The Pathology of Early Recurrent Membranous Glomerulonephritis (MGN)
EF Rodriguez, FG Cosio, S Sethi, SH Nasr, ME Fidler, LD Cornell. Mayo Clinic, Rochester, MN
Background: MGN in the native kidney is characterized clinically by proteinuria and morphologically by subepithelial glomerular basement membrane (GBM) deposits of IgG and C3 by immunofluorescence (IF), subepithelial deposits visible by electron microscopy (EM), and diffuse podocyte foot process effacement (FPE). MGN may recur in the allograft and cause graft loss. Protocol and early indication biopsies allow detection of recurrence before it is clinically apparent. In this study we assessed the earliest morphologic manifestations of MGN in humans.
Design: Kidney transplant biopsy records from 2006-present at our institution were reviewed for cases of early recurrent MGN. Clinical data, IF reports, and EM were reviewed at the initial biopsy with evidence of recurrent MGN and on follow-up biopsies.
Results: Eight patients (F=5, M=3), were identified with early recurrent MGN on protocol (n=4) or indication (n=4) biopsy, with a total of 20 initial and follow-up biopsies. The mean age at the time of transplant was 48 yrs (range, 27-56 yrs). 7 patients were on routine maintenance triple immunosuppressive therapy; one was on a steroid-free protocol with tacrolimus and mycophenolate. The mean time of biopsy post-transplant with pathologic changes was 3.2 mos (range, 0.5-12; median 2.2). In each patient's earliest biopsy, IF showed granular GBM staining for C4d, IgG, and kappa and lambda light chains (8/8 cases). IF for C3 was negative (5/8) or showed trace segmental GBM staining (3/8). On each patient's earliest MGN biopsy positive by IF, 6/8 showed absence of detectable deposits by EM and 6/8 showed no significant podocyte FPE. Only 2/8 cases showed diffuse podocyte FPE; one showed small deposits by EM, and the other showed no deposits. Of the 6 patients that showed absent deposits by EM on the early biopsy, half (3/6) later developed tiny subepithelial deposits after a mean of 9 mos follow-up (range 6.7-13). At the time of the earliest MGN biopsy, the mean measured or predicted proteinuria was 0.94 g/day (range 0.17-2.3) in 7 patients without contaminating native kidney proteinuria.
Conclusions: Early recurrent MGN is characterized by C4d and IgG GBM deposits with absent or minimal C3, often no detectable deposits by EM and mild or no podocyte FPE, and minimal or mild proteinuria. Routine C4d staining in transplant biopsies may detect early recurrent MGN. Recognition of these unique features can aid in the diagnosis of early recurrent MGN before patients develop significant proteinuria.
Category: Kidney (does not include tumors)
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 228, Wednesday Afternoon