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Art of Medicine: Segmental Membranous Glomerulopathy

Tiffany Caza, MD, PhD renal pathologist at arkana laboratories
By Tiffany Caza, MD

Jul 02, 2021

segmental membranous nephropathy (MN) Art of Medicine painting

The painting depicts a silver stain of a glomerulus, showing thickened capillary loops with segmental ‘holes’, consistent with a segmental membranous nephropathy (MN). An IgG immunofluorescence image and an electron photomicrograph showing segmental immune deposits are shown below.


segmental membranous nephropathy (MN) Art of Medicine painting

IgG staining in a segmental distribution within a glomerulus, note capillary loop sparing.


segmental membranous nephropathy (MN) Art of Medicine painting

Ultrastructural evaluation of a glomerulus shows capillary loops with and without subepithelial electron-dense deposits.


The majority of MN cases show diffuse and global IgG staining, with segmental subepithelial immune deposits seen in only 2.5% of all MN biopsies.  In a recent case series, of all cases of segmental MN, 29% were found to be positive for neural epidermal growth factor-like 1 (NELL1, Kudose et al 2021), and no cases were positive for phospholipase A2 receptor (PLA2R), thrombospondin-type 1 domain containing 7A (THSD7A), or exostosin 1 (EXT1).  NELL1 is a recently described autoantigen in MN (Sethi et al, 2020) and is the second most common antigen type.  NELL1-positive MN frequently lacks diffuse and global granular capillary loop IgG staining, with segmental to incomplete global capillary loop deposits seen in 94% of cases.   Approximately one-third of patients with NELL1-positive MN have an underlying malignancy and NELL1 is thought to be a major autoantigen in malignancy-associated membranous nephropathy (Caza et al, 2021).   A segmental pattern of IgG in a membranous case can alert the pathologist to perform NELL1 staining, as a positive result may alert the clinician to do a thorough work-up to evaluate for an underlying malignancy.

Besides NELL1-positive MN, other etiologies for segmental MN include IgG4-related kidney disease, anti-brush border antibody disease, and MN in the setting of MPO-ANCA-associated glomerulonephritis.  Segmental MN overall carries a good prognosis, with 71% of patients showing partial or complete remission, often in the absence of immunosuppressive therapy (Kudose et al 2021).


  1. Kudose S, Santoriello D, Debiec H, Canetta PA, Bomback AS, Stokes MB, Batal I, Ronco P, D’Agati VD, Markowitz GS.  The clinicopathologic spectrum of segmental membranous glomerulopathy.  Kidney International 2021 Jan; 99 (1): 247-255.
  2. Caza TN, Hassen SI, Dvanajscak Z, Kuperman M, Edmondson R, Herzog C, Storey A, Arthur J, Cossey LN, Sharma SG, Kenan DJ, Larsen CP.  NELL1 is a target antigen in malignancy-associated membranous nephropathy.  Kidney International 2021; 99 (4): 967-976.
  3. Sethi S, Debiec H, Madden B, Charlesworth MC, Morelle J, Gross LA, Ravindran A, Buob D, Jadoul M, Fervenza FC. Ronco P.  Neural epidermal growth factor-like 1 protein (NELL-1) associated membranous nephropathy.  Kidney International 2020; 97 (1): 163-174.


Quick note: This post is to be used for informational purposes only and does not constitute medical or health advice. Each person should consult their own doctor with respect to matters referenced. Arkana Laboratories assumes no liability for actions taken in reliance upon the information contained herein.