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

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.

Graphical abstract

Figure 1

CD68-positive cells in lupus nephritis in relation to histologic findings. (a) LN class IV, glomerulus with abundance of CD68-positive cells. (b) Same glomerulus as found in a; CD68-positive cells are present in areas with endocapillary hypercellularity (big arrows in a and b) but also in extracapillary proliferation (small arrows in a and b). (c) Absence of glomerular CD68-positive cells whereas a small lesion with endocapillary hypercellularity (arrow) is present (d) revealing sampling error may give rise to inconsistent results. (e) Virtual absence of CD68-positive cells in a glomerulus with many wire loops, consistent with class IV but in the absence of endocapillary hypercellularity.

Figure 2

E continuous and CD68 continuous. ρ = 0.784; P < 0.001. The fraction of glomeruli with endocapillary hypercellularity and ≥7 CD68+ cells in a biopsy, each dot represents a biopsy.

Figure 3

E continuous and CD68 continuous per class. The fraction of glomeruli with endocapillary hypercellularity and ≥7 CD68+ cells in a biopsy compared between classes. Bars represent the median of the group, whiskers the interquartile range. ∗∗∗P ≤ 0.001; ∗∗∗∗P ≤ 0.0001.