Functional immune assay using interferon-gamma could predict infectious events in end-stage kidney disease

Background: Infections remain the second most common cause of death in patients with end-stage kidney disease (ESKD). We aimed to evaluate non-specific cell-mediated immunity in an ESKD cohort using a functional assay applicable to routine use, QuantiFERON-Monitor (Qiagen), and assess whether it can predict infectious events. Methods: In this prospective study, we performed the QuantiFERON-Monitor test in 80 subjects including 54 patients with ESKD. QuantiFERON-Monitor is based on the measurement of plasma interferon-gamma (IFN-gamma) after stimulation of NK-cells with a TLR-7 agonist, and T-cells with a TCR agonist. Patients were subsequently followed for 6 to 12 months. Results: QuantiFERON-Monitor showed lower stimulated IFN-gamma production in ESKD patients (n = 54) compared to healthy donors (n = 19) (p < 0.0001) and to chronic kidney disease stage 3-4 patients (n = 7) (hemodialysis (n = 30): p < 0.01; peritoneal dialysis (n = 13): p = 0.03 and ESKD on conservative management (n = 11): p < 0.001). No significant difference in stimulated IFN-gamma production was observed between ESKD patients with renal replacement therapies or conservative management. Stimulated IFN-gamma production was significantly lower in patients later developing infections (13.9 [5.5-48.3] IU/mL vs 85.8 [35.5-236) IU/mL, p = 0.007). Using ROC analysis, we identified a cutoff value of 63.55 IU/mL (sensitivity = 80.95%, specificity = 79.17%, AUC = 0.78, p = 0.008) to discriminate patients at higher risk of infections. Patients with stimulated IFN-gamma levels measured by QuantiFERON Monitor below 63.55 IU/mL (n = 21) had a hazard ratio of 10.71 ([3.68-31.13], p < 0.0001) for the development of subsequent infections. Conclusion: Monitoring of IFN-gamma production after stimulation of innate and adaptive immunity may identify ESKD patients with high risk of infection. This allows for therapeutic interventions to restore cellular immunity, thereby minimizing both infections and rejections after kidney-transplantation.