Using 100 serial sections for light microscopy, we studied the clinicopathologic character istics of IgA nephropathy with severe proteinuria. Eight out of 128 cases with IgA nephrop athy exhibited severe proteinuria of 3.0g/day or more. These cases consisted of 5 males and 3 females with an age range from 15 to 73 years. Daily proteinuria ranged from 3.3 to 7.1 g. At the time of biopsy, the serum creatinine level was 1.2 mg/dl or more in 6 cases; two of these developed end-stage renal failure during the follow-up period. In most of the cases, routine sections for light microscopy revealed moderate to severe mesangial proliferation and tubulointerstitial damage. In 7 cases, variable percentages of glomeruli, ranging from 20% to 95%, were involved by chronic lesion represented by sclerosis and fibrous crescents/adhesion, while only 2 cases exhibited active lesion characterized by segmental glomerular necrosis and/or cellular/fibrocellular crescents. In contrast, thorough observation of 100 additional serial sections disclosed the focal presence of active lesion in all except one case with features of endstage kidney. In addition, the highest precentage of glomeruli with active lesion in the serial sections correlated well with the severity of proteinuria. The results suggested that severe proteinuria in IgA nephropathy depends on, at least in part, focal outbreak of active lesion characterized by segmental glomerular necrosis and cellular/ fibrocellular crescents.
