Nephritic syndrome

	PSGN	IgA Nephropathy	Alport Syndrome	RPGN (Crescentic)	DPGN (Lupus)	MPGN
Classic Patient	Child, 2-4 wks post-GAS infx	Young adult, syn-pharyngitic	Boy w/ fam hx of renal failure & deafness	Pt w/ acute, rapid GFR decline	Patient with SLE	Assoc. w/ HCV, cancer, or autoimmune dz
Pathophysiology	Type III HSR; IC deposition	Mesangial IgA IC deposition	X-linked defect in Type IV Collagen	GBM breaks → fibrin influx	Type III HSR; diffuse IC deposition	IC deposition or complement dysregulation
Key Features / Labs	↓↓ C3, ↑ASO titer	Normal C3, episodic gross hematuria	Hematuria, sensorineural deafness, ocular defects	Anti-GBM Ab, p/c-ANCA depending on type	↓↓ C3/C4, +anti-dsDNA	↓↓ C3 (persistent), +HCV serology
LM/IF/EM	Subepithelial humps (EM), hypercellular “lumpy bumpy” (LM), granular IgG/C3 (IF)	Mesangial IgA deposits (IF)	“Basket-weave” GBM (EM)	Crescents (LM); IF defines type (linear, pauci, granular)	“Wire loops” (LM), subendothelial deposits (EM), “full-house” (IF)	“Tram-track” GBM (LM)
Key Fact	Prognosis excellent in children	Most common GN worldwide.	”Can’t see, can’t pee, can’t hear a high C”	A histologic pattern, not a single disease.	Most common & severe nephritis in SLE.	Strong association with Hepatitis C (Type I).

Etiology

Tip

• The most common cause of nephritic syndrome is immune complex deposition, which leads to serum hypocomplementemia.
• IgA nephropathy is an exception, which is characterized by normal serum complement levels

• ANCA-associated glomerulonephritis (pauci-immune glomerulonephritis)
  • Granulomatosis with polyangiitis
  • Microscopic polyangiitis
  • Eosinophilic granulomatosis with polyangiitis
• Anti-glomerular basement membrane (GBM) associated glomerulonephritis
  • Anti-GBM disease (Goodpasture disease)
  • Anti-GBM glomerulonephritis (no lung involvement)
• Immune complex-mediated glomerulonephritis
  • Low C3 levels
    • Lupus nephritis
    • Infection-related glomerulonephritis
      • Poststreptococcal glomerulonephritis
  • Normal C3 levels
    • IgA nephropathy
    • IgA vasculitis

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Classifications

• Poststreptococcal glomerulonephritis
• Diffuse proliferative glomerulonephritis
• Rapidly progressive glomerulonephritis

Pathophysiology

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Clinical features

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Diagnostics

• Initial: Urinalysis (UA) showing microscopic/macroscopic hematuria, dysmorphic RBCs, RBC casts, and sub-nephrotic range proteinuria (< 3.5 g/day).
• Key Labs:
  • Renal function: Elevated BUN and serum Cr.
  • Serum complements:
    • Decreased C3/C4: PSGN, Lupus Nephritis, Membranoproliferative GN (MPGN).
    • Normal C3/C4: IgA Nephropathy, Granulomatosis with Polyangiitis (GPA), Microscopic Polyangiitis (MPA), Goodpasture syndrome.
  • Serology: Anti-streptolysin O (ASO) or anti-DNase B (PSGN); ANA and anti-dsDNA (SLE); c-ANCA/PR3 (GPA); p-ANCA/MPO (MPA); anti-GBM antibodies (Goodpasture).
• Confirmatory/Gold Standard: Renal biopsy (not always needed in classic pediatric PSGN, but required in adults or progressive cases).
  • PSGN: LM shows diffuse hypercellularity; IF shows granular deposition (“lumpy-bumpy” C3/IgG); EM shows subepithelial humps.
  • IgA Nephropathy: IF shows IgA-dominant immune complex deposition in the mesangium.
  • Goodpasture Syndrome: IF shows linear IgG deposition along the GBM.
  • RPGN: LM shows crescents composed of fibrin and macrophages.
  • Pauci-immune GN (GPA/MPA): Biopsy shows necrotizing GN with minimal or absent immune complexes on IF.

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Treatment

• First-line / Acute Stabilization:
  • Fluid and Sodium Restriction: Control volume overload.
  • Loop Diuretics (e.g., Furosemide): First-line for edema and volume-dependent HTN. c
  • Antihypertensive Therapy: Calcium channel blockers or vasodilators if HTN persists acutely.
  • Caution: Hold ACEi/ARBs during acute oliguric AKI / severe hyperkalemia; introduce later for persistent proteinuria.
• Etiology-Specific Interventions:
  • PSGN: Supportive therapy; antibiotic treatment only if active GAS infection remains (Abx do not alter the course of GN).
  • IgA Nephropathy: ACEi/ARBs if persistent proteinuria (>1 g/day) and stable GFR; systemic steroids for progressive disease.
  • Rapidly Progressive GN (RPGN) / ANCA / Lupus class III/IV: High-dose IV pulse Methylprednisolone + Cyclophosphamide or Rituximab.
  • Anti-GBM (Goodpasture): Urgent Plasmapheresis (to remove circulating antibodies) + corticosteroids + cyclophosphamide.
• Refractory / Emergent:
  • Urgent Hemodialysis: Indicated for refractory AEIOU:
    • Acidosis (pH < 7.1 refractory to medical Rx).
    • Electrolytes (severe refractory hyperkalemia > 6.5 mEq/L with ECG changes).
    • Ingestion/Toxins.
    • Overload (pulmonary edema unresponsive to high-dose loop diuretics).
    • Uremia (uremic pericarditis, encephalopathy, uremic bleeding).

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