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Relationship between renal CD 68 + infiltrates and the Oxford Classification of IgA nephropathy
Author(s) -
Soares Maria F,
Genitsch Vera,
Chakera Aron,
Smith Andrew,
MacEwen Clare,
Bellur Shubha S,
Alham Nasullah K,
Roberts Ian S D
Publication year - 2019
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13768
Subject(s) - nephropathy , pathology , medicine , creatinine , urology , gastroenterology , endocrinology , diabetes mellitus
Aims The Oxford Classification E score (endocapillary hypercellularity) predicts renal functional decline in IgA nephropathy (Ig AN ) patients free from steroid/immunosuppressive ( IS ) therapy, but is poorly reproducible. We hypothesise that endocapillary hypercellularity reflects glomerular inflammation and that the presence of CD 68‐positive cells is a more robust marker of E score. Methods and results CD 68‐positive cells were quantified in glomeruli and tubulointerstitium in biopsies from 118 Ig AN 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 CD 68 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 CD 68‐positive cells and mesangial hypercellularity, % segmental sclerosis, % of crescents and % tubular atrophy/interstitial fibrosis ( TA / IF ). ROC curve analysis demonstrated that a maximum glomerular CD 68 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 CD 68‐count >6 was reproducible (kappa score 0.8), and there was a strong correlation between glomerular CD 68 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 CD 68‐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 CD 68‐positive cells emerge as markers of endocapillary hypercellularity, their tubulointerstitial counterparts are associated with chronic damage.