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

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; 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.

Severity of foot process effacement is associated with proteinuria in patients with IgA nephropathy

“…Our result was consistent with this previous study. Their subsequent study showed that CD68 infiltrates were associated with E score, suggesting that the pathogenesis of more severe proteinuria in patients with E score was correlated with renal inflammation [25]. They also reported a significant association between E and C scores.…”

The Utility of Assessing CD68+ Glomerular Macrophages in Assessing Endocapillary Hypercellularity in IgA Nephropathy

“…Recently the reproducibility of the E score between pathologists has been questioned. [ 5 ] Bellur et al . in their study reported that the reproducibility for endocapillary hypercellularity and mesangial proliferation between local and central pathologists was poor.…”

“…Aberrant immunoexpression of CD68 in non-human myeloid-derived cells is more frequent for clones KP1 and EBM11 in cryostat sections in comparison to the clone PG-M1 which was used by Soares et al . [ 5 ] to assess the E score. However, in our study cytoplasmic positivity for CD 68 was recorded strictly in an endocapillary lumen in mononuclear cells with histomorphological characteristics of macrophage.…”

“…[ 4 ] The Oxford Classification E score (endocapillary hypercellularity) carries prognostic significance and can predict renal function deterioration in IgAN patients but is poorly reproducible. [ 5 ] Macrophage infiltration is often seen in glomerular injury and hence, identification of glomerular macrophages by immunohistochemistry (IHC) might assist in identifying endocapillary hypercellularity.…”

Differentiating Staphylococcus infection-associated glomerulonephritis and primary IgA nephropathy: a mass spectrometry-based exploratory study

“…Immunostaining for lysozyme, S100A9 and CD68 was performed on individual tissue sections. Positively stained cells within the glomerular capillary tuft were manually counted using criteria described by Soares et al 53 . A positive cell was defined by clearly delimited aggregates of brown-stained cytoplasmic granules with or without a juxtaposed nucleus.…”