RENAL PATHOLOGY LEARNING

IgA Nephropathy

by

Franco Ferrario and Maria Pia Rastaldi

Dr Franco Ferrario
Renal Immunopathology Center
San Carlo Borromeo Hospital
Milano, Italy

The characteristic and diagnostic lesion of idiopathic IgA nephropathy (IgA GN, Berger's disease) is represented by glomerular deposition of IgA, as a unique or predominant positive immunoglobulin. Despite the relatively uniform aspect of the immunohistological pattern, the morphological lesions observed by light microscopy are extremely variable. This variability of glomerular and interstitial alterations has frequently created some difficulties in histological classification.

Glomeruli can show very mild lesions, without mesangial matrix expansion or mesangial cell proliferation.

In other cases, mesangial matrix enlargement is conspicuous and predominates over a relatively mild mesangial cell proliferation.

Most cases are characterized by focal and segmental mesangial proliferation (Fig. 1).

 

Figure 1

 

In approximately 20% of cases, mesangial matrix expansion and mesangial cell proliferation are particularly severe, with a morphological pattern that looks like idiopathic m embranoproliferative glomerulonephritis.

Independent of the entity of mesangial damage, the presence of a necrotizing lesion has been described by many authors. The segmental tuft necrosis can be the only lesion highlighted, possible expression of an early phase of capillary damage.

In most cases, the necrotic lesion is associated with an area of cellular extracapillary proliferation.

By silver staining the necrotic damage is clearly evident, with segmental destruction of the glomerular basement membrane and associated extracapillary reaction (Fig. 2).

Figure 2

By monoclonal antibodies directed against leukocytes it has been possible to demonstrate the predominant presence of monocyte-macrophages (CD68), both in the areas of necrosis and in the segmental extracapillary reaction.

In these necrotizing extracapillary forms, it is very common to find interstitial infiltrates with predominant periglomerular localization, adjacent to the areas of intraglomerular lesions.

By silver staining a possible rupture of the Bowmans capsule is clearly demonstrated, making it difficult to discriminate between intra and extraglomerular lesions (Fig. 3).

Figure 3

In our opinion, all these “active lesions” can play an important role in the progression of IgA GN, due to possible progressive “poussées” of necrotizing extracapillary damage, with consequent formation of glomerular sclerosis. The glomerular sclerotic lesions, characterized by well defined rounded areas of segmental sclerosis, represent a final reparative stage of the necrotic damage, as demonstrated in repeat biopsies (Fig. 4).

Figure 4

For this reason, many researchers believe that these forms should be treated with steroids and cyclophosphamide pulses.

In rare cases it is possible to find a diffuse extracapillary glomerulonephritis with circumferential cellular crescents in more than 60-70% of glomeruli, clinically characterized by rapidly progressive renal failure.

Marker of poor prognosis, diffuse interstitial infiltrates are commonly found in IgA GN.

Though the diagnostic “marker” of IgA GN is represented by a predominant glomerular deposition of IgA, the immunohistological pattern is variable.

An intense IgA deposition in the mesangial stalk is more common pattern (Fig. 5).

Figure 5

A mesangio-parietal pattern is also frequently observed. The parietal deposition of IgA has been associated to a worse prognosis.

By electron microscopy mesangial electron dense deposits are found in all glomeruli associated with mesangial cells proliferation (Fig. 6).

 

Figure 6

 

Questions

 

REFERENCES
  
1. Ferrario F, Rastaldi MP. Histopathological atlas of renal diseases- IgA nephropathy. J Nephrol 2004 May-Jun; 17(3):351-353.
2. Schena FP, Gesualdo L. Markers of progression in IgA nephropathy. J Nephrol 2001 Nov-Dec;14(6):554-574.
3. Mustonen J, Syrjanen J, Rantala I, Pasternak A. Clinical course and treatment of IgA nephropathy. J Nephrol 2001 Nov-Dec;14(6):440-446.
4. Ballardie FW. IgA nephropathy treatment 25 years on: can we halt progression? The evidence base. Nephrol Dial Transplant 2004; 19:1041-1046.
5. Geddes CC, Rauta V, Gronhagen-Riska C, Bartosik LP, Jardine AG, Ibels LS, Pei Y, Cattran DC. A tricontinental view of IgA nephropathy. Nephrol Dial Transplant 2003; 18:1541-1548.
6. Tumlin JA, Lohavichan V, Hennigar R. Crescentic, proliferative IgA nephropathy: clinical and histological response to methylprednisolone and intravenous cyclophosphamide. Nephrol Dial Transplant 2003; 18:1321-1329.
7. D'Amico G. Natural history of idiopathic IgA nephropathy and factors predictive of disease outcome. Semin Nephrol 2004 May;24(3):179-196.
8. Tumlin JA, Hennigar RA. Clinical presentation, natural history, and treatment of crescentic proliferative IgA nephropathy. Semin Nephrol 2004 May;24(3):256-268.
9. D'Amico G, Napodano P, Ferrario F, Rastaldi MP, Arrigo G. Idiopathic IgA nephropathy with segmental necrotizing lesions of the capillary wall. Kidney Int 2001 Feb;59(2):682-692.
10. Bartosik LP, Lajoie G, Sugar L, Cattran DC. Predicting progression in IgA nephropathy. Am J Kidney Dis 2001 Oct;38(4):728-735.
11. Haas M. Histologic subclassification of IgA nephropathy: A clinicopathologic study of 244 cases. Am J Kidney Dis 1997;29:829-842.
12. Ferrario F, Rastaldi MP, Napodano P. Morphological features in IgA nephropathy. Ann Med Interne (Paris) 1999 Feb;150(2):108-116.