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

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.