Kidney in Systemic Diseases

Kidney in Systemic Diseases

Kidney in Systemic Diseases

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Diabetic Nephropathy - Sweet Kidney Sorrow

  • Pathogenesis: Non-enzymatic glycosylation (AGEs), PKC activation, hemodynamic changes (glomerular hyperfiltration), sorbitol pathway flux → all cause glomerular damage.
  • Morphology:
    • GBM thickening
    • Diffuse mesangial sclerosis
    • Nodular glomerulosclerosis (Kimmelstiel-Wilson lesions) Diabetic nephropathy vs amyloidosis histology
    • Hyaline arteriolosclerosis (afferent & efferent arterioles)
  • Stages (Mogensen) & Clinical Features:
> ⭐ Kimmelstiel-Wilson nodules (nodular glomerulosclerosis) are pathognomonic for diabetic nephropathy.

Lupus Nephritis - Wolf's Kidney Attack

Pathogenesis: Type III Hypersensitivity; DNA/anti-DNA immune complex deposition.

ISN/RPS Classification (2003/2018): 📌 (I-VI)

ClassNameKey Feature
IMinimal Mesangial LNNormal LM, mesangial IC
IIMesangial Proliferative LNMesangial hypercellularity
IIIFocal LN<50% glomeruli affected
IVDiffuse LN≥50% glomeruli (S/G)
VMembranous LNSubepithelial deposits
VIAdvanced Sclerosing LN>90% sclerosed glomeruli
  • IF: "Full house" pattern (IgG, IgA, IgM, C3, C1q). Lupus Nephritis Immunofluorescence "Full House" Pattern
  • EM: Subendothelial, mesangial, subepithelial deposits.
  • LM: Wire loop lesions, hyaline thrombi, endocapillary proliferation, crescents.

Clinical: Varies by class; hematuria, proteinuria, nephrotic/nephritic syndrome, HTN, renal insufficiency.

⭐ "Full house" immunofluorescence (co-deposition of IgG, IgA, IgM, C3, and C1q) is highly characteristic of lupus nephritis.

Renal Vasculitis - Vessel Villainy

ANCA-Associated Vasculitis (AAV) comprises systemic necrotizing vasculitides targeting small vessels, frequently causing severe renal injury.

  • Primary Renal Lesion: Pauci-immune crescentic glomerulonephritis (GN) - minimal immune deposits on IF/EM.
  • Presentation: Rapidly Progressive GN (RPGN), hematuria, non-nephrotic proteinuria, systemic symptoms (fever, weight loss, arthralgia).
AAV TypeANCA ProfileDistinguishing Systemic Involvement
GPA (Granulomatosis with Polyangiitis)c-ANCA (anti-PR3)Upper/lower respiratory tract (granulomas), sinusitis, renal
MPA (Microscopic Polyangiitis)p-ANCA (anti-MPO)Kidneys, lungs (capillaritis); no granulomas
EGPA (Eosinophilic GPA)p-ANCA (anti-MPO)Asthma, significant eosinophilia, neuropathy, cardiac involvement

Histopathology of Glomerulonephritis

Renal Amyloidosis - Congo Red Kidneys

  • Definition: Extracellular deposition of misfolded proteins (insoluble fibrils).
  • Types:
    TypePrecursor ProteinAssociations
    ALIg light chainsPlasma cell dyscrasias (e.g., MM)
    AASerum Amyloid A (SAA)Chronic inflammation (e.g., RA, IBD)
  • Renal Morphology:
    • Glomeruli: Most common. Amorphous, eosinophilic deposits (mesangium & capillary walls).
    • Congo Red: Salmon-pink; apple-green birefringence (polarized light). Kidney Amyloidosis: Congo Red & Immunofluorescence
    • EM: Non-branching fibrils (7.5-10 nm diameter), randomly arranged.
    • Tubulointerstitial & vascular deposits also occur.
  • Clinical:
    • Nephrotic syndrome (most common).
    • Proteinuria, progressive renal insufficiency.
    • Kidneys: Enlarged or normal-sized.

⭐ Congo Red: Apple-green birefringence (polarized light) is pathognomonic for amyloidosis.

High‑Yield Points - ⚡ Biggest Takeaways

  • Diabetic Nephropathy: Kimmelstiel-Wilson nodules are pathognomonic; leading cause of ESRD.
  • Lupus Nephritis: Class IV (DPGN) is most common and severe; "full-house" immunofluorescence.
  • Hypertensive Nephrosclerosis: Hyaline arteriolosclerosis (benign); hyperplastic "onion-skinning" (malignant).
  • Amyloidosis: Congo Red stain shows apple-green birefringence; commonly causes nephrotic syndrome.
  • Multiple Myeloma: Cast nephropathy (myeloma kidney) is characteristic; Bence Jones proteinuria is key.
  • Goodpasture Syndrome: Anti-GBM antibodies cause linear IgG deposition on IF; nephritis & hemoptysis.
  • ANCA-associated Vasculitis: Typically causes pauci-immune crescentic GN (e.g., GPA, MPA).

Practice Questions: Kidney in Systemic Diseases

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Which type of amyloid is associated with long-term hemodialysis?

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Flashcards: Kidney in Systemic Diseases

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_____ nephropathy is characterized by subepithelial deposits with a 'spike and dome' appearance on electron microscopy

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_____ nephropathy is characterized by subepithelial deposits with a 'spike and dome' appearance on electron microscopy

Membranous

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