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Use of Glomerular CD68+ Cells as a Surrogate Marker for Endocapillary Hypercellularity in Lupus Nephritis
Elisabeth M J Bos1, Shirish R Sangle2, Suzanne Wilhelmus1,3
1Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Insights
Glomerular CD68+ cells can serve as a reliable surrogate marker for endocapillary hypercellularity in lupus nephritis (LN). This finding improves the assessment of LN class III/IV, aiding in predicting patient outcomes.
Area of Science:
- Nephrology
- Immunopathology
- Renal Pathology
Background:
- Lupus nephritis (LN) classes III and IV are associated with significant patient morbidity and mortality.
- Endocapillary hypercellularity is a key diagnostic feature for LN classes III/IV but exhibits moderate interobserver agreement.
- Glomerular CD68+ cells have shown promise as a surrogate marker for endocapillary hypercellularity in IgA nephropathy.
Purpose of the Study:
- To investigate the utility of glomerular CD68+ cells as a surrogate marker for endocapillary hypercellularity in lupus nephritis (LN).
- To assess the correlation between CD68+ cell counts and established markers of LN activity and clinical outcomes.
Main Methods:
- Analyzed 92 LN kidney biopsies using CD68 staining to quantify glomerular CD68+ cells.
- Assessed endocapillary hypercellularity and calculated the activity index (AI), including a modified AI replacing endocapillary hypercellularity with CD68+ cells.
- Correlated CD68+ cell counts and AI with clinical parameters at baseline, 1 year, and 2 years post-biopsy.
Main Results:
- A significant positive correlation was observed between the number of glomerular CD68+ cells and endocapillary hypercellularity.
- A cutoff of 7 CD68+ cells per glomerulus demonstrated 88% sensitivity and 67% specificity for detecting endocapillary hypercellularity.
- Both endocapillary hypercellularity and CD68+ cell counts correlated with renal function and clinical outcomes, with the modified AI showing comparable predictive value to the standard AI.
Conclusions:
- Glomerular CD68+ cells are a valid surrogate marker for endocapillary hypercellularity in lupus nephritis.
- Utilizing CD68+ cells can potentially improve the diagnostic accuracy and prognostic assessment of LN.
- This approach may enhance the evaluation of LN activity and patient prognosis.
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.
