Dr. Nicole Andeen is a renal and surgical pathologist at Oregon Health & Science University. She loves all things kidney.
Anti-glomerular basement membrane (anti-GBM) disease presents as a rapidly progressive glomerulonephritis (RPGN) with or without pulmonary hemorrhage, and is characterized by a diffusely crescentic GN, bright linear staining of glomerular basement membranes for polyclonal Immunoglobulin G (IgG), and an accompanying anti-GBM antibody in serum. This case highlights the features of atypical anti-GBM nephritis, and how they differ from classic anti-GBM nephritis.
A 74-year-old woman with a history of well-hypertension and psoriasis experience a progressive rise in serum creatinine over 6 months (from 0.7 to 2.0 mg/dL), with subsequent development of hematuria and scant proteinuria (200 mg/g on urine protein to creatinine ratio). Serologic workup including antinuclear antibody (ANA), double stranded DNA (dsDNA), antineutrophil cytoplasmic antibodies (ANCA), anti-GBM, hepatitis B and C, C3 and C4 levels, and serum electrophoresis with immunofixation were negative/normal.
Kidney biopsy revealed a limited sample of glomeruli with segmental endocapillary hypercellularity and no significant mesangial expansion, necrosis, crescents, or segmental sclerosis. By immunofluorescence, there was diffuse linear staining of glomerular basement membranes and focal tubular basement membrane for IgG and kappa light chain, without significant staining for lambda light chain or other immunoreactions. IgG subclass studies confirmed monotypic staining for IgG1 kappa, without staining for IgG2, IgG3 or IgG4. A DNAJB9 stain was negative, providing evidence against fibrillary glomerulonephritis. Electron microscopy revealed segmental subendothelial expansion and remodeling, moderate podocyte foot process effacement, and no deposits. This constellation of findings is diagnostic of atypical anti-GBM nephritis.
Atypical anti-GBM nephritis is diagnosed with one tenth the frequency of classic anti-GBM, and is clinically characterized by a milder and more chronic course, lack of pulmonary hemorrhage, and absent alpha3NC1 antibodies by commercial anti-GBM ELISA testing. Histologically, glomeruli can have a variety of injury patterns—including focal crescents, endocapillary or mesangial proliferation—but lack the diffuse crescentic phenotype of classic anti-GBM. Up to half the reported cases appear monoclonal by immunofluorescence, and a subset of these patients have a detectable monoclonal protein and/or plasma cell dyscrasia.
The mechanism of disease development is unknown, but distinct from classic anti-GBM disease; repeat biopsies in affected patients show relatively similar features without progression to a diffusely crescentic glomerulonephritis.
Optimal treatment is not established, although treatment regimens include rituximab and other immunosuppressive therapy. The described patient received rituximab and has stable kidney function at 1 year follow up. Overall outcomes are much better than for classic anti-GBM, with 85% of patients retaining kidney function at 1 year.
– Post prepared by Nicole Andeen