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
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)
Normal glomeruli by LM but mesangial
immune deposits by IF
Mesangial proliferation and/or
expansion by LM with mesangial immune deposits by IF and/or
EM without endocapillary proliferation
- segmental or global; focal subendothelial immune complexes,
+/- mesangial alterations
- active (IIIA), or sclerosing (IIIC) or combined (IIIA/C)
- diffuse subendothelial immune complexes, +/- mesangial
- 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])
- global or segmental subepithelial immune deposits, +/-
- may show advanced sclerosis
- may co-exist with Class III or Class IV (report both)
Sclerosis affecting >90% of glomeruli
globally without residual activity
(LM – Light Microscopy, IF – Immunofluorescence
Microscopy, EM – Electron Microscopy)
- 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.
- Churg J, Sobin LH: Lupus Nephritis. In: Renal disease, classification
and atlas of glomerular diseases. Edited Tokyo ; New York , Igaku – Shoin,
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NewsPath® Editor: Megan
J. DiFurio, MD, FCAP
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