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Abstract: SA-PO652

More Severe Mitochondrial Injury at the Time of Diagnosis Is Associated With Poor Prognosis in IgA Nephropathy

Session Information

Category: Glomerular Diseases

  • 1302 Glomerular Diseases: Immunology and Inflammation

Authors

  • Yu, Byung chul, Soonchunhyang University Hospital Bucheon, Bucheon, Gyeonggi-do, Korea (the Republic of)
  • Lee, Kyung Ho, Soonchunhyang University Hospital Bucheon, Bucheon, Gyeonggi-do, Korea (the Republic of)
  • Choi, Soo Jeong, Soonchunhyang University Hospital Bucheon, Bucheon, Gyeonggi-do, Korea (the Republic of)
  • Park, Moo Yong, Soonchunhyang University Hospital Bucheon, Bucheon, Gyeonggi-do, Korea (the Republic of)
  • Kim, Jin kuk, Soonchunhyang University Hospital Bucheon, Bucheon, Gyeonggi-do, Korea (the Republic of)
Background

We hypothesized that the degree of mitochondrial injury at the time of diagnosis may serve as a valuable prognostic marker in IgA nephropathy (IgAN).

Methods

We prospectively enrolled 52 patients with IgAN. Focusing on the stimulator of interferon genes (STING)-NF-κB pathway activated by mitochondrial injury, the signal intensity of immunohistochemical (IHC) staining for STING and NF-κB was analyzed using kidney tissue at the time of diagnosis. Proteinuria at 6 months after treatment was categorized by conventional definitions of complete (<0.3 g/day) and partial remission (<3.5 g/day and 50% reduction in proteinuria). Time-averaged proteinuria (TA-proteinuria) was calculated as the average of the mean of proteinuria were obtained by 24-hour urine collection every 6 months for each patient.

Results

Kidney tissue from 40 patients showed positive IHC staining for STING and NF-κB. Patients were divided into the high (n = 21) and low (n = 31) intensity subgroups according to the signal intensity of IHC staining for STING and NF-κB based on 2+ and more or less, respectively. Fewer patients achieved complete or partial remission in the high intensity group than in the low intensity group (53.3 vs 94.1%, p = 0.013). During a median follow-up of 3.5 years, TA- proteinuria and mean annual rate of estimated glomerular filtration rate decline were higher in the high intensity group than in the low intensity group (0.99 ± 0.78 vs. 0.49 ± 0.32 g/day, p = 0.010; and -1.91 ± 4.71 vs. 1.55 ± 5.82 mL/min/1.73m2/year, p = 0.029, respectively).

Conclusion

More severe mitochondrial injury, as represented by a high signal intensity of IHC stain for STING and NF-κB at the time of diagnosis, could be used as a prognostic marker to predict poor prognosis in IgAN.

Immunohistochemical (IHC) staining of STING and NF-κB on kidney tissue obtained from patients. Patients were classified into 1+ (A), 2+ (B), and 3+ (C) according to the signal intensity of IHC staining.

Funding

  • Government Support – Non-U.S.