International Renal Meeting and Mayo Clinic International Renal - - PowerPoint PPT Presentation

FRANCO FERRARIO FRANCO FERRARIO Nephropathology Center Nephropathology Center San Gerardo Hospital San Gerardo Hospital-

• Monza

Monza Milan Milan-

• Bicocca University

Bicocca University Italy Italy

MEMBRANOPROLIFERATIVE MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS GLOMERULONEPHRITIS

International Renal Meeting and Mayo Clinic International Renal Meeting and Mayo Clinic Day in Sardinia Day in Sardinia

April 30 April 30-

• May 3 /2011, Cagliari (Italy)

May 3 /2011, Cagliari (Italy)

MEMBRANOPROLIFERATIVE GN

• Membranoproliferative

Glomerulonephritis is a disease

• r histologic definition ?

MEMBRANOPROLIFERATIVE GN

• DEFINITION:Diffuse global

increase of tuft cellularity with diffuse thickening of the glomerular capillary wall with double contour appearance.

MEMBRANOPROLIFERATIVE GN

• Actually there are very different forms of

membranoproliferative glomerulonephritis due to very different etiologic,pathogenetic and morphogenetic mechanisms.

MEMBRANOPROLIFERATIVE GN

• SECONDARY:

Associated to monoclonal gammopathy LCDD Cryoglobulinemic GN Class IV global Lupus GN

• PRIMARY:

Type I ? Type II ? Type III ? ( variant of Type I ? ) C3-GN

We recommend judicious use of the term idiopathic MPGN because it is likely that an underlying cause can be found in almost every case of MPGN. All renal biopsies should be analyzed with anti light-chaine antibodies to detect a possible underlying monoclonal gammopathy.

• Sethi S

Clin J Am Soc Neprhol 2010

Question:how many centers performe staining with anti light- chaine antibodies by IF routine examination?

MPGN secondary to monoclonal antibody

• By Electron Microscopy the deposit were

granular and STRUCTURES were absent (Sethi 2010 ). Question: Is it EM crucial and diagnostic in differentiate MPGN secondary to monoclonal antibody with other forms of MPGN in particular LCDD( non structured granular deposits ) ?

MPGN a simple classification

PARTICIPANT CENTERS North America:

Patrick D Walker, MD, Little Rock, AR, USA Stephen M Bonsib, MD, Indianapolis, IN, USA Andrey V Cybulsky, MD, Montreal, Quebec, Canada Helen Liapis, MD, St Louis, MO, USA Neriman Gokden, MD, Little Rock, AR, USA Regina R Verani, MD, Houston, TX, USA

Europe:

Franco Ferrario, MD, Milan, Italy Laura Furci, MD, Modena, Italy Giovanni Frascà, Bologna, Italy Maurizio Manganaro, MD, Torino, Italy Giacomo Garibotto, MD, Genova, Italy Leonardo Cagnoli, MD, Rimini, Italy Alexei Sukhanov, MD, Moskow, Russia

Japan:

Kensuke Joh, MD, Chiba, Japan

Tubular basement membranes and the basement membranes of Bowman s capsule also showed similar ribbons in a segmental

• pattern. Immunofluorescence microscopy

revealed deposits of C3 in a diffuse or segmental pattern along the glomerular, tubular and Bowman s capsule basement membranes.

Histologic patterns of dense deposit disease in 67 international cases

Pattern # Pattern nome N° cases Pattern description

1 Membranoproliferative dense Tickened capillary loops and deposit disease 17 endocapillary proliferation 2 Mesangial proliferative dense Focal, segmental mensagial deposit disease 30 hypercellularity 3 Crescentic dense deposit Crescents involving > 50% of disease 12 glomeruli 4 Acute proliferative and Endocapillary proliferation with exudative dense deposit disease 8 neutrophilic infiltration

Mesangial proliferative dense deposit disease is much more common than the membranoproliferative pattern, accounting for 45% of our cases. Twenty-nine of 30 mesangial proliferative cases showed only minimal to mild proliferation, changes easily confused on light microscopy with minimal change disease.

Conclusion

DDD AND GN-C3

DDD and GN-C3 are both characterized by AP dysfunction and C3 deposits without Igs by IF. The differential diagnosis is only possible with Electron Microscopy evaluation. Question: How many centers are able to performe EM or performe EM by routine examination?

Because both GN-C3 and DDD are characterized by similar immunohistological pattern(C3 deposits) we propose that the term C3 glomerulopathy(C3G) be used to describe both DDD and GN-C3.(Sethi S Clin J Am Soc Nephrol 2010) Question:There are sufficient histological clinical,prognostic and therapeutic evidences to consider DDD and GN-C3 as part of unique category of glomerulopathy (C3G)?(Taking also into account that DDD present extremely variable morphological lesions with MP pattern in about

• nly 1/4 of cases)?