Classification of Membranoproliferative Glomerulonephritis (MPGN)

00:00 Current day classification.

00:02 First, immunofluorescence microscopy. You know what that means.

00:07 Immunofluorescence is literally looking for immunoglobulins.

00:11 Let’s first take a look at the arm on your left, shaded light gray, where we find immunofluorescence shows immunoglobulin Ig plus C3 deposits in the capillary wall plus the mesangium.

00:25 Now, you’re anatomically or you’re thinking and seeing all this at this juncture.

00:29 Next, this is immune-complex mediated MPGN.

00:33 Membranoproliferative glomerulonephritis, stop there.

00:36 Immune-complex mediated. What does that mean to you? It will be a type III type of hypersensitivy.

00:42 This would be the most common type MPGN etiology that we’ll take a look at in general.

00:49 Next, well, we'll take a look at to determine the source of the circulating immunoglobulin or immune complexes.

00:56 By that I mean, that immune complex that's being deposit now as a whole, as I said, this will be the most common etiology.

01:02 And you’ll see the differentials upcoming.

01:05 To determine the source, maybe it was an infection.

01:08 The big infection that you wanna keep in mind here is Hepatitis C.

01:14 What others? Well, the other ones, we have autoimmune diseases including rheumatologic diseases and this...

01:20 that will include things like Sjogren rheumatoid arthritis, Scleroderma, SLE, and so forth.

01:27 What else may have immune-complex deposition? Monoclonal gammopathies or dysproteinemias.

01:35 Big example here will be monoclonal gammopathy of undetermined significance and multi-myeloma.

01:42 Or something like Waldenstrom macroglobulinemia.

01:45 This is our first category of MPGN, it’s immune-complex mediated.

01:50 Next, what if the immunofluorescence shows dominant C3 staining with little or no C1q? That then brings us to our branch on the right.

02:03 This will be complement-mediated MPGN.

02:07 Complement-mediated. Stop there.

02:09 Take a look at the two major classifications.

02:12 We have immune-complex and we have complement-mediated.

02:16 If it is complement-mediated then your next step of management or at least your next step at diagnosis would be in fact your electron microscopy.

02:23 Now, what's this electron microscopy? If you find that your entire basement membrane is black and thick, thick and black, a rare, but you still need to know it big time, then it’s DDD.

02:37 That triple D stands for dense deposit disease.

02:42 Once again, dense deposit disease.

02:45 Where? On the basement membrane, it's black and thick.

02:48 This is your electron microscopy.

02:51 Whereas, well, you can have issues with what's known as C3 glomerulonephritis, as well.

02:57 A separate issue. We’re not gonna spend a lot of time there.

03:00 But we will spend time with type II MPGN.

03:04 Listen, type II MPGN, is only associated with dense deposit disease.

03:11 Is that clear? Let me ask you something else.

03:13 Well, let me finish this up then I’ll ask you, of the two, immune-complex or complement-mediated, which one of these would be more common in terms of occurrence? And you’ll see what I'm getting to.

03:26 Dysregulation of alternative complement pathway, the alternative complement pathway.

03:33 So what do you end up having? Is the fact that you have antibodies to complement regulators.

03:39 These are the important points that you wanna take away from this flow chart to give yourself a bird’s eye view how to approach your patient with MPGN and then as we go further through here we’re gonna plug-in the details.

03:49 Let us now continue.