IgA Nephropathy: Insights into Genetic Basis and Treatment Options

Abstract

IgA nephropathy (IgAN), is the most common primary glomerulonephritis worldwide. On light microscopy the picture can vary from slight mesangial hypertrophy to extra capillary proliferation of glomeruli, with sclerosis and interstitial fibrosis. On immunofluorescence staining of kidney sections the disease is characterized by mesangial deposits of IgA, predominantly polymeric IgA (pIgA) of the IgA1 subclass, and often co-deposition of complement factor C3, properdin and IgG. It is important however to realize that, although IgA mesangial deposits are necessary for the diagnosis of IgAN, the latter is not obligatory in every individual with mesangial IgA deposits. Thus, IgA deposits may also be seen in subjects with no evidence of renal disease [Suzuki et al, 2003; Waldherr et al, 1989] at an incidence that ranges from 3 to 16 percent. Furthermore, there are also a number of reports documenting IgA deposition in other forms of glomerulonephritis, particularly thin basement membrane disease, lupus nephritis, minimal change disease, and diabetic nephropathy, a finding which is most probably casual rather than causal. IgAN occurs at any age, but most commonly the age of onset is in the second or third decade of life. Males are more often affected than females, with a male:female ratio of 2:1. Most patients with IgAN present microscopic hematuria with or without mild proteinuria. About 40% of patients have episodes of macroscopic hematuria. This is sometimes preceded by infections, most commonly upper respiratory tract infections, a phenomenon known as “synpharyngitic” hematuria. Other infections like gastrointestinal or urinary tract infections have also been reported to precede macroscopic hematuria. Proteinuria is common and can vary from mild proteinuria to nephrotic syndrome. IgAN has been considered a benign disease for a long time, but nowadays it is clear that 3040% of patients may develop renal failure with significant socioeconomical consequenses. In Western Europe and the United States of America 7-10% of the patients on renal replacement therapy suffer from IgAN. The severity of histological lesions, especially diffuse proliferative glomerulonephritis, marked capsular adhesions, fibrocellular crescents, glomerular hyalinosis and severe sclerosis, as well as tubulointerstitial damage correlate