IgA nephropathy or Berger’s disease is the most common cause of glomerulonephritis in the world. Rarely seen in blacks, this dis-ease afflicts mainly Asians and Caucasians. Clinical features include gross hematuria (40–50 percent), microscopic hematuria (30–40 percent), and rarely, renal insuffi-ciency with edema and hypertension (less than 10 percent). These usually occur after a respiratory infection. Minimal protein-uria is noted. IgA nephropathy is made by kidney biopsy only. The hallmark of this disease is mesangial deposition of IgA, which is prominently noted on immuno-fluorescence. This deposition is associated with focal mesangial expansion, which can be seen on light microscopy. Electron microscopy confirms the presence of elec-tron-dense deposits in the mesangium, which correspond to the immune complex deposits. An abnormality in the regula-tion of IgA may exist because of an envi-ronmental stimuli. This is supported by higher circulating levels of IgA in about 50 percent of cases, circulating immune com-plexes that parallel the duration of the dis-ease, and increased number of IgA-specific B and T lymphocytes. Its strong association with respiratory infection has led authori-ties to believe that mucosal immunity plays a role in this disease. Exaggerated muco-sal IgA response or decreased clearance may explain the elevated levels of plasma IgA in this disease. In the glomeruli, IgA-containing immune complexes activate the alternative complement pathway but do not bind C1, which may slow the removal of circulating complexes and thereby pro-mote deposition in the glomeruli.
The role of fibronectin and uteroglobin (an anti-inflammatory protein) in IgA nephropathy remains unclear. Most of the IgA-containing complexes are bound to fibronectin. In experimental animals, uteroglobin–fibronectin heteromerization prevented formation of fibronectin–IgA complexes and binding to glomeruli. Dele-tion of the uteroglobin gene in mice by gene knockout or suppression of the uteroglobin gene by antisense technology has histolog-ical features similar to IgA nephropathy. Interestingly, polymeric but not monomeric IgA binds only to mesangial cells, which stimulate release of IL-6, further leading to mesangial expansion.
IgA nephropathy usually follows a benign course, although about 15 per-cent of cases may reach end-stage renal disease at ten years and 20 percent at twenty years. Clinical and histopatho-logical predictors of progression of renal disease include worsening proteinuria (>1 g/day of proteinuria) and biopsy findings of glomerular sclerosis, tubular atrophy, interstitial fibrosis, and crescent forma-tion. Treatment of IgA nephropathy has radically changed over the past decade. Aggressive use of angiotensin-converting enzyme (ACE) with and without angio-tensin-receptor blocker (ARB) is recom-mended to decrease the proteinuria and for their renoprotective properties. Cyto-toxic agents and steroids are reserved for aggressive renal disease.