College of American Pathologists
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New Classification of Lupus Nephritis

Posted December 1, 2005

Oyedele Adeyi, MB, BS
Surgical Pathology Committee

Definition of Terms :
Global – affecting the entire glomerulus
Segmental – affecting a part of each glomerulus
Focal – fewer than 50% of all glomeruli affected
Diffuse – more than 50% of all glomeruli affected

The kidney is one organ whose involvement by systemic lupus erythematosus (SLE) often defines the overall outlook of what is otherwise a systemic disease. Pathologic classification of lupus nephritis (LN) has evolved over the past 40 years; the aim being to obtain a morphologic description that is as close to ideal as possible in predicting clinical progression. The most recent 2003 classification is a modification of the previous WHO version, which had been in use since 1982.1,2 The changes being proposed emphasize the extent of glomerular inflammation or sclerosis, which most significantly affects Class III and Class IV LN of the WHO classification.

In the 1982 classification, Class III LN referred to segmental lesions in the glomeruli, even if they were diffusely affected, whereas Class IV LN described global lesions in glomeruli, even if only a minor proportion of glomeruli were so affected. Clinical evidence, however, indicates that the number of glomeruli visibly affected is a better predictor of progression than the severity of individual glomerular injury. As such, the current modification proposes that Class III LN include biopsies with both segmental and global lesions as long as the affected glomeruli are “focal”.

In the same vein, Class IV LN , which previously defined only global glomerular lesions irrespective of the proportion of glomeruli affected, now refers to both segmental or global glomerular injuries that are “diffuse”;. Simply put, Class III LN lesions are focal and Class IV LN lesions are diffuse. To differentiate between the segmental and global Class IV LN lesions, the letters “S” and “G” are used respectively to indicate if the diffuse lesions affect only segments of glomeruli (i.e., diffuse segmental lupus nephritis or Class IV-S), or if they affect glomeruli globally (i.e., diffuse global lupus nephritis or Class IV-G).

Lastly, the letters “A”, “C”, or “A/C” (standing for “active,” “chronic,” and combined “active and chronic”), are to be used to qualify Class III LN and Class IV LN lesions, if they are proliferative (i.e., “active”), sclerosing (i.e. ,“chronic”), or a combination of both.

There are only very minor changes proposed in the other classes of LN, and these are summarized in Table 1. One should acknowledge that no single classification is ideal in any situation. Pathologists nevertheless are relentless in working towards the ideal, as we better understand the disease process.

Table 1 : Summary of the Components of the International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 Classification of Lupus Nephritis

(Adapted from Weening et al.1)


Minimal mesangial LN:
Normal glomeruli by LM but mesangial immune deposits by IF


Mesangial Proliferative LN:
Mesangial proliferation and/or expansion by LM with mesangial immune deposits by IF and/or EM without endocapillary proliferation


Focal LN:

  • segmental or global; focal subendothelial immune complexes, +/- mesangial alterations
  • active (IIIA), or sclerosing (IIIC) or combined (IIIA/C)


Diffuse LN:

  • diffuse subendothelial immune complexes, +/- mesangial alterations
  • segmental (IV-S) or global (IV-G)
    • active (IV-S [A] or IV-G [A])
    • sclerosing (IV-S [C] or IV-G [C])
    • combined (IV-S [A/C] or IV-G [A/C])


Membranous LN:

  • global or segmental subepithelial immune deposits, +/- mesangial alterations
  • may show advanced sclerosis
  • may co-exist with Class III or Class IV (report both)


Advanced sclerosing LN:
Sclerosis affecting >90% of glomeruli globally without residual activity

(LM – Light Microscopy, IF – Immunofluorescence Microscopy, EM – Electron Microscopy)


  1. Weening JJ, D'Agati VD, Schwartz MM, et al. The Classification of Glomerulonephritis in Systemic Lupus Erythematosus Revisited. J Am Soc Nephrol. 2004;15(2):241-250.
  2. Churg J, Sobin LH: Lupus Nephritis. In: Renal disease, classification and atlas of glomerular diseases. Edited Tokyo ; New York , Igaku – Shoin, 1982:127-149

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NewsPath® Editor: Megan J. DiFurio, MD, FCAP
This newsletter is produced in cooperation with the College of American Pathologists Public Affairs Committee and may be reproduced in whole or in part as a service to the medical community. Copyright © 2006 by the College of American Pathologists.
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