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

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Introduction The inclusion of National Institutes of Health (NIH) activity (AI) and chronicity (CI) indices in the International Society of Nephrology/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 two 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 two 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 non-parametric 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 16/24, while the NIH CI reached 10/12. Both indices were higher in classes III, IV and mixed compared to others (p<.0001). Endocapillary hypercellularity was present in more than 70% biopsies, showing a strong correlation with neutrophils/karyorrhexis (r=0.78, p<.0001) and cellular crescents (p<.0001). Chronic lesions showed a strong correlation with each other (p<.0001), except for fibrous crescents which had the strongest correlation with cellular crescents (r=0.33, p<.0001). The inclusion of all lesions in an exploratory factor analysis uncovered two 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.

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