IgA nephropathy: recent developments.

IgA nephropathy (IgAN), a mesangial proliferative glomerulonephritis (GN), is the most common GN in all parts of the world where renal biopsy is widely practiced. It is unique among glomerular diseases in being defined by immunohistochemical findings, i.e., mesangial deposition of IgA, rather than by light microscopy. Because the clinical features of IgAN were discussed in 1997 (1), we focus on recent developments in IgAN. Henoch-Schonlein purpura (HSP) is an IgA-mediated systemic vasculitis in which the glomerular disease may be indistinguishable from IgAN. IgAN seems to be a kidney-restricted form of HSP. HSP is not discussed in detail here; the reader is referred to the recent review by Rai and colleagues (2). Clinical Presentation In the great majority of cases, IgAN is an isolated renal disease with no apparent clinical antecedent or association— primary IgAN. As well as the association with IgA-mediated systemic vasculitis in HSP, there are a number of other clinical contexts that seem to predispose to IgAN, usually called secondary IgAN. Among the best characterized associations are those with rheumatoid arthritis, ankylosing spondylitis, and Reiter’s syndrome; celiac disease and dermatitis herpetiformis; chronic liver disease (especially alcohol induced); and viral diseases, particularly HIV infection and hepatitis B (in endemic areas). However, caution should be exercised in interpreting some other associations as causal. There are many anecdotal reports of single cases that may reflect merely chance associations with a disease as common as IgAN. Approximately 40 to 50% of patients present with recurrent macroscopic hematuria, which usually coincides with mucosal infection or exercise. This feature is virtually never seen after the age of 40 yr. Asymptomatic hematuria with or without proteinuria is the presentation in 30 to 50% of most series. There is an “iceberg” effect in the apparent prevalence of this presentation—the extent to which only the tip of the iceberg is identified as having IgAN being decided by local attitudes toward urine testing and renal biopsy. Nephrotic syndrome is unusual, being the presentation in only 5% of all IgAN. Uncommon but well described is the coincidence of IgAN and minimal change disease in both adults and children. Acute renal insufficiency is uncommon in IgAN, occurring in only 5% of cases. It is described in association with macroscopic hematuria, although this is an infrequent clinical problem even when hematuria is heavy. Alternatively, it may be due to crescentic IgAN. To distinguish between these two clinical settings, renal biopsy is mandatory in acute renal insufficiency unless recovery of renal function is rapid. By analogy with pauci-immune crescentic nephritis, a number of investigators have sought evidence of IgA-antineutrophil cytoplasmic antibodies (ANCA) in both IgAN, particularly crescentic IgAN, and HSP. Although there are a number of cases in which IgA-ANCA seems to be associated with active disease, overall findings are inconsistent. This may in part reflect methodologic differences. However, on occasion, patients with IgAN or HSP have circulating IgG-ANCA, and in some the diagnostic criteria for microscopic polyangiitis or Wegener’s granulomatosis are met. These patients respond to immunosuppressive therapy (3). A few patients with linear capillary wall IgA deposition have also been described, presumably an IgA-mediated variant of Goodpasture syndrome (4). Approximately 10 to 20% of patients with IgAN present with established chronic renal insufficiency. It is usually assumed that these patients have long-standing disease that differs from the classic presentations only because the patient did not come early to medical attention.