Secondary glomerular diseases

Diabetic Nephropathy - Sweet Kidney Trouble

• Patho: Non-enzymatic glycation → hyaline arteriolosclerosis (efferent > afferent) → initial hyperfiltration (↑ GFR). Progresses to glomerular basement membrane (GBM) thickening & mesangial expansion.
• Hallmark: Kimmelstiel-Wilson (KW) nodules (PAS-positive, nodular glomerulosclerosis).
• Clinical: Earliest sign is microalbuminuria (Urine Albumin-to-Creatinine Ratio 30-300 mg/g). Often co-exists with retinopathy.
• Management: Strict glucose (HbA1c <7%) & BP control (<130/80 mmHg).
  • First-line: ACE inhibitors or ARBs.
  • Add-on: SGLT2 inhibitors (e.g., -gliflozins) for renoprotection.

⭐ ACE inhibitors are first-line to slow nephropathy progression, even in normotensive patients with microalbuminuria, by reducing intraglomerular pressure.

Lupus Nephritis - Wolf in the Filters

• Pathogenesis: Type III hypersensitivity. DNA/anti-dsDNA immune complex deposition in glomeruli.
• Presentation: Varies from asymptomatic hematuria/proteinuria to overt nephritic or nephrotic syndrome.
• Diagnosis: Renal biopsy is the gold standard for staging. Key serologies: ↑ ANA, ↑ anti-dsDNA, ↓ C3/C4.

• ISN/RPS Classification & Treatment:
  • Class III/IV (Focal/Diffuse Proliferative): Most common & severe. Aggressive therapy with steroids + Mycophenolate Mofetil (MMF) or Cyclophosphamide.
  • Class V (Membranous): Presents with nephrotic syndrome. Treat with steroids + MMF.

⭐ Full House Immunofluorescence: On biopsy, staining is positive for IgG, IgA, IgM, C3, and C1q-a classic finding for lupus nephritis.

Amyloid & Paraproteins - Misfolded Mess

• Pathophysiology: Extracellular deposition of insoluble, misfolded fibrillar proteins (β-pleated sheets).
• Amyloidosis:
  • AL (Primary): Monoclonal light chain deposition from plasma cell dyscrasias.
  • AA (Secondary): Serum Amyloid A deposition from chronic inflammation (e.g., RA, IBD).
  • Diagnosis: Congo Red stain shows classic apple-green birefringence under polarized light.
  • Presentation: Nephrotic syndrome, enlarged kidneys.
• Light Chain Cast Nephropathy (Myeloma Kidney):
  • Filtered monoclonal light chains (Bence-Jones proteins) are directly toxic to tubules, forming obstructing casts.

⭐ Bence-Jones proteins in urine are not detected by standard urine dipstick, which primarily detects albumin. Suspect this in patients with high total protein but negative/trace dipstick protein.

Vasculitis & Infections - Inflammatory Attack

• ANCA-Associated Vasculitis (Pauci-Immune GN): Rapidly progressive GN.
  • Granulomatosis with Polyangiitis (GPA): c-ANCA (anti-PR3). Affects sinuses, lungs, kidneys. 📌 C-disease: C-ANCA.
  • Microscopic Polyangiitis (MPA): p-ANCA (anti-MPO). Affects lungs, kidneys; no granulomas.
  • EGPA (Churg-Strauss): p-ANCA, eosinophilia, asthma.
• Immune Complex GN:
  • IgA Vasculitis (HSP): Follows URI. Palpable purpura, arthralgia, abdominal pain.
  • Infection-Related GN: Post-strep (PSGN), endocarditis. Features ↓ C3.

⭐ GPA classically presents with a triad: 1) upper respiratory tract disease (sinusitis), 2) lower respiratory tract disease (hemoptysis), and 3) glomerulonephritis.

• Diabetic nephropathy is the leading cause of ESRD; Kimmelstiel-Wilson nodules are pathognomonic.
• Lupus nephritis is characterized by immune complex deposition and a “full-house” immunofluorescence pattern.
• Amyloidosis shows apple-green birefringence with a Congo red stain under polarized light.
• Goodpasture syndrome features anti-GBM antibodies against type IV collagen, creating a linear IF pattern.
• GPA (Wegener’s) is a pauci-immune GN strongly associated with c-ANCA (anti-PR3).
• IgA vasculitis (HSP) typically presents with palpable purpura, arthralgias, and renal involvement.