Relationship between renal CD68 + infiltrates and the Oxford Classification of IgA nephropathy

Maria F. Soares, Vera Genitsch, Aron Chakera, Andrew Smith, Clare MacEwen, Shubha S. Bellur, Nasullah K. Alham, Ian S.D. Roberts

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Abstract

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; r 2  = 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, r 2  = 0.64, P < 0.0001). Digital image analysis revealed that tubulointerstitial CD68-positive cells correlated moderately with % TA/IF (r = 0.59, r 2  = 0.35, P < 0.001) and GFR at the time of biopsy (r = 0.54, r 2  = 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.

Original languageEnglish
Pages (from-to)629-637
Number of pages9
JournalHistopathology
Volume74
Issue number4
DOIs
Publication statusPublished - 1 Mar 2019

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Immunoglobulin A
Kidney
Biopsy
ROC Curve
Atrophy
Fibrosis
Mesangial Cells
Sclerosis
Immunosuppressive Agents
Area Under Curve
Microscopy
Cell Count
Steroids
Inflammation
Light
Sensitivity and Specificity
Therapeutics

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Soares, M. F., Genitsch, V., Chakera, A., Smith, A., MacEwen, C., Bellur, S. S., ... Roberts, I. S. D. (2019). Relationship between renal CD68 + infiltrates and the Oxford Classification of IgA nephropathy. Histopathology, 74(4), 629-637. https://doi.org/10.1111/his.13768
Soares, Maria F. ; Genitsch, Vera ; Chakera, Aron ; Smith, Andrew ; MacEwen, Clare ; Bellur, Shubha S. ; Alham, Nasullah K. ; Roberts, Ian S.D. / Relationship between renal CD68 + infiltrates and the Oxford Classification of IgA nephropathy. In: Histopathology. 2019 ; Vol. 74, No. 4. pp. 629-637.
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abstract = "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; r 2  = 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, r 2  = 0.64, P < 0.0001). Digital image analysis revealed that tubulointerstitial CD68-positive cells correlated moderately with {\%} TA/IF (r = 0.59, r 2  = 0.35, P < 0.001) and GFR at the time of biopsy (r = 0.54, r 2  = 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.",
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Soares, MF, Genitsch, V, Chakera, A, Smith, A, MacEwen, C, Bellur, SS, Alham, NK & Roberts, ISD 2019, 'Relationship between renal CD68 + infiltrates and the Oxford Classification of IgA nephropathy' Histopathology, vol. 74, no. 4, pp. 629-637. https://doi.org/10.1111/his.13768

Relationship between renal CD68 + infiltrates and the Oxford Classification of IgA nephropathy. / Soares, Maria F.; Genitsch, Vera; Chakera, Aron; Smith, Andrew; MacEwen, Clare; Bellur, Shubha S.; Alham, Nasullah K.; Roberts, Ian S.D.

In: Histopathology, Vol. 74, No. 4, 01.03.2019, p. 629-637.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Relationship between renal CD68 + infiltrates and the Oxford Classification of IgA nephropathy

AU - Soares, Maria F.

AU - Genitsch, Vera

AU - Chakera, Aron

AU - Smith, Andrew

AU - MacEwen, Clare

AU - Bellur, Shubha S.

AU - Alham, Nasullah K.

AU - Roberts, Ian S.D.

PY - 2019/3/1

Y1 - 2019/3/1

N2 - 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; r 2  = 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, r 2  = 0.64, P < 0.0001). Digital image analysis revealed that tubulointerstitial CD68-positive cells correlated moderately with % TA/IF (r = 0.59, r 2  = 0.35, P < 0.001) and GFR at the time of biopsy (r = 0.54, r 2  = 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.

AB - 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; r 2  = 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, r 2  = 0.64, P < 0.0001). Digital image analysis revealed that tubulointerstitial CD68-positive cells correlated moderately with % TA/IF (r = 0.59, r 2  = 0.35, P < 0.001) and GFR at the time of biopsy (r = 0.54, r 2  = 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.

KW - glomerulonephritis

KW - IgA nephropathy

KW - macrophages

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DO - 10.1111/his.13768

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JO - Histopathology

JF - Histopathology

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