Immunoglobulin A Nephropathy

Immunoglobulin A nephropathy (IgAN) is the most common form of primary chronic glomerular disease worldwide. First described in 1968 by pathologist Jean Berger, it was regarded for many years as a benign condition. However, the widespread use of kidney biopsy has provided better insight into its full consequences, demonstrating it to be an important chronic, slowly progressive cause of end-stage renal disease in the pediatric population, leading eventually to renal failure in many patients. An immune complex–mediated nephropathy, IgAN is defined immunohistologically by the presence of glomerular IgA deposition accompanied by a mesangial proliferative glomerulonephritis.

IgAN is most common in white and Asian populations, with a peak incidence in the second and third decades of life. The annual incidence in the United States is reported to be 0.5 pediatric cases per 100,000. In Japan, remarkably, the incidence is 10 times as high, but worldwide the highest incidence of IgAN is in Southeast Asia. This is thought to result at least in part from increased screening for urinary abnormalities and a lower threshold for renal biopsy in patients with asymptomatic microscopic hematuria, leading to increased diagnosis. The 2:1 male/female predominance in North America and Western Europe is not seen in Asian populations. Although the true prevalence of IgAN remains unknown, its prevalence has been inferred from the proportion of cases identified in large series of kidney biopsies.

The current understanding of IgAN’s pathogenesis, referred to as the multi-hit hypothesis, is that the disease arises as a consequence of multiple sequential pathogenic “hits.” IgA, the most abundant antibody in humans, exists in 2 isoforms, IgA1 and IgA2, present in secretions and on …