Clinicopathological analysis of IgA nephropathy combined with other glomerular diseases

Abstract

It is not rare to find Immunoglobulin A (IgA) nephropathy (IgAN) combined with other glomerular diseases, which can be called compound IgAN (cIgAN). Till now, clinical-pathological investigation of cIgAN was lacking, especially the severity of "background IgAN lesions." This research aimed to investigate the incidence, clinical and pathological characteristics of cIgAN, and thus improve the understanding of the clinical significance of this combination.Patients with cIgAN diagnosed in Peking University People's Hospital from November 2012 to April 2018 were retrospectively analyzed. Patients with IgAN without compound glomerular diseases (sIgAN) were enrolled as a control group.Among 1407 patients diagnosed with IgAN, 80 (5.69%) were cIgAN patients. Compared with sIgAN, cIgAN patients had a significantly lower prevalence of microscopic hematuria and more urine protein. There were 10 pathological types of glomerular diseases combined with IgAN, led by diabetic nephropathy 37 (46.25%) and membranous nephropathy 14 (17.5%). Histologically, although the mesangial hypercellularity was comparable in 2 groups, cIgAN patients had a lower prevalence of endocapillary proliferation, segmental glomerulosclerosis, and cellular or fibrocellular crescents formation, as well as weaker immunofluorescence intensity for IgA and C3 (all P < .05). Eight out of 27 (29.63%) cIgAN patients with follow-up data (5-48 months) developed irreversible end-stage renal disease requiring dialysis.The order of incidence of concomitant diseases was similar to that of the pure diseases. The "background IgAN associated lesions" except mesangial hypercellularity were relatively mild in cIgAN group. Those might suggest that in some cases, IgAN seems to be a chance finding, and the combined diseases may play a more important role in the clinicopathological features of the patients than the nephritis caused by IgA deposition. While diagnosing IgAN, other combined glomerular diseases need to be carefully considered by nephrologists and pathologists.

Figure 1

Representative immunofluorescence, light microscopy, and electron microscopy on biopsy specimen from cIgAN patients combined with diabetic nephropathy (A–D) and membranous nephropathy (E–H). (A and E) Immunofluorescence reveals mesangial staining for IgA (200×). (B) Immunofluorescence reveals linear GBM and tubular basement membrane staining for IgG (200×). (C) Masson trichrome stain shows mild (the left glomerular) to moderate (the right glomerular) mesangial hypercellularity (200×). (D) Electron microscopy shows diffuse thickening of glomerular basement membrane and increased mesangial matrix. The electron dense deposits can be seen in the mesangial region, with diffuse podocyte foot-process effacement (4200×). (F) Immunofluorescence reveals fine granular GBM staining for IgG (200×). (G) Masson trichrome stain shows thickened GBMs and mild mesangial hypercellularity (200×). (H) Electron microscopy shows GBM thickening, with electron dense deposits in the subepithelial region (white arrow) and mesangial region (black arrow), and with diffuse podocyte foot-process effacement (4200×). cIgAN = compound IgA nephropathy, GBM = glomerular basement membrane.