1, T1 and 5-7 days later timepoint 2, T2. MAKE was defined as the composite of death, dependence on kidney replacement therapy or a reduction in eGFR of ≥ 30% from baseline up to 90 days following hospital discharge. RESULTS: A total of 299 patients were evaluated. Patients in the highest IL-17A tertile (versus lower tertiles) at T1 had higher acuity of illness and comorbidity scores. Patients with AKI had higher levels of IL-17A than those without AKI: T1 1918.6 fg/ml (692.0-5860.9) versus 623.1 fg/ml (331.7-1503.4), p < 0.001; T2 2167.7 fg/ml (839.9-4618.9) versus 1193.5 fg/ml (523.8-2198.7), p = 0.006. Every onefold higher serum IL-17A at T1 was independently associated with increased risk of hospital mortality (aOR 1.35, 95% CI: 1.06-1.73) and MAKE (aOR 1.26, 95% CI: 1.02-1.55). The highest tertile of IL-17A (vs. the lowest tertile) was also independently associated with higher risk of MAKE (aOR 3.03, 95% CI: 1.34-6.87). There was no effect modification of these associations by AKI status. IL-17A levels remained significantly elevated at T2 in patients that died or developed MAKE. CONCLUSIONS: Serum IL-17A levels measured by the time of AKI diagnosis or ICU admission were differentially elevated in critically ill patients with AKI when compared to those without AKI and were independently associated with hospital mortality and MAKE.