By Donna J. Lager, M.D.
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease caused by immune dysregulation and affects essentially all organ systems in the body. Renal disease is observed in most patients with SLE at some point in the course of their disease and nearly 50% of all patients with SLE develop renal disease in the first year of diagnosis.
Renal biopsy in patients with SLE and any clinical evidence of renal disease is important for diagnosis and further management. In addition to establishing the initial diagnosis, the biopsy is also useful in determining levels of activity and chronicity and theseverity of disease. The initial biopsy also serves as a baseline biopsy with which to compare subsequent biopsies during thecourse of disease and to guide further therapy.
The first classification system of the glomerular lesions in lupus nephritis was formulated in 1974 under the auspices of theWorld Health Organization. It was later modified and revised in 1982 and again in 1995. The latest revision of the classificationof lupus nephritis was sponsored by the International Society of Nephrology (ISN) and the Renal Pathology Society (RPS) in2003 and was published in 2004 (1, 2). The ISN/RPS classification system is the subject of this newsletter.
Pathology of Lupus Nephritis
Nearly all compartments of the kidney are affected in SLE associated renal disease including the glomeruli, the tubules and interstitium and the renal vasculature. The lesions are predominantly inflammatory and can manifest in the glomeruli as mesangial and/or endocapillary proliferation, in the tubulointerstitial compartment as tubulointerstitial nephritis, often withtubular basement membrane immune deposits and in the vasculature as thrombosis or a necrotizing arteritis.
The glomerular lesions are classified into five classes according to the presence and distribution of immune deposits and theconsequent proliferative pattern (classes I-IV) or capillary wall response (class V) as well as the presence or absence of sclerosing(C) or active (A) lesions or both (A/C). A sixth class (VI) is characterized by advanced sclerotic disease (> 90% of glomeruli)without any activity. The morphologic characteristics of each class are summarized below, and classes II through V are illustratedin the accompanying TABLE.
Class I: Minimal mesangial lupus nephritis
The glomeruli appear normal by light microscopy; however mesangial immune deposits are present.
Class II: Mesangial proliferative lupus nephritis
The glomeruli show mesangial hypercellularity with any degree of mesangial matrix expansion, and mesangial immune deposits.A few capillary wall deposits may be visible by immunofluorescent staining or by electron microscopy.
Class III: Focal lupus nephritis
Fewer than half of all glomeruli contain active or inactive, segmental or global proliferative lesions. These may be active (A)lesions with endocapillary or extracapillary (crescentic) proliferation or inactive, segmental sclerosing lesions (C). Segmentallesions are those that involve less than half of the glomerular tuft.
Class IV: Diffuse lupus nephritis
In this class 50% or more of the glomeruli have active or inactive, segmental or global proliferative lesions as above, that involve 50% of the glomerular tuft (Global, G). The lesions may be active (A), inactive/chronic (C) or both (A/C).
Class V: Membranous lupus nephritis
The glomeruli contain global or segmentally distributed subepithelial immune deposits usually with mesangial deposits. This classmay occur in combination with Class III or IV lupus nephritis.
Class VI: Advanced sclerotic lupus nephritis
Over 90% of the glomeruli are globally sclerotic without residual activity.
Biopsy Reporting in Lupus Nephritis
The renal biopsy report must communicate clearly everything necessary to guide management and to assist in predicting prognosis. The current biopsy should be compared with any prior biopsies and the differences noted in the report.The report should include an assessment of the number of glomeruli in each sample including the number that are globallysclerotic, the glomerular lesion(s) present, the extent of involvement (focal, diffuse, global, segmental), the degree of activity and chronicity including the presence of necrotizing and crescentic lesions and sclerotic segments, and the presence of interstitial, tubular and vascular disease. A summary of findings and correlation with available clinical and laboratory data should be included in a comment. Representative images of pertinent biopsy findings within the report are also helpful.
References:
1. Weening JJ. et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney International 65:521-530, 2004.
2. Weening JJ, et al. The Classification of Glomerulonephritis in Systemic Lupus Erythematosus Revisited. J Am Soc Nephrol 15:241-250, 2004.
Date of last revision: March 2011.