IgA nephropathy was first described by Berger in France in 1968. The histologic picture is characterized by a mesangial proliferative glomerulonephritis in which mesangial deposits of IgA predominate, with variable amounts of C3 and lesser variable amounts of IgM or IgG. The cause is unknown. Clinical exacerbations immediately after viral illnesses do not clearly support an infectious cause. Soluble immune complexes containing IgA can be detected in the circulation, suggesting an immune complex etiology. Levels of dimeric IgA may be elevated in the blood, and the soluble immune complexes also contain IgA of mucosal origin, although IgA secretory piece has not been found in circulating immune complexes or in glomerular lesions. IgA can also be detected in the dermal capillaries of grossly normal skin in some patients, suggesting that IgA nephropathy may represent a dominant renal manifestation of a systemic disease (see later discussion of Henoch-Schönlein purpura). The circulating soluble immune complexes generally do not bind C1q, and C1q is not usually present in glomeruli, suggesting activation of complement by the alternative pathway.
Clinical Features
In North America, IgA nephropathy accounts for perhaps 10% of renal biopsies, but higher incidences are seen in Europe and Asia. There is a striking male predominance of 3:1 to 6:1. Few cases have been reported in blacks. HLA associations have been described with HLA-Bw35, HLA-B12, and HLA-DRw4. The disorder can be seen at any age but is most commonly discovered in young adults ages 15 to 30. The clinical presentation varies from asymptomatic microscopic hematuria or proteinuria to single or recurrent episodes of macroscopic hematuria with or without mild constitutional symptoms to idiopathic nephrotic syndrome to (rarely) fulminant RPGN.
Laboratory findings include elevated levels of IgA, IgAcontaining soluble immune complexes, and, occasionally, IgA class cryoglobulin in the blood. Serologic studies are otherwise not helpful. The urinary sediment is nearly always abnormal, but the degrees of proteinuria and hematuria can vary at different times and among different patients. Red blood cell casts are relatively common and may be present in large numbers, often in the absence of other types of urinary casts.
Causes
The relation of Henoch-Schönlein purpura and IgA nephropathy warrants comment. Henoch-Schönlein purpura is a systemic vasculitis characterized by nonthrombocytopenic purpura caused by a leukocytoclastic dermal vasculitis, plus variable involvement of joint and other serosal surfaces, the gastrointestinal tract, and the glomeruli. Nearly identical pathologic changes are seen in kidneys with Henoch-Schönlein purpura as in kidneys with IgA nephropathy. This fact and other similarities, such as elevated IgA levels, IgA in dermal capillaries of diseased skin, IgA-containing immune complexes, and often a course of exacerbations and remissions, have led most authors to conclude that IgA nephropathy is a form of Henoch-Schönlein purpura in which only renal features are clinically expressed.
Pathology
The glomeruli show expansion of the mesangial stalk with both increased cells and matrix . Peripheral basement membranes show little change. Some glomeruli may show crescents. With progression of the disease, individual lobules or entire glomeruli may become sclerotic. By definition, immunofluorescence studies show strong staining for IgA that occurs mainly in the mesangial region . IgA may also be present along portions of capillary loops. Weaker staining for C3, IgG, and IgM may be present in a similar distribution. Electron microscopy shows the presence of dense mesangial deposits of varying size. The deposits often extend from the mesangial region into the adjacent subendothelial space of capillary basement membranes. Patchy effacement of epithelial foot processes is often seen.
Course
Most patients with IgA nephropathy do well; however, urinary abnormalities persist, and 25% of patients eventually have renal failure. Occasional patients may have a more rapid course. Nephrotic levels of proteinuria, hypertension, and early renal insufficiency portend a worse prognosis.
