STING Pathway Activation Is Associated with Poor Prognosis in Acute Tubulointerstitial Nephritis

Background: We hypothesized that acute tubulointerstitial nephritis (ATIN) pathogenesis may be associated with mitochondrial injury and that the degree of mitochondrial injury at the time of diagnosis may serve as a valuable prognostic marker. Methods: Weprospectively enrolled 41 patients with ATIN. We analyzed the signal intensity of immunohistochemical (IHC) staining of the stimulator of interferon genes (STING) in kidney tissues at diagnosis as a proxy of mitochondrial injury in patients with ATIN. We evaluated clinical outcomes including achievement of complete remission (CR), defined as a doubling of estimated glomerular filtration rate (eGFR) compared with baseline values or eGFR≥ 60 mL/min/1.73m2 at 1 year after diagnosis. Results: A single pathologist categorized the signal intensity of the IHC staining from negative to 3+ (Figure 1). Patients were divided into the low- (n = 22) and high- (n = 19) intensity groups, with a cut-off of 2+. The mean baseline eGFR did not differ between low- and high-intensity group (24 ± 16 vs. 21 ± 14 mL/min/1.73m2, p = 0.541). The mean eGFR at 1 year after diagnosis were higher in the low- than in the high-intensity group (56 ± 25 vs. 39 ± 22 mL/min/1.73m2, p = 0.032). More patients achieved CR in the low- than in the high-intensity group (81.8 vs. 47.4%, p = 0.020). Low-intensity group was associated with CR (hazard ratio, 4.61; 95% confidence interval, 1.62 to 9.76, after adjustment for confounding factors including etiology, underlying pathological lesions, and presence of immunosuppressant administration). Conclusion: More severe mitochondrial injury, indicated by a high for STING IHC signal intensity at diagnosis, could be used as a prognostic marker to predict a poor prognosis in ATIN.Representative images of immunohistochemistric staining for STING on kidney tissue obtained from patients with acute tubulointerstitial nephritis. Patients were classified into negative (A), 1+ (B), 2+ (C), and 3+ (D) according to the IHC signal intensity.