Discussion board


Franco Ferrario MD

Renal Immunopathology Center. San Carlo Borromeo Hospital



Discussion on-line

[22:05] *** fferrario (webchat@ has joined #cin

[22:05] (gtorres> Good night, Dr Ferrario

[22:05] (MJesus> buona notte franco

[22:09] (pedro> good night Dr. Ferrario

[22:09] (fferrario> ciao from Milan in a very cold and wind nigth

[22:09] (gtorres> good night from Burgos

[22:10] (MJesus> buona notte !

[22:10] (neptuno> similar as here

[22:10] (neptuno> it is a pleasure to speak to you

[22:10] (fferrario> fortunatly there is no fog

[22:10] (neptuno> to speak to you

[22:11] (fferrario> me too

[22:12] (neptuno> would you like that the speaker starts a summary of his conference?

[22:12] (gtorres> speaker, where are you from?

[22:12] (fferrario> beeng a cold wether is no good for cryoglobulinemic patients

[22:13] (neptuno> it is true and funny comment

[22:13] (gtorres> good night

[22:14] (fferrario> neptuno is difficut to summarize the cryoglobulinemic GN

[22:14] (neptuno> well when you like, speaker, you can pass the introduction

[22:14] (speaker> could we start ?

[22:14] (neptuno> of Dr, Ferrario

[22:15] (gtorres> ok

[22:15] (neptuno> as you like an after we could ask some questions and doubts to dr Ferrario


[22:15] (speaker> Franco Ferrario. Renal Immunopathology Center- San Carlo Borromeo Hospital . Milan. Italia

[22:16] (speaker> Introduction: Cryoglobulinemic glomerulonephritis is a peculiar type of membranoproliferative glomerulonephritis almost exclusively associated with type II mixed Cryoglobulinemia, composed of monoclonal or polyclonal IgMk with rheumatoid activity against polyclonal IgG.

[22:16] (speaker> The pattern of glomerular involvement differs from that of idiopathic type I membranoproliferative glomerulonephritis and from that of the diffuse proliferative glomerulonephritis of systemic lupus eritematodes because of some characteristics:

[22:16] (speaker> a) the particularly intense infiltration of leukocytes, prevalently monocytes/macrophages (CD68 + cells), which is the major constituent of endocapillary proliferation (1,2-4)

[22:16] (speaker> b) the frequent presence, especially during episodes of acute nephritic syndrome of the so-called “intraluminal thrombi”, which are amorphous, eosinophilic, PAS positive deposits of variable size and diffusion, lying against the inner side of the glomerular capillary wall and often completely filling the capillary lumen.

[22:17] (speaker> Sometimes these huge intraluminal deposits and the subendothelial deposits are revealed by electron microscopy as having a specific microtubular structure that is identical to that of the in-vitro cryoprecipitate of the same patients. This structure consists of cylinders that are 100 to 1000 µm long and have an hollow axis, appearing in cross section like anular bodies (5-7). The identity of the deposits with the circulating IgG-IgMk cryoglobulins has been confirmed by demonstration in renal biopsy specimens of the same idiotype of the circulating monoclonal rheumatoid factor (8).

[22:17] (speaker> c) the double contoured appearance of the glomerular basement membrane which, at electron microscopy examination, appears to be due to the interposition of monocyte/macrophages between the basement membrane and the endothelial cells or the newly formed basement membrane-like material.

[22:17] (speaker> Double contours are more diffuse and evident than in idiopathic membranoproliferative

[22:17] (speaker> Mesangial sclerosis is found in late stages in the central area of the glomerular lobules (lobular glomerulonephritis) in a minority of patients. In other cases mesangial sclerosis is a late and usually mild feature.

[22:18] (speaker> In some cases, the typical pattern of cryoglobulinemic glomerulonephritis is lacking, the monocyte infiltration is less consistent, intraluminal thrombi are absent, and a picture of mild segmental mesangial proliferation is found in 20% of patients.

[22:18] (speaker> This pattern can be found at presentation of renal disease or later when a re-biopsy is performed after intensive immunosuppressive therapy.

[22:18] (speaker> Finally, about 30% of patients with cryoglobulinemic glomerulonephritis have acute vasculitis of small- and medium-size arteries, characterized by fibrinoid nerosis of the arteriolar wall and infiltration of monocytes in and around the wall (8). This renal vasculitis is often associated with other signs of systemic vasculitis, such as purpura or mesenteric vasculitis and can appear in the absence of clear glomerular involvement.

