Fig. 1

Light and electron microscopic images of 6 successive renal biopsies compared with various therapies. (1A-C) Initial biopsy with immune complex immunofluorescence pattern showing severe glomerular endocapillary proliferation and leukocyte exudation (a – H&E), glomerular basement membrane double contours (b – methenamine silver), prevailing transmembranous and scattered hump-shaped deposits (C – electron micrograph). (2A-C) On conventional immunosuppressive therapy in the second biopsy with highly dominant C3 immunofluorescence, severe glomerular proliferation, leukocyte exudation with pronounced lobularity (a – H&E), extensive capillary wall mesangial interposition with glomerular basement membrane double contours and disruption (b – methenamine silver), evidenced also on electron micrograph (c). (3A-C) On rituximab and plasmapheresis in the third biopsy, only slightly less active C3 membranoproliferative glomerulonephritis type III of Anders and Strife but significantly increased interstitial fibrosis with tubular fatty degeneration and cholesterol crystalline clefts, fibrocellular crescents and glomerulosclerosis (a – H&E, B – methenamine silver, c – electron micrograph). (4A-C) After initiation of eculizumab, while interstitial fibrosis, focal segmental glomerulosclerosis (a – AFOG trichrome) and mesangial-transmembranous deposits persist, a significant decrease in glomerular hypercellularity, active crescents and disappearance of leukocyte infiltration and necrotizing lesions are visible on methenamine silver stained section (b) and electron micrograph (c). (5A-B) With ongoing eculizumab therapy but withdrawal of conventional immunosuppression associated with the reappearance of immune complex immunofluorescence, similar histopathology as in the fourth biopsy (a – AFOG trichrome) but more pronounced refractile red stained glomerular capillary wall and mesangial deposits share some similarities to those of dense deposit disease (b – AFOG trichrome) and on the inner aspect of transmembranous deposits interrupting powdery dense deposits ascribed to eculizumab binding are visible on electron micrograph (c). (6A-C) After ongoing eculizumab and methyprednisolone therapy, chronic C3 glomerulonephritis presents similarly as in the fifth biopsy, with significant focal segmental glomerulosclerosis and interstitial fibrosis (a – AFOG trichrome), a lower level of glomerular proliferation and absence of active glomerular inflammation (b – AFOG trichrome) but with continuous powdery electron dense deposits (c – electron micrograph)