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ESSENTIALS OF DIAGNOSIS
IgA nephropathy is the most common form of glomerular disease in the world.
IgA nephropathy is characterized by frequent bouts of microscopic and/or macroscopic hematuria, often following an upper respiratory infection (URI).
The pathophysiology of IgA nephropathy is related to aberrant glycosylation of the IgA molecule.
The pathogenesis of IgA nephropathy is considered to involve a “multi-hit” model.
The diagnosis is established by kidney biopsy showing prominent globular deposits of IgA often accompanied by C3 and IgG in the mesangium.
There is no specific treatment of IgA nephropathy and 10–20% of patients with the disease will progress to end-stage kidney disease within 10 years of diagnosis, and 25–40% within 20 years.
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General Considerations
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IgA nephropathy (IgAN) is the most common form of glomerulonephritis in the developed world, yet despite this distinction, relatively little is known about noninvasive diagnostic as well as targeted treatment options. Patients may present at any age but the peak incidence is in second and third decade of life. The disease occurs with the greatest frequency in Asian and Caucasian races.
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First described in 1968, IgAN continues to be a diagnostic as well as treatment dilemma even though there has been steady progress elucidating the molecular biology of its pathogenesis. The “classic” presentation of microscopic hematuria and URI-induced macroscopic hematuria in an otherwise asymptomatic younger individual, after a negative urologic work-up, raises suspicion about the diagnosis. However, these are obviously nonspecific findings, thus with the current absence of serum or urine biomarkers, the only way to ensure a diagnosis is with an invasive kidney biopsy to include IgA immunofluorescence straining. Furthermore, there are as yet no targeted therapies which have been shown to be efficacious in this disease.
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The pathophysiology of IgAN is related to systemically decreased glycosylation of O-linked glycans in the hinge region of the IgA1 molecule, resulting in dysregulation and elevated serum levels of such galactose-deficient IgA1 (Gd-IgA1). Subsequently, these aberrant IgA1 molecules are deposited within the kidney mesangium leading to immune complex formation, promotion of cell growth, and production of proinflammatory cytokines, chemokines, and growth factors (Figure 28–1). Complement activation, stimulated by both polymeric IgA and Gd-IgA1, also plays a role in inflammation (although serum complement levels are generally not decreased). That IgAN is the manifestation of a systemic process is illustrated by the finding that this disease frequently recurs in kidney allografts in IgAN patients. However, the disease is cleared, from a pathological standpoint, in non-IgAN patients receiving IgAN kidneys.
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