[22:18] (speaker> Even when the fibrinoid necrosis of renal arterial walls is severe, focal necrosis of the capillary loops is never present and crescentic extracapillary proliferation is a rare observation (8).


[22:19] (speaker> The multicenter retrospective study, organized by the Italian Renal Immunopathology Group, made it possible to review the histological pattern of the largest series of Cryoglobulinemic Glomerulonephritis (GN) published to date, and correlate histological features with virological, biochemical and clinical data.

[22:19] (speaker> One hundred and forty-five cases with biopsy specimens available for evaluation, including immunofluorescence analysis were recruited.

[22:20] (speaker> Morphological features: Three patterns could be clearly identified:

[22:20] (speaker> 1) Mesangial proliferative GN (10 cases, group A) characterized by mild mesangial proliferation and mesangial matrix expansion without endocapillary proliferation and exudation. The glomerular basement membranes were normal.

[22:21] (speaker> 2) Focal membranoproliferative GN (10 cases, group B) characterized by typical cryoglobulinemic lesions(mesangial proliferation, marked endocapillary proliferation and exudation, double contour appearance of glomerular basement membrane) involving only less than 50% of glomeruli, with the remnant glomeruli quite normal. In one case some endolumined thrombi were evident. Surprising mesangio-perietal deposits of IgM, IgG and C3 were present, by immunofluorescence, in all glomeruli.

[22:21] (speaker> 3) Diffuse membranoproliferative GN (108 cases, group C): The majority of patients presented the above mentioned typical features of cryoglobulinemic GN.

[22:22] (speaker> it's all for the moment

[22:22] (speaker> thanks!!

[22:22] (gtorres> some questions?

[22:22] (gtorres> What about treatment of cryoglobulinemia?

[22:22] (speaker> more about it, are at: http://www.uninet.edu/cin2001/conf/ferrario/ferrario.html

[22:23] (gtorres> please dr.ferrario

[22:23] (fferrario> i would like to stress the peculiar and diagnostic morphological features of cryo GN

[22:25] (fferrario> in particular the massive monocyte accumulation in the glomerular tuft

[22:26] (MJesus> yes, in photos of this conference, they are very apparent

[22:27] (fferrario> the role of monocyte in cryo is totally different respect ANCA-associated vasculitis

[22:27] (MJesus> how many cases of cryoglobulinemia have you seen fferrario ??

[22:28] (pedro> Do you you ever consider necessary to do renal biposy in cryo patients? or only in those with renal anomalies

[22:28] (fferrario> in a multicenter studies i personally reviewed about 200 cryo biopsies

[22:29] (MJesus> too much!!

[22:30] (fferrario> pedro-of course only in patient with renal anomalies

[22:31] (MJesus> fferrario the cylindrical structure of glomerulos, seen with electron microscopy, are patognomonic of cryoglobulinemia?

[22:33] (fferrario> good question- the cylinder are typical but more recently there is a similar disease called immunotactoid GN- with similar deposits

[22:33] (otamendi> Is CryoGN the main or the only glomerular disease induced by HCV?

[22:36] (fferrario> is not the only( for istance membranous GN) but surely the main glomerular disease due tu particular stimulation of B-lynphocytes to produce a RF IgMk

[22:36] (pedro> What is worst: to find monocytes, platelets and plasmatic cells or to find vasculitis?

[22:37] (RRobles> Do you know any report of biopsy results in cryo patients without renal signs of disease?

[22:38] (fferrario> robles-ido not know results of biopsies in patients without renal involvement

[22:40] (fferrario> pedro-it is worst to find vasculitis- the great problem of cryo patients is hypertension, probably due to sequele of vasculitis

[22:42] (pedro> Do you advice any special treatment in patients like those of your third group?

[22:44] (fferrario> in the acute phase of renal involvement the theraphy is acute theraphy with corticostheroid pulses ,cyclophosphamide and plasma exchange

[22:45] (otamendi> When must we begin antiviral therapy in severe cases?

