A continuation of my autoimmune renal biopsy week on service.... A case of lupus vasculopathy with prominent arteriolar immune complex deposits visible by IF, LM, EM....

Lupus vasculopathy: under recognized. Large vessels with Ig deposits & no inflammation. Bx: thick vessel walls with accumulation of IgG & C3. No arteritis. Dx: 1) ATN 2) Lupus vaculopathy 3) Mesangial lupus nephritis (class II) 35 yr with lupus & rise in S Cr to 2.5 from 1.2.

Chunky lupus vasculopathy. Massive luminal immune complexes in arteriolar lumens. Showed full house IF staining (IgG pictured). Superimposed acute TMA as well. Class IV LN in gloms. #renalpath #pathtwitter

Anthony Chang, MD (張賀文) This is why it is so important discussing each biopsy with the clinical team and providing a good narrative micro summary in the report as the artificial bins of banff don't always capture the continum of rejection morphology. Especially in edge cases.

I Retrograde reflux of tubular epithelium into the glomerular urinary space would be a more correct description of what is happening

Nice pictures. Arteriolar CNI toxicity is often overdiagnosed: differential of hypertension, diabetes and donor disease must be kept in mind. Over-diagnosis can be seen even in leading journal publications such as those in NEJM GlomCon IAP Central TTS Indian Society of Renal& Transplantation Pathology

Nice case; JCV nephropathy indeed the most likely diagnosis but must confirm by PCR to rule out mutant BK virus not reacting to your antibody or PCR primers. Rarely, monkey SV40 and other human viruses can be similar. After all, a viral inclusion is just an aggregate of virions

Nice pictures; You can see this change in non-transplant biopsies and in biopsies of patients on CNI free regimens. Keep osmotic injuries in the differential: including mannitol, 12.5% glucose saline, radiocontrast media, IVIG, Remedesivir etc.

Nice illustration of a lesion that can be used to diagnose CNI toxicity, keeping in mind that the pathogenesis in some cases simply reflects arteriolar narrowing. Diabetes and hypertension can cause similar lesions in native kidneys & in transplanted patients not receiving CNIs.

In the transplant world (liver or kidney) IgG4 rich infiltrates are most often plasma cell rich T-cell or antibody rejection. Rarely they can be recurrent or denovo IgG4 disease or a PTLD

Bottomline: Molecular Dx is not useful if MVI is absent. Its value in DSA-, C4d- MVI is also limited, since it tends to call ABMR, without regard to non-ABMR causes of MVI, [TCMR-PTC, BKVN, GN, plasma cell rich, NK missing self, macrophages, innate immunity]

Assuming Congo red negative: I suspect it is one of the ~ 30’collagen types that have been defined by proteomics. Some Are known to occur in basement membranes

Many mechanisms talked about but all are amplified or actually initiated by T-cells IHC always shows numerous CD3 cells and argues for T-cell therapy. I have seen many case respond to steroids.

Antigen presenting cells are expected in all immune infiltration including interstitial nephritis. But If Langerin cells occur in clusters think of histiocytosis X

Counter argument. If Malignant hypertension can cause severe kidney injury (flea bitten kidney), lower BP cannot be completely harmless. GlomCon NDT AJKD Int Society of Nephrology JASN_News

#ABMR My view of antibody mediated rejection in the liver nejm.org/doi/full/10.10… GlomCon American Journal of Transplantation The Tell Show Renal Pathology Society ASN Publications NDT

Boonyarit Cheunsuchon, MD Some recommend congo red staining on all light chain cast nephropathy cases as intra tubular amyloid occurs in a significant # of cases and is associated with development of systemic amyloidosis: pubmed.ncbi.nlm.nih.gov/29052601/

Nice article. Articles using arteriolar hyaline change alone as diagnostic criterion for CNI toxicity have appeared in major journals like NewEngJMed and caused a lot of confusion in the field. Hypertension, diabetes, and age alone are important in differential diagnosis.

Indicative of ANA which can occur in many conditions other than lupus

Here is one possible sequence: TCMR->new antigens released->antibodies are forming. Need follow up to see if C4d positivity and microvascular inflammation, though DSAs can also be transient.