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Essentials of Diagnosis

  • Immunoglobulin A nephropathy (IgAN) is the most frequent form of primary glomerulonephritis worldwide.
  • Hematuria is typical. Younger patients often present with episodes of macroscopic hematuria coincident with mucosal infections or exercise. Adults often have asymptomatic hematuria and proteinuria.
  • Abnormal glycosylation of immunoglobulin A (IgA) molecules is believed to be important in disease pathogenesis.
  • The diagnosis is established by the presence of dominant or codominant IgA deposition by immunofluorescence microscopy typically in the mesangial region of the glomeruli.
  • True IgA nephropathy is not just “benign recurrent hematuria.” End-stage renal disease (ESRD) occurs in 15% of patients by 10 years and 20–40% by 20 years from onset.

General Considerations

IgAN is the most common form of primary glomerulonephritis worldwide. The prevalence of the disease shows geographic variations. In patients who undergo renal biopsy, IgAN accounts for approximately 30–40% of cases in Asia, 15–20% of cases in Europe, and 5–10% of cases in North America. These differences may be attributed to true differences in genetic susceptibility, or just as likely to differences in urinalysis screening practices, indications for renal biopsy, and possibly other factors. The disease is more common in whites, Asians, and American Indians and less common in blacks both in the United States and in Africa. It is most frequently diagnosed in young adults in the second and third decade of life and there is a male predominance.

Although numerous putative specific environmental or infectious agents have been suggested as the underlying stimulus for IgAN, none has been conclusively confirmed in the majority of patients. Familial clustering and a higher risk in identical twins suggest a role for genetic factors in susceptibility. A variety of genetic polymorphisms associated with susceptibility (and/or progression) in IgAN have been reported with conflicting results. Although IgAN is most commonly a primary (or idiopathic) renal disease, there are well-documented associations with a wide variety of conditions in individual patients (Table 27–1). In many of these conditions, IgA deposition in the glomerulus is not associated with inflammation and a progressive course, and thus, it may be clinically insignificant. This suggests that factors beyond the deposition of IgA or IgA-containing immune complexes must be involved in the pathogenesis of progressive disease in patients with idiopathic IgAN.

Table 27–1. Diseases Associated with Immunoglobulin A (IgA) Nephropathy.

Pathogenesis

The precise etiology of IgAN is unknown, but much evidence suggests that a basic abnormality in the IgA molecule itself plays a pivotal role in pathogenesis. ...

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