[22:47] (fferrario> antiviral therapy is usefull in manteinance phase of disease not in acute renal involvement

[22:48] (fferrario> unfortunatly when you stop antiviral therapy you have a relapse of disease

[22:49] (pedro> In our hospital, we ask for cryo many times, but very often they are negative in spite of clinical signs of cryo diseases

[22:50] (pedro> This means that we are bad clinicians or

[22:50] (fferrario> moreover you can have severe side effects of antiviral therapy

[22:51] (pedro> that it is difficult to make the lab determination

[22:51] (fferrario> pedro- this is a great problem of good reability of laboratory

[22:53] (MJesus> do you refer to the pathologic laboratory ?

[22:54] (fferrario> surely independently of lab results the biopsy is absolutely diagnostic(in good hands)

[22:56] (pedro> but, without obtaining positive plasma cryo , Do you think we can start such agressive treatment?

[22:57] (fferrario> the problem is clinical acute renal syndrome and the results of biopsy

[22:58] (speaker> last five minutes, please, any more questions?

[22:59] (osgarur> Do you use any "particular" regimen of plasma exchange?

[23:01] (fferrario> we perform three plasma exchange a week for one month

[23:04] (pedro> how long have you had your patients on cyclosph. therapy?

[23:04] (fferrario> usually for 6 months

[23:05] (speaker> well... if there are not more question or commentary,

[23:05] (speaker> ... molte gracie Dr. Ferrario!

[23:05] (MJesus> clap clap clap clap clap clap clap clap clap
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[23:06] (pedro> thanks, Dr Ferrario, very kind of you

[23:06] (fferrario> thank you and good night

[23:06] (MJesus> are you pathologist dr. ferrario ?

[23:07] (fferrario> i am a nephologist but also a nephropatologist from 25 years

[23:08] (MJesus> very kind !!

[23:08] (MJesus> I'm pathologist only....

[23:08] (pedro> Do you look at your biopsies?

[23:09] (fferrario> i think is only important to know well renal lesions

[23:10] (fferrario> i scored in my experience about 20000 renal biopsies

[23:10] (MJesus> fiuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuu

[23:10] (pedro> so... we can send you our biopsies..

[23:11] (MJesus> 800 per year

[23:11] (MJesus> 3-4 every day ?

[23:11] (fferrario> not only in my departement but in many national and international multicenter studies

[23:12] (MJesus> do you make also, the electron microscopy of these biopsies ?

[23:13] (fferrario> pedro- if you are interested you can contact me and send your biopsies without any problem

[23:14] (pedro> thank very much,

[23:14] (fferrario> jesus-we perform EM in selected cases or for research

[23:16] (MJesus> the microscope is at Departmen of Patology? or Nephrology ?

[23:17] (pedro> well, as we have your mail, in the future, perhaps we could send you some difficult biopsie

[23:20] (speaker> ... molte gracie Dr. Ferrario!

[23:20] (fferrario> we are totally independent microscopes with electronic archive of images and a lab with immunohistochemic al, in situ hibridization and molecular biology

[23:22] (MJesus> and the pathologist are agree ?

[23:23] (fferrario> they well cooperate with me

[23:23] (MJesus> very nice of all you

[23:24] (fferrario> but they are general pathologist not very expert in renal diseases

[23:24] (MJesus> :(((

[23:25] (MJesus> I think, reanl biopsies are the most beautifull biopsies

[23:25] (fferrario> i agree with you

[23:26] (MJesus> :)) It is my subspeciality

[23:26] (MJesus> mi tesis was over nephronoptisys

[23:26] (fferrario> renal pathology is a very interesting and large field

[23:28] (MJesus> you are right

[23:28] (MJesus> have you seen the conferences of hoffman ?

[23:28] (fferrario> i prefer nephritis with all new incredible knowledges of immunological and cell involvement in renal damage

[23:29] (fferrario> yes

[23:31] (pedro> thanks to everybody and in particular to Dr. Ferrario

[23:32] (pedro> we are very grateful to you

[23:32] (MJesus> clap clap clap clap clap clap clap clap clap
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[23:32] (fferrario> dear maria thank you for this exciting conference and i hope to meet you personally ciao

[23:32] (pedro> thanks

[23:32] (pedro> we hope so

[23:33] (pedro> by, by

[23:33] (MJesus> I hope to know your as soon as possible !

[23:34] (pedro> adios, hasta mañana

[23:34] (fferrario> adios

[23:34] (MJesus> adios pedro

[23:34] (pedro> gracias, Dr Ferrario

[23:34] (pedro> adios y buenas noches

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[23:35] *** fferrario has quit IRC (Leaving)

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