Glomerular disease in LN is a dynamic process with the potential for glomerular lesions to transform from one pattern to another.1-4 Adjacent glomeruli may show different degrees of involvement. The widely accepted 2004 ISN/Renal Pathology Society (RPS) Classification of LN is highly reproducible, and predicts disease course and outcome.10 (Table 1)
ISN Class I denotes normal glomeruli by light microscopy but with mesangial immune deposits by immunofluorescence and electron microscopy. ISN CLASS II, which is mesangial proliferative LN, is characterized by mesangial hypercellularity demonstrated by LM, with greater than three mesangial cells in areas away from the vascular pole by LM as well as mesangial immune deposits.
ISN CLASS III is focal LN, defined as focal segmental and/or global endocapillary and/or extracapillary glomerulonephritis affecting less than 50% of the glomeruli. ISN Class IV is diffuse LN. It is characterized by segmental and/or global endocapillary and/or extracapillary glomerulonephritis affecting more than 50% of glomeruli.
Both Class III and IV have subendothelial immune deposits. LN Class IV is subdivided into diffuse segmental versus diffuse global proliferation, and both Class III and IV may have active A (proliferative), and inactive chronic C (sclerosing) lesions. ISN Class V is membranous LN defined by subepithelial immune deposits. SLE Patients may have combined lesions noted as Class III + V or IV + V. Class VI is defined as advanced sclerosing LN with more than 90% global glomerular sclerosis.
In LN, IgG staining on IF is almost always present and C1q is particularly common. “Full house staining” (the presence of IgG, IgA, IgM, and C3 and C1q – three of one kind and two of the other) is very suggestive of LN, as is IF deposition along the tubular basement membranes and the glomerular basement membranes. Likewise by EM, tubuloreticular inclusions (TRI)—24 nm interanastomosing tubular structures in the glomerular endothelial cells—are commonly found only in biopsies of patients with LN or in those with HIV infection.
With treatment or over time, serial biopsies often show transformation from one histologic class to another.4 In general, clinical renal manifestations correlate well with ISN biopsy class. Nephrotic patients with membranous lupus and lupus patients with antiphospholipid antibodies are particularly predisposed to thrombotic complications such as deep vein thrombophlebitis, renal vein thrombosis, and pulmonary emboli.20
Patients with ISN Classes I and II need no attention directed at their renal lesions. Some patients with very mild class III lesions can be treated with a short course of increased corticosteroids, which typically results in a good clinical and histologic response. For most patients with active proliferative LN, Class III and IV, it is useful to divide treatment into an induction phase and a maintenance phase.
The induction phase typically is used for uncontrolled, active renal disease that at times may be acutely life- or organ-threatening, whereas the maintenance phase focuses on the long-term management of chronic, relatively indolent disease, where avoidance of the adverse effects of therapy and prevention of flares become very important.