Relationship between renal CD68+ infiltrates and the Oxford Classification of IgA nephropathy
Aims: The Oxford Classification E score (endocapillary hypercellularity) predicts renal functional decline in IgA nephropathy (IgAN) patients free from steroid/immunosuppressive (IS) therapy, but is poorly reproducible. We hypothesise that endocapillary hypercellularity reflects glomerular inflammat...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Journal Article |
| Published: |
2019
|
| Online Access: | http://hdl.handle.net/20.500.11937/73948 |
| _version_ | 1848763140060217344 |
|---|---|
| author | Soares, M. Genitsch, V. Chakera, Aron Smith, A. MacEwen, C. Bellur, S. Alham, N. Roberts, I. |
| author_facet | Soares, M. Genitsch, V. Chakera, Aron Smith, A. MacEwen, C. Bellur, S. Alham, N. Roberts, I. |
| author_sort | Soares, M. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Aims: The Oxford Classification E score (endocapillary hypercellularity) predicts renal functional decline in IgA nephropathy (IgAN) patients free from steroid/immunosuppressive (IS) therapy, but is poorly reproducible. We hypothesise that endocapillary hypercellularity reflects glomerular inflammation and that the presence of CD68-positive cells is a more robust marker of E score. Methods and results: CD68-positive cells were quantified in glomeruli and tubulointerstitium in biopsies from 118 IgAN patients, and cell counts were correlated with the criteria of the Oxford Classification, assigned on PAS-stained serial sections. There was a strong correlation between median glomerular CD68 count and the percentage of glomeruli showing endocapillary hypercellularity (r = 0.67; P < 0.001; r2 = 0.45), while there was no correlation between CD68-positive cells and mesangial hypercellularity, % segmental sclerosis, % of crescents and % tubular atrophy/interstitial fibrosis (TA/IF). ROC curve analysis demonstrated that a maximum glomerular CD68 count of 6 is the best cut-off for distinguishing E0 from E1 (sensitivity 94.1%, specificity 71%, area under the curve = 89%). Identification of biopsies with a maximum glomerular CD68-count >6 was reproducible (kappa score 0.8), and there was a strong correlation between glomerular CD68 counts obtained by conventional light microscopy and by image analysis (r = 0.80, r2 = 0.64, P < 0.0001). Digital image analysis revealed that tubulointerstitial CD68-positive cells correlated moderately with % TA/IF (r = 0.59, r2 = 0.35, P < 0.001) and GFR at the time of biopsy (r = 0.54, r2 = 0.29, P < 0.0001), but not with mesangial and endocapillary hypercellularity. Conclusions: While glomerular CD68-positive cells emerge as markers of endocapillary hypercellularity, their tubulointerstitial counterparts are associated with chronic damage. |
| first_indexed | 2025-11-14T10:58:43Z |
| format | Journal Article |
| id | curtin-20.500.11937-73948 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T10:58:43Z |
| publishDate | 2019 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-739482019-07-12T06:29:03Z Relationship between renal CD68+ infiltrates and the Oxford Classification of IgA nephropathy Soares, M. Genitsch, V. Chakera, Aron Smith, A. MacEwen, C. Bellur, S. Alham, N. Roberts, I. Aims: The Oxford Classification E score (endocapillary hypercellularity) predicts renal functional decline in IgA nephropathy (IgAN) patients free from steroid/immunosuppressive (IS) therapy, but is poorly reproducible. We hypothesise that endocapillary hypercellularity reflects glomerular inflammation and that the presence of CD68-positive cells is a more robust marker of E score. Methods and results: CD68-positive cells were quantified in glomeruli and tubulointerstitium in biopsies from 118 IgAN patients, and cell counts were correlated with the criteria of the Oxford Classification, assigned on PAS-stained serial sections. There was a strong correlation between median glomerular CD68 count and the percentage of glomeruli showing endocapillary hypercellularity (r = 0.67; P < 0.001; r2 = 0.45), while there was no correlation between CD68-positive cells and mesangial hypercellularity, % segmental sclerosis, % of crescents and % tubular atrophy/interstitial fibrosis (TA/IF). ROC curve analysis demonstrated that a maximum glomerular CD68 count of 6 is the best cut-off for distinguishing E0 from E1 (sensitivity 94.1%, specificity 71%, area under the curve = 89%). Identification of biopsies with a maximum glomerular CD68-count >6 was reproducible (kappa score 0.8), and there was a strong correlation between glomerular CD68 counts obtained by conventional light microscopy and by image analysis (r = 0.80, r2 = 0.64, P < 0.0001). Digital image analysis revealed that tubulointerstitial CD68-positive cells correlated moderately with % TA/IF (r = 0.59, r2 = 0.35, P < 0.001) and GFR at the time of biopsy (r = 0.54, r2 = 0.29, P < 0.0001), but not with mesangial and endocapillary hypercellularity. Conclusions: While glomerular CD68-positive cells emerge as markers of endocapillary hypercellularity, their tubulointerstitial counterparts are associated with chronic damage. 2019 Journal Article http://hdl.handle.net/20.500.11937/73948 10.1111/his.13768 restricted |
| spellingShingle | Soares, M. Genitsch, V. Chakera, Aron Smith, A. MacEwen, C. Bellur, S. Alham, N. Roberts, I. Relationship between renal CD68+ infiltrates and the Oxford Classification of IgA nephropathy |
| title | Relationship between renal CD68+ infiltrates and the Oxford Classification of IgA nephropathy |
| title_full | Relationship between renal CD68+ infiltrates and the Oxford Classification of IgA nephropathy |
| title_fullStr | Relationship between renal CD68+ infiltrates and the Oxford Classification of IgA nephropathy |
| title_full_unstemmed | Relationship between renal CD68+ infiltrates and the Oxford Classification of IgA nephropathy |
| title_short | Relationship between renal CD68+ infiltrates and the Oxford Classification of IgA nephropathy |
| title_sort | relationship between renal cd68+ infiltrates and the oxford classification of iga nephropathy |
| url | http://hdl.handle.net/20.500.11937/73948 |