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. 2025 Nov 20;11(2):103686.
doi: 10.1016/j.ekir.2025.11.011. eCollection 2026 Feb.

Characterizing the NIH Activity and Chronicity Indices in 2 Independent Lupus Nephritis Cohorts

Valentina Querin  1   2 , Natasha Jordan  3   4 , David P D'Cruz  5 , David Isenberg  6 , Suzanne Wilhelmus  7 , Helmut Schumacher  8 , H Terence Cook  9 , Augusto Vaglio  2   10 , Ingeborg M Bajema  1
Affiliations

Characterizing the NIH Activity and Chronicity Indices in 2 Independent Lupus Nephritis Cohorts

Valentina Querin et al. Kidney Int Rep. .

Abstract

Introduction: The inclusion of National Institutes of Health (NIH) activity index (AI) and chronicity index (CI) in the ISN/Renal Pathology Society (ISN/RPS) classification of lupus nephritis (LN) aims to provide a precise characterization of the amount of active and chronic lesions next to lupus class. We here investigate the distribution of NIH indices within 2 international LN cohorts, their relationship with the ISN/RPS classes and which lesions most significantly contribute to these scores.

Methods: We collected 194 biopsies from 2 cohorts of patients with LN and calculated the NIH AI and CI according to the revised 2018 ISN/RPS classification. For statistical analysis we mainly used nonparametric tests. An exploratory factor analysis was applied to the lesion scores.

Results: The NIH AI score was usually medium-low, reaching a maximum value of 16 of 24, whereas the NIH CI reached 10 of 12. Both indices were higher in classes III, IV, and mixed compared with others (P < 0.0001). Endocapillary hypercellularity was present in > 70% of biopsies, showing a strong correlation with neutrophils/karyorrhexis (r = 0.78, P < 0.0001) and cellular crescents (P < 0.0001). Chronic lesions showed a strong correlation with each other (P < 0.0001), except for fibrous crescents which had the strongest correlation with cellular crescents (r = 0.33, P < 0.0001). The inclusion of all lesions in an exploratory factor analysis uncovered 2 underlying main factors that accurately reflect the NIH AI and CI.

Conclusion: This study revealed key aspects of the NIH AI and CI that may guide future modifications of these indices, leading to a more balanced and reliable scoring system.

Keywords: activity index; chronicity index; histopathological classification; lupus nephritis.

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Figures

None
Graphical abstract
Figure 1
Figure 1
On the left, the 6 lesions included in the NIH AI (0-24) are shown: (a) Endocapillary hypercellularity (0-3), (b) Neutrophils/karyorrhexis (0-3), (c) Fibrinoid necrosis (0-3)x2, (d) Hyaline deposits (0-3), (e) Cellular/fibrocellular crescents (0-3)x2, (f) Interstitial inflammation (0-3). On the right, the 4 lesions included in the NIH CI are shown (0-12): (g) Global glomerulosclerosis (0-3), (h) Interstitial fibrosis (0-3), I. Tubular atrophy (0-3), L. Fibrous crescents (0-3). NIH AI, National Institutes of Health activity index; NIH CI, National Institutes of Health chronicity index.
Figure 2
Figure 2
Distribution of the NIH AI score in cohort 1 (above) and cohort 2 (below). NIH AI, National Institutes of Health activity index.
Figure 3
Figure 3
Distribution of the NIH CI score in cohort 1 (above) and cohort 2 (below). NIH CI, National Institutes of Health chronicity index.
Figure 4
Figure 4
Score distribution of the active and chronic lesions in the 194 kidney biopsies. Cel_cre, cellular/fibrocellular crescents; End_hyp, endocapillary hypercellularity; Fib_cre, fibrous crescents; Fib_nec, fibrinoid necrosis; Hya_dep, hyaline deposits; Int_fib, interstitial fibrosis; Int_inf, interstitial inflammation; Neu_kar, neutrophils/karyorrhexis; Tot_scl, total glomerulosclerosis score; Tub_atr, tubular atrophy.
See this image and copyright information in PMC

References

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