Familial IgA Nephropathy: Evidence of an Inherited Mechanism of Disease

The evaluation of familial glomerulonephritis in patients with IgA nephropathy who were from central and eastern Kentucky resulted in the discovery of potentially related pedigrees containing 14 patients. An additional 17 members of the pedigrees had clinical glomerulonephritis, and 6 had "chronic nephritis" noted on their death certificates. Six patients with IgA nephropathy had a common ancestor. In addition, both parents of six patients with the disease came from families with other cases of IgA nephropathy. No single HLA haplotype or antigen was found in all the patients with IgA nephropathy. Our data on these pedigrees strongly support an inherited mechanism in the pathogenesis of IgA nephropathy in some patients. (N Engl J Med 1985; 312:202–8.) IgA nephropathy was first described by Berger in 1969. 1 The disease is characterized pathologically by the deposition of IgA in the glomerular mesangium. At clinical presentation the disorder may be macroscopic hematuria, often recurring in association with viral upper respiratory illness or with microscopic hematuria or proteinuria (or both). The original concept that IgA nephropathy was a benign form of glomerulonephritis 2 3 4 5 has been reassessed in the light of numerous reports of progression to renal insufficiency. 6 7 8 9 10 The prevalence of the disease apparently varies greatly among different ethnic groups and nationalities. 1 2 3 , 7 , 8 , 11 , 12 Some of the identified pathogenic factors include circulating IgA-containing immune complexes, . . .