CLINICAL CASE 24, ANSWERS and SUMMARY

Name of the odd one out

Dense Deposit Disease  0%
Immunotactoid GN    66%
Familial MPGN 3      11%
C5HR5 Nephropathy  16%
C3 Glomerulonephritis  5%


Most of you got this one right. This is in light with the new and upcoming potential new classification of GNs under a C3 Glomerulopathies.  All except Immunotactoid GN is considered a C3 glomerulopathy. Immunotactoid GN would fall under a class of GN with organized deposits and under types such as fibrillary, amyloid and paraproteinemias.

I think its about time that most of us start thinking of MPGN as a pattern of injury rather than a disease till there are deposits. What the C3 glomerulopathy classification is trying to tell us is that the injury is due to the problem in the complement cascade and hence leading to different disease forms that ultimately might lead to double contouring and MPGN like lesions.
What constitutes C3 glomerulopathies: Glomerular deposits of complement C3 and absence of immunoglobulin within glomeruli or just pauci immunoglobin deposition.
Examples of these diseases are: Dense deposit disease, Idiopathic C3 glomerulopathy, MPGN type 1 with just isolated complement C3 deposits, Familial MPGN III, CFHR5 Nephropathy.


1. Idiopathic MPGN1: Usually light showing MPGN patten and immuno with IgG and C3 staining and no secondary cause identified
2. DDD: Dense deposits that are intramembranous and diffuse C3 staining and no immunoglobulin staining. associated with C3 nephritic factor problem
3. C3 Glomerulonephritis: subendothelial and mesangial deposits of just isolated C3 staining.  Possible complement dysregulation
4. Familial MPGN3: subepithelial and subendothelial deposits , linked to chromosome 1 leading to Factor H related problem
5. CFHR5 Nephropathy: Like C3 GN but have a Factor H related mutation encoded by the CFHR5 gene.

Why are these classification important: perhaps we can look for these causes in those specific cases and perhaps even help in potential donor choices for transplantation.  Medications affecting the complement system such as eczulimab might be of benefit in some of these disease entities in the near future.
If one suspects C3 glomerulopathies: its worth checking the complement cascade function: C3, C4, Factor H and I, B levels. Check also for Nephritic factor C3, Factor H antibodies, CD46 quantification.
Certain genetic mutations screenings are also available.

Below is a nice review in Nature Review Nephrology. There are nice pathology pictures and review tables.
Have a nice read.

http://www.ncbi.nlm.nih.gov/pubmed/20606628
http://www.ncbi.nlm.nih.gov/pubmed/17018561
http://www.ncbi.nlm.nih.gov/pubmed/19190809