Kidney Week

Abstract: FR-PO931

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

Session Information

• Glomerular Diseases: Potpourri
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Yu, Byung chul, Soonchunhyang University Hospital Bucheon, Bucheon, Gyeonggi-do, Korea (the Republic of)

Byung chul Yu, MD, PhD

• Choi, Soo Jeong, Soonchunhyang University Hospital Bucheon, Bucheon, Gyeonggi-do, Korea (the Republic of)

Soo Jeong Choi, MD, PhD

• Park, Moo Yong, Soonchunhyang University Hospital Bucheon, Bucheon, Gyeonggi-do, Korea (the Republic of)

Moo Yong Park, MD

• Kim, Jin kuk, Soonchunhyang University Hospital Bucheon, Bucheon, Gyeonggi-do, Korea (the Republic of)

Jin kuk Kim, PhD

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

We prospectively 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.