What are intramembranous deposits in membranoproliferative glomerulonephritis?

Intramembranous Deposits in Membranoproliferative Glomerulonephritis

Intramembranous deposits in membranoproliferative glomerulonephritis (MPGN) are electron-dense deposits located within the glomerular basement membrane (GBM) itself, and when present, they are most characteristic of dense deposit disease (DDD), a subtype of C3 glomerulopathy, rather than typical immune-complex mediated MPGN. 1

Key Distinguishing Features

In Immune-Complex MPGN

• Intramembranous deposits can occur but are not the predominant finding 1
• When present in immune-complex MPGN, these deposits appear alongside the more typical subendothelial deposits (which are the hallmark location) 1
• The deposits in immune-complex MPGN are discrete, well-defined, and granular in appearance 1
• Some patients with endocapillary proliferative and membranoproliferative patterns show capillary wall deposits that are usually subendothelial, and only in some patients also intramembranous and subepithelial 1

In Dense Deposit Disease (C3 Glomerulopathy)

• Intramembranous deposits are the defining ultrastructural feature 1, 2
• These deposits are highly osmiophilic (appear very dark/electron-dense on electron microscopy) 1, 2
• They form continuous, ribbon-like deposits along large segments of the GBM 1, 2
• The deposits appear ill-defined, confluent, and less discrete compared to immune-complex deposits 1
• This creates a characteristic "sausage-like" thickening of the GBM 1

Clinical Significance and Diagnostic Approach

Why This Distinction Matters

The presence and characteristics of intramembranous deposits fundamentally change your diagnostic workup and treatment approach:

• If intramembranous deposits are highly osmiophilic, continuous, and confluent → Diagnose as dense deposit disease (DDD) and work up the alternative complement pathway 1, 2, 3
• If deposits are discrete, granular, predominantly subendothelial with only occasional intramembranous deposits → Diagnose as immune-complex MPGN and work up for infections, autoimmune diseases, and monoclonal gammopathy 1, 3

Complement Testing in DDD

When you identify the characteristic intramembranous deposits of DDD, you must evaluate for complement dysregulation 3, 4:

• Check for C3 nephritic factor (autoantibody against C3 convertase of the alternative pathway) 4
• Screen for mutations in factor H gene 4
• Measure serum membrane attack complex levels 3
• Perform alternative pathway functional assays 3

Immunofluorescence Pattern

The immunofluorescence pattern helps confirm your electron microscopy findings 2, 5:

• DDD shows dominant or isolated C3 staining with minimal or absent immunoglobulin 2
• This creates characteristic "mesangial rings" and double linear staining along capillary walls 5
• Immune-complex MPGN shows C1q, C3, and/or C4 deposits along with immunoglobulins 6

Common Pitfalls

Recognition Challenge

Not all cases with intramembranous deposits are easily recognized on light microscopy 5:

• In focal segmental necrotizing variants of DDD, dense intramembranous deposits may not be visible even under oil immersion 5
• You must rely on immunofluorescence showing segmental double linear C3 staining and "mesangial rings" to suspect the diagnosis 5
• Electron microscopy remains the diagnostic gold standard and may reveal only occasional peripheral loop deposits in atypical presentations 5

Terminology Evolution

The older classification of "MPGN type II" has been replaced by "dense deposit disease" because the light microscopic features are variable and the term better reflects the pathognomonic ultrastructural finding 5, 7, 6