IgA nephropathy with minimal change disease

Abstract

Background and objectives: Patients with IgA nephropathy typically present with hematuria and subnephrotic proteinuria. Nephrotic syndrome is uncommon in IgA nephropathy, and when present, it is usually associated with severe histologic features, such as endocapillary proliferation, segmental sclerosis, and crescent formation. Rarely, patients with IgA nephropathy present with nephrotic syndrome and only mild mesangial disease. This study sought to better characterize these patients.

Design, setting, participants, & measurements: A retrospective review of cases of IgA nephropathy diagnosed from 2004 to 2011 identified patients with nephrotic range proteinuria and histologically mild IgA nephropathy. Specifically, using the Oxford Classification of IgA Nephropathy, we identified cases that lacked endocapillary proliferation or segmental sclerosis.

Results: The cohort consisted of 17 patients, including 10 men and 15 adults. The median serum creatinine was 0.9 mg/dl (range=0.7-3.1), median 24-hour urine protein was 8.0 g/d (3.0-18.0 g), and 14 patients were fully nephrotic, whereas the remaining 3 patients fulfilled two of three criteria for nephrotic syndrome. Biopsies revealed IgA-dominant or codominant deposits accompanied by mesangial proliferation in 14 patients (82.4%). Electron microscopy showed mesangial deposits and extensive foot process effacement (median=90%). Initial treatment consisted of corticosteroids, although many patients required additional agents to maintain remission status. Over a median follow-up of 20 months (2.2-82 months), 14 patients experienced a complete response, and 3 patients showed a partial response, with a median response time of 2 months (0.5-27 months). At least one relapse of nephrotic syndrome occurred in nine patients (53%). All patients exhibited stable or improved renal function over the follow-up period.

Conclusions: The findings in this cohort and previous studies suggest that rare cases of mild IgA nephropathy with nephrotic range proteinuria exhibit a clinical presentation, biopsy findings, treatment response, and outcome more typical of IgA nephropathy with superimposed minimal change disease. This study favors the view that such cases represent a dual glomerulopathy.

Keywords: IgA; nephrotic syndrome; renal biopsy; renal pathology.

Figure 1.

Light microscopic, immunofluorescence, and ultrastructural findings in IgA nephropathy with minimal change disease. (A) A glomerulus exhibits mesangial proliferation without evidence of endocapillary proliferation, segmental sclerosis, or crescent formation (Oxford M1, E0, and S0; hematoxylin and eosin). (B) Immunofluorescence reveals 2+ intensity staining for IgA restricted to mesangial areas. (C and D) Electron micrographs show mesangial electron dense deposits (arrows) and extensive foot process effacement. No peripheral glomerular capillary wall immune deposits are present. Original magnification, ×400 in A and B; ×8000 in C; ×10,000 in D. E0, no endocapillary proliferation; M1, more than 50% of glomeruli with at least four cells per mesangial area; S0, no segmental glomerulosclerosis.