In class IV (“diffuse LN”), the lesions are qualitatively similar to those of Class III but involve 50% or more of all glomeruli. In addition, there is often a more diffuse distribution of the subendothelial immune deposits. When the subendothelial deposits are prominent enough to be seen by light microscopy, they impart a classic “wire-loop” appearance to the glomerular capillaries. As in class III, mesangial alterations may or may not be present.

Class IV is further subdivided into diffuse segmental (IV-S) LN when 50% or more of the involved glomeruli have segmental lesions, or diffuse global (IV-G) LN when 50% or more of the involved glomeruli have global lesions. The “A” and “C” modifiers are again used to designate active or chronic lesions.

Patients with class III or IV lesions often have prominent clinical manifestations including glomerular hematuria, marked proteinuria, hypertension, and renal insufficiency. Urine sediment often contains dysmorphic RBCs and red blood cell casts.

In class V (“membranous LN”), there is a global or segmental distribution of subepithelial immune deposits (or their morphologic sequelae), which are visible on light microscopy along with either immunofluo rescence or electron microscopy. The subepithelial changes associated with immune complex deposition resemble those of primary membranous nephropathy (see Plate 4-13); however, unlike in primary membranous nephropathy, membranous LN frequently features mesangial immune complex deposits as well.

Because the subepithelium is a major component of the protein diffusion barrier, patients with type V disease usually have more severe proteinuria than those with the other disease classes. Frank nephrotic syndrome is common and increases the risk of thromboembolic disease. In up to 40% of patients, however, proteinuria remains subnephrotic. Because circulating immune cells do not have access to the subepithelial antibodies, in pure class V LN the urine sediment is typically less active than in class III or IV disease. Note, however, that class V disease can occur in combination with class III or IV disease.