Sanjeev Sethi

Another new one for me.
Young body builder with large muscle mass and supplement use.

Kidney Biopsy:
Focal and segmental glomerulosclerosis (FSGS)
+
Many platelet thrombi within glomerular capillary loops, rupturing the capillary walls and extending into Bowman’s space. (Best seen on electron microscopy)

Thrombi = likely related to supplements.

This is a 24-year-old man presenting with rise in creatinine (1.8) and minimal proteinuria.

Complete summary and more of IgA nephropathy using mass spectrometry.

1. Majority of IgA is IgA1.
2. Smaller amounts of IgA2 are also present.
3. Both IgA1 and IgA2 colocalize with IgG, showing that the deposits are composed of IgA1/IgG and IgA2/IgG.
4. Dominant IgG subclass is IgG1.
5. J chain that binds monomers of IgA into dimers is present in majority of cases, indicating that the IgA is mucosal derived (as circulating IgA is monomer and doesn’t have J chain)
6. Absence of PIGR indicates that IgA is not derived from secretions such as saliva, tears, etc. PIGR is a peptide in IgA (present in secretions), that prevent the breakdown of IgA by bacteria.

Taken together: IgA immune complexes in IgA nephropathy are made up of antigenic (galactose-deficient) mucosal-derived IgA and IgG.

7. Complement: Large amounts of C3 and C9 indicating alternative and terminal pathways of complement activation.
8. Minimal classical/no lectin pathway proteins.
9. Some correlation with MESTC score but bottom line= all IgA nephropathy shows lots of C3 and C9.
10. Abundant CFHR5 indicating that there is breakdown of C3 into inactive C3=iC3b.
11. Complement is a major player in the inflammatory process in IgA nephropathy.

kidney-international.org/article/S0085-…

Kidney biopsy findings in a patient treated with complement inhibitor-pegcetacoplan. First one for me.

Glomeruli appear and vacuolated and washed out. The vacuoles are most prominent in the podocytes.

The interstitium also contains vacuolated cells.

Glomeruli appear non proliferative and were negative for Ig and C3 on Immunofluorescence.

However, there was extensive global glomerulosclerosis and tubular atrophy and interstitial fibrosis.

Tough case.

LM: granulomatous interstitial nephritis, extensive.
IF: negative.

Look carefully and you start seeing small foci of necrosis in glomeruli, surrounded by inflammation/rupture of Bowman’s capsule.

Dx: 1. Granulomatous interstitial nephritis. 2. Necrotizing glomerulonephritis, pauci-immune. (both possibly drug related).

30-yr woman with rash, serum creatinine 10, bipolar disorder-just started treatment. ANCA, other serology negative.

Membranous nephropathy in the allograft kidney.

Contactin 1 (CNTN1) was detected using mass spectrometry.

Evaluation revealed long history of chronic demyelinating polyneuropathy.

De Novo Contactin-1- associated Membranous Nephropathy in Kidney Allograft. - Kidney International Reports kireports.org/article/S2468-…

Teaching points-
1. CNTN1-associated MN is rare type of MN associated with chronic inflammatory demyelinating polyneuropathy.
2. CNTN1-associated MN can occur in the allograft many years after the transplant.
3. Clinical and laboratory evaluation in such cases will reveal a chronic inflammatory demyelinating polyneuropathy, although the disease may be clinically quiescent.
4. Laser microdissection and mass spectrometry is a useful methodology for detection of MN antigens.