IgA-dominant postinfectious glomerulonephritis: a report of 13 cases with common ultrastructural features

Summary

A unique form of postinfectious glomerulonephritis characterized by IgA-dominant immune complex deposits was recently described by Nasr et al (Hum Pathol. 2003;34:1235-1241), each case after a Staphylococcus infection in diabetic patients. Others have described glomerulonephritis with IgA-containing immune complex deposits in association with staphylococcal infections, although their histology was more varied and electron microscopy often did not to show large subepithelial deposits (“humps”) typical of postinfectious glomerulonephritis. In this report, we describe demographic, clinical, and renal biopsy findings in 13 cases of IgA-dominant postinfectious glomerulonephritis, each characterized by subepithelial humps at various stages of resolution. All patients presented with renal insufficiency (mean serum creatinine ± SD, 4.4 ± 2.7 mg/dL), hematuria (macroscopic in 3), and proteinuria (nephrotic range in 6). Based on histology and electron microscopy, postinfectious glomerulonephritis was classified as acute in 2 patients, subacute in 3, and resolving/persistent in 8. There were 6 patients who had recent Staphylococcus aureus infections (3 methicillin resistant), 5 who were diabetic, and 3 with nephropathy. A total of 4 patients (3 with serum creatinine >8.0 mg/dL at biopsy) developed end-stage renal disease, whereas 9 had a mean serum creatinine of 2.0 ± 1.1 mg/dL (range, 0.8-4.4) at 10 ± 13 months (range, 2-44) after biopsy. In summary, IgA-dominant postinfectious glomerulonephritis resembles poststreptococcal glomerulonephritis in its histologic spectrum and electron microscopy findings, is often associated with staphylococcal infections, occurs in diabetics and nondiabetics, and may resolve if renal failure at presentation is not severe.

Introduction

Postinfectious glomerulonephritis (PIGN) is an immune complex-mediated form of glomerulonephritis (GN) most often associated with group A streptococcal infections, although other organisms may produce a similar clinical and morphologic picture [1]. In poststreptococcal GN, the glomerular immune complex deposits are composed mainly of IgG and complement, with C3 persisting longer than IgG in the resolving phase of the disease [1], [2], [3]. Recently, however, Nasr et al [4] reported 5 cases of acute PIGN characterized by glomerular deposits containing IgA as the dominant immunoglobulin; each occurred after a staphylococcal infection (3 methicillin-sensitive Staphylococcus aureus [MSSA], 2 Staphylococcus epidermidis) in patients with underlying diabetic nephropathy.

There have been other reports [5], [6], [7], [8] of GN with IgA-containing immune complex deposits in association with staphylococcal infections, although the pathologic features of these cases are quite variable. Spector et al [5] reported 2 cases of mesangial proliferative GN with deposits of IgA, IgG, and C3 in the setting of S aureus infections. They also reported 1 additional case of diffuse proliferative GN with features of acute PIGN at autopsy after an S aureus infection, although immunofluorescence (IF) studies were not done in the latter case. Koyama et al [6] reported 10 cases of GN after methicillin-resistant S aureus (MRSA) infections. A renal biopsy was done in 6 of these cases, showing variable histology ranging from mild mesangial proliferative GN to diffuse mesangiocapillary GN with crescents. IF showed mesangial and capillary wall staining for IgA and IgG (usually codominant) as well as for C3; however, no electron microscopy (EM) was done. These workers later developed a monoclonal antibody against an S aureus cell membrane protein (“probable adhesin”), and by immunohistochemistry identified this protein in glomeruli from 3 of 4 renal biopsies with post-MRSA GN and 85 (67%) of 126 biopsies showing IgA nephropathy or Henoch-Schonlein purpura nephritis, but in only 1 of 65 biopsies with glomerular diseases not showing IgA-containing immune deposits [7]. More recently, Satoskar et al [8] reported 8 patients with IgA-dominant or codominant immune complex GN and underlying staphylococcal infections (5 MRSA, 2 MSSA, 1 S epidermidis). All presented with acute renal failure, active urine sediment, and proteinuria; 2 were diabetic with nephropathy. However, renal biopsies of 6 of these patients showed exclusively or predominantly mesangial proliferative GN, and 2 others had features of cryoglobulinemic GN, whereas none showed subepithelial “humps” typical of PIGN by EM [8]. As in the series of Nasr et al [4], in which 4 of 5 patients developed end-stage renal disease (ESRD), there was a high rate of ESRD (5/8, 63%) among the patients reported by Satoskar et al [8].

Nevertheless, it should be emphasized that unlike the patients reported by Nasr et al [4], all of whom had biopsy findings of acute PIGN, most of the remaining cases of GN with IgA deposits associated with staphylococcal infections appear to lack typical histologic and/or ultrastructural features of PIGN [5], [6], [8]. It is therefore possible that these latter cases represent other forms of GN, such as secondary IgA nephropathy and cryoglobulinemic GN. As such, to determine the frequency of IgA-dominant PIGN, its clinical features including association with staphylococcal infections and underlying diabetes and frequency of progression to ESRD, and its pathologic spectrum on renal biopsy, we retrospectively reviewed our renal biopsy records for the past 4 years to identify cases of immune complex GN with IgA predominance and ultrastructural features typical of PIGN.