J Rheum Dis.  2022 Oct;29(4):232-242. 10.4078/jrd.22.0011.

Interstitial Inflammation in the ISN/RPS 2018 Classification of Lupus Nephritis Predicts Renal Outcomes and is Associated With Bcl-2 Expression

• Lee SJ
• Nam EJ
• Han MH
• Kim YJ

• KMID: 2533624
• DOI: http://doi.org/10.4078/jrd.22.0011

Abstract

Objective
To investigate the histopathological characteristics of patients with lupus nephritis in the 2018 revised International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification and assess the prognostic factors.
Methods
This study enrolled 92 patients with lupus nephritis, who had conventional treatment and renal biopsy. Each renal tissue was evaluated according to 2018 ISN/RPS classification, and quantified apoptotic regulator protein, the B-cell lymphoma-2 protein (Bcl-2), expressions in selected lymphocyte subsets were measured using novel computational approaches using multicolor confocal images. Histopathological characteristics and prognostic factors of end-stage renal disease (ESRD) and chronic kidney disease (CKD) were compared. Follow-up data were obtained, and survival analysis was conducted.
Results
During follow-up period (average: 74.3 months), 16 and 18 patients progressed ESRD and CKD, respectively. Multivariable analysis of age, sex, disease activity and pathological features in ISN/RPS demonstrated the extent of interstitial inflammation (grade 0~3) was significantly associated with both ESRD and CKD. When interstitial inflammation was divided into mild (grade 0, 1) and severe (grade 2, 3), Cox regression analysis showed that patients with severe interstitial inflammation were significantly increased risk of both ESRD and CKD (hazard ratio: 4.67 and 3.8, respectively). Bcl-2 expression in CD4+ and CD20 cells was significantly higher in the severe interstitial inflammation group compared to in mild interstitial inflammation patients (p=0.006 and 0.010, respectively).
Conclusion
The extent of interstitial inflammation can predict clinical renal outcomes. Significantly elevated Bcl-2 expression in both CD4+ and CD20 cells was found in severe interstitial inflammation compared with mild interstitial inflammation.

Keyword

Lupus nephritis; Inflammation; Prognosis

Figure

• 

  Fig. 1 Prediction of renal survival by interstitial inflammation severity. Kaplan–Meier curves are described according to the interstitial inflammation (A, C) in ISN/RPS classification and mild (grades 0 and 1) versus severe (grades 2 and 3) interstitial inflammation (B, D). Kaplan–Meier survival curves with ESRD (A, B) and CKD (C, D) in patients with lupus nephritis. ISN/RPS: International Society of Nephrology/Renal Pathology Society, ESRD: end-stage renal disease, CKD: chronic kidney disease.

• 

  Fig. 2 B-cell lymphoma-2 (Bcl-2) expression in patients with lupus nephritis by interstitial inflammation severity. The frequency of Bcl-2 expression was calculated on interstitium in renal tissues from 28 enrolled patients with mild (n=20) versus severe (n=8) interstitial inflammation. Total cells (A), frequency of Bcl-2 (B), CD4+ cells (C), CD20+ cells (D), Bcl-2 expressing CD4+ cells (E), and Bcl-2 expressing CD20+ cells (F) were compared between patients with mild and severe interstitial inflammation of renal samples. Mild=score (0~1); severe=scores (2~3) in activity index of interstitial inflammation. *p<0.05; **p<0.01.

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