Professor, Mayo Clinic, MN. šÆrenal pathology. Use X to teach, clinical info changed. Be kind to animals. Love dogs. Views are mine. Comfortably numb.
Minnesota, USA
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Sanjeev Sethi retweeted
KIDNEY WEEK 2026: In IgA nephropathy, proteomics reveals glomerular IgA1/IgA2 and IgG1 deposits, with predominant activation of the alternative and terminal complement pathways.
Cara et al. Kidney Int. 2026.
doi.org/10.1016/j.kint.2026.ā¦
#IgAN
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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 doesnāt 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/artā¦
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Sanjeev Sethi retweeted
Characterization of IgA, IgA immune complexes and complement depositions in IgA nephropathy using laser microdissection and mass spectrometry
@AnilaCara @GianMarcoB65728 @mvargas07 @ilariokidn @fervenzaf @SethiRenalPath @Kidney_Int
kidney-international.org/artā¦
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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.
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Sanjeev Sethi retweeted
Superimposed FSGS worsens Kidney Prognosis in DN ā¼ļø Risk factor for progression, the clue by š« biopsy. @SethiRenalPath @mvargas07 @mimamed @Daniela95926028 @martacasalmoura @boulboulasana
ovid.com/10.34067/KID.000000ā¦
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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 Bowmanās 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.
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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-ā¦
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.
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Much needed test.
Quantitative serological detection of NELL1 autoantibodies in membranous nephropathy - Kidney International kidney-international.org/artā¦
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The simple concept was to correlate hemoglobinuria with active inflammation in IgA nephropathy. This large study confirmed the concept. Thanks for including me.
A multi-center cohort study evaluated hemoglobinuria as a marker of inflammation in IgA nephropathy - Kidney International kidney-international.org/artā¦
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Sanjeev Sethi retweeted
A benchmark study on dipstick hemoglobinuria as a better marker for inflammation in IgAN. Validating itās use in clinical trials.
A multi-center cohort study evaluated hemoglobinuria as a marker of inflammation in IgA nephropathy - Kidney International kidney-international.org/artā¦
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Explosionš„- A glomerulus on fire š„.
Light microscopy- Fibrinoid necrosis in the middle of capillary tufts rupturing the glomerular capillary walls (blowing up the tufts), with massive efflux of RBCs into Bowmanās space.
Dx: Necrotizing glomerulonephritis, associated with MPO/pANCA vasculitis (hydralazine/clinical)
Note many uninvolved glomeruli. Only severe systemic disease with focal involvement on LM. š¤
50 yr old with AKI, āpANCA/MPO. History of hydralazine use.
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Sanjeev Sethi retweeted
Interested in pursuing a career in renal pathology? Applications are opening for the upcoming academic year 2027-2028 for a Renal Pathology Fellowship at Mayo Clinic.
An excellent opportunity for advanced training in medical renal pathology, with exposure to a broad spectrum of complex cases, multidisciplinary collaboration, research, and education.
If youāre considering applying, feel free to reach out for more information. college.mayo.edu/academics/rā¦ @MPAlexanderMD
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Long day of weekend cases today:
1. Necrotizing and crescentic glomerulonephritis, Hydralazine-associated MPO/pANCA
2. Acute interstitial nephritis
3. IgA nephropathy, Crohns disease associated
4. ATN/diabetes
5. Transplant with perivenular inflammation
6. Myeloma kidney
7. Necrotizing arteritis, MPO-associated
8. FSGS (obesity), transplant glomerulopathy
9. Protocol bx: normal
10. IgA nephropathy, very active, M1E1S0TOC1
11. IgA, with chronic changes M1E0S0T1C0
12. GBM abnormalities? in patient with hematuria.
And nephrectomy from life source for transplant.
Thank you @AnilaCara for sitting with me and going through the cases.
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Mimic:
IgA Nephropathy can mimic immune complex (IC)-MPGN.
LM: Membranoproliferative (MPGN) pattern
Routine IF: inconclusive
Pronase IF: mesangial IgA 2+
EM: mesangial deposits
Dx: IgA nephropathy M1 E1 S0 T0 C0
Case was labeled primary IC-MPGN
50-yr old with hematuria and proteinuria. Serology negative.
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Truly honored and privileged to present the Helmut Rennke lectureship at GlomCon Hawaii.
A Mentor, a Teacher can change the life of a student and I owe a debt of gratitude to Dr. Rennke for what I have learned and achieved.
I spoke on MPGN, the journey, and how it has changed from a pattern based diagnosis to an etiology based diagnosis and its impact on patient care and management.
@GlomCon @MayoClinicNeph @MayoClinicPath
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Sanjeev Sethi retweeted
Another one of my favorite papers: chronic post-infectious GN (PIGN) is often a complement dysregulation disorder. Often triggered (second hit) by an infection making it appear as a PIGN. Humps also can mislead. @SethiRenalPath #GlomConHawaii
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Sanjeev Sethi retweeted
Few papers (schemes) have impacted GN clinicopathology more than this. A true paradigm shift of seismic proportion. MPGN classification for the masses. #GlomConHawaii @SethiRenalPath
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Unexpected in a 89 yr old man, but got the diagnosis on initial look.
-Severe interstitial nephritis
-Lots of plasma cells
-Small granulomas
-Back ground of fibrosis, can be storiform
-Cells stain for IgG4 (> 10 IgG4 cells/high power)
Diagnosis: IgG4-related kidney disease.
89 yr old with acute on chronic kidney disease. + atypical ANCA. S Creatinine 3.0. COPD, GERD, CVA.
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