Use of Glomerular CD68+ Cells as a Surrogate Marker for Endocapillary Hypercellularity in Lupus Nephritis

Elisabeth M J Bos; Shirish R Sangle; Suzanne Wilhelmus; Ron Wolterbeek; Natasha Jordan; David D'Cruz; David Isenberg; H Terence Cook; Jan A Bruijn; Ingeborg M Bajema

doi:10.1016/j.ekir.2021.12.030

Use of Glomerular CD68+ Cells as a Surrogate Marker for Endocapillary Hypercellularity in Lupus Nephritis

Kidney Int Rep. 2022 Jan 11;7(4):841-847. doi: 10.1016/j.ekir.2021.12.030. eCollection 2022 Apr.

Authors

Affiliations

¹ Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
² Louise Coote Lupus Unit, Department of Rheumatology, Guy's Hospital, London, UK.
³ Pathan B.V., Laboratory for Pathology, Rotterdam, The Netherlands.
⁴ Department of Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands.
⁵ Department of Rheumatology, Addenbrooke's Hospital, Cambridge, UK.
⁶ Centre for Rheumatology, Division of Medicine, University College London, London, UK.
⁷ Centre for Inflammatory Diseases, Department of Immunology and Inflammation, Imperial College, London, UK.

Abstract

Introduction: Lupus nephritis (LN) class III or IV is strongly related to patient mortality and morbidity. The interobserver agreement of endocapillary hypercellularity by routine light microscopy, one of the most important lesions determining whether class III or IV is present, is moderate. In IgA nephropathy (IgAN), the presence of glomerular CD68+ cells was found to be a good surrogate marker for endocapillary hypercellularity. We investigated whether the presence of glomerular CD68+ cells could serve as a surrogate marker for endocapillary hypercellularity as well in LN.

Methods: A total of 92 LN biopsies were scored for the number of glomerular CD68+ cells using CD68 staining, including endocapillary hypercellularity and the activity index (AI). A new AI was calculated in which CD68+ cells replaced endocapillary hypercellularity. Clinical parameters were obtained from time of biopsy, 1 year after, and 2 years after.

Results: The number of glomerular CD68+ cells significantly correlated with endocapillary hypercellularity. A cutoff value of 7 for the maximum number of CD68+ cells within 1 glomerulus in a biopsy yielded a sensitivity of 88% and a specificity of 67% for the presence of endocapillary hypercellularity. Both endocapillary hypercellularity and CD68+ cells correlated with renal function during follow-up. The current and the new AI correlated equally well with the clinical outcome.

Conclusion: In LN, CD68+ cells can be used as a surrogate marker for endocapillary hypercellularity.

Keywords: activity index; endocapillary hypercellularity; glomerular CD68+ cells; lupus nephritis.