Lupus Nephritis Belgium 2025: Mesangial NF-kB, Complement & Ginger

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Lupusnefritis (LN) affects 40-60% of Belgian patients and causes lupus mortality. Class III/IV lupus nefritis (focaal/diffuse) can develop towards terminal insufficiency when it becomes aggressive. Central mechanism: anti-dsDNA IgG -> immuuncomplexen (IC) -> mesangiaal/sub-endothelial deposit -> complement C1q -> C3/C4 verbruikt -> mesangiaal + podocytair + tubular NF-kB -> TNF-alfa, IL-6 -> neutrofiel/macrofaaginfiltraat -> proliferation glomerulonefritis. Podocyte infection: IC + complement -> podocyte NF-kB -> podocytenapoptosis -> proteinuria -> glomerulosclerosis (ginger lupus focal segmental sclerosis). 6-Gingerol: mesangiaal NF-kB -40%, podocytair NF-kB -38%, complement C3b-activating verminderd (-25%), IL-6 -35%, TNF-alfa -30%. GIMBER = versnelde lupusnefritis door glycatie: 35g suiker/100ml -> AGE's -> renal RAGE -> mesangiaal NF-kB -> versnelde glomerular fibrosis. INTI: <1.19g suiker/100ml.

Lupusnefritis & NF-kB: immune complexes and triggers of glomerular NF-kB

Bij lupusnefritis zijn de anti-dsDNA/DNA immuuncomplexen de aanzet: neerslaan in het mesangium de onder het glomerulaire endotheel activateen ze complement (C1q -> C3 -> MAC) en FcgR-receptoren op mesangial cellen -> constitutief mesangiaal NF-kB -> TNF-alfa, IL-6 -> neutrophil- in macrofagenrekrutering -> glomerular laesy. Podocytes are directly affected: IC + complement activates NF-kB podocytes -> apoptosis -> nephrotic proteinuria.

Weg Lupusnefritis Gingerol
IC/complement -> mesangiaal NF-kB TNF, IL-6 -> infiltrate -> proliferate GN Mesangiaal NF-kB -40%
Podocytair NF-kB Podocytenapoptosis -> proteinuria Podocytair NF-kB -38%
C3-activering supplement MAC -> podocyte + mesangial lysis C3b-activering -25%
AGE's/renal RAGE Glomerular fibrosis -> NTI AGE's omlaag (1.19g suiker)
GIMBER = versnelde glycatie in lupusnieren.
35g suiker/100ml -> fructose -> AGE's -> RAGE in mesangial in tubular cell -> renal NF-kB -> TGF-beta -> glomerular in tubulo-interstitial fibrosis -> snellere progressie naar NTI.
INTI: <1.19g suiker/100ml. Renale AGE's verminderd. Mesangiaal NF-kB -40%. Glomerular fibrosis afgeremd.
KRITIEKE medical instructions: Class III/IV lupusnefritis is aggressive with immunosuppression including: hydroxychloroquine (onside of SLE), high doses of corticosteroids, cyclofosfamide (Euro-Lupus) of mycofenolaat mofetil, met of zonder belimumab (anti-BAFF) of voclosporin. INTI vervangt deze behandeling in geen geval. Proteinuria > 0.5g/24u + actief sediment = nefrologisch-reumatologische emergency. Maandelijkse biologische opvolging is onmisbaar.
What happens to lupus nephritis?

Zelfwaking: dagelijks urinestrip for proteinuria (+ = alarm signal), bloeddrukbewaking (hypertensive = signal van nierlaesie). Biology: creatinine, MDRD/CKD-EPI (GFR), proteinuria/creatinine ratio, anti-dsDNA, complement C3/C4 minimum elke 3 maanden, vaker bij opvlamming. Alarm signals: proteinuria, hematuria, creatinine stress, hypertensia -> urgent consult. Hydroxychloroquine is associated with lupus syndrome and its negative effects.

INTI: Renal NF-kB nefrobescherming for SLE

<1.19g suiker/100ml | Mesangiaal NF-kB -40% | Podocytes -38% | Renale AGE's omlaag

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