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    Epidemiology and Pathophysiology of Glomerular C4d Staining in Native Kidney Biopsies

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    Author
    Drachenberg, C.B.
    Papadimitriou, J.C.
    Chandra, P.
    Haririan, A.
    Mendley, S.
    Weir, M.R
    Rubin, M.F.
    Date
    2019
    Journal
    Kidney International Reports
    Publisher
    Elsevier Inc
    Type
    Article
    
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    https://doi.org/10.1016/j.ekir.2019.07.015
    Abstract
    Introduction: Routine C4d staining in renal transplantation has stimulated its use in kidney biopsies with glomerulonephritis (GN). Methodical description on staining patterns in the native kidney is not available. Methods: We retrospectively evaluated C4d staining in formalin-fixed paraffin-embedded sections from 519 native kidney biopsies (bx) with and without glomerular disease. Results: Strong C4d staining was consistently present in immune-complex GN, including lupus nephritis (LN) (n = 68), membranous GN (n = 24), membranoproliferative glomerulonephritis (MPGN) pattern (n = 22), fibrillary GN (n = 3), and proliferative GN with monoclonal IgG (n = 3). C4d stained all cases of postinfectious GN (n = 7) amyloidosis (n = 20) and C1q GN (n = 3). In contrast, IgA nephropathy (IgAN) (n = 34), was negative in 62% of bx, with the rest staining variably. The E1 Oxford classification score correlated with capillary wall C4d staining (P = 0.05). C4d marked the glomerular and arteriolar lesions in thrombotic microangiopathy (TMA; n = 16), the glomerular sclerotic segments in focal segmental glomerulosclerosis (FSGS; n = 77), and marked areas of necrosis in crescentic GN (n = 21). In diabetic glomerulopathy (n = 70), C4d marked advanced insudative lesions but was negative otherwise. C4d weakly stained the mesangium, or was negative in normal biopsies (n = 13), minimal change disease (MCD; n = 21), thin basement membrane disease (n = 20), Alport (n = 3), IgM nephropathy (n = 2), C3 glomerulopathy (n = 5), acute interstitial nephritis (n = 12), acute tubular necrosis (n = 22), ischemic glomerulopathy/nephrosclerosis (n = 23), and other miscellaneous processes (n = 14). Staining in tubular basement membranes and peritubular capillaries was most common in lupus. Conclusion: Based on reliable staining in lupus and membranous GN, C4d staining is potentially useful as a screening and diagnostic tool, if only paraffin-embedded tissue is available. Knowledge of C4d staining patterns in normal and pathological tissues enhances its diagnostic value.
    Keyword
    complement deposition
    diabetes mellitus
    glomerulonephritis
    IgA nephropathy
    immune deposits
    lupus nephritis
    membranous glomerulopathy
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85072596652&doi=10.1016%2fj.ekir.2019.07.015&partnerID=40&md5=e66a534637b92a1b21bc98094539e117; http://hdl.handle.net/10713/11035
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.ekir.2019.07.015
    Scopus Count
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    UMB Open Access Articles 2019

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