nephritic syndrome
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"nephritic syndrome" AND glomerulonephritis
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Nephritic Syndrome
Definition
Nephritic syndrome is defined as the clinical constellation of glomerular hematuria (dysmorphic red blood cells or RBC casts in urine), hypertension, edema, reduced GFR (with or without oliguria), and non-nephrotic-range proteinuria. It reflects underlying glomerular inflammation rather than pure permeability defects.
- National Kidney Foundation Primer on Kidney Diseases, 8e, p. 3046
- Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 3054
Pathophysiology
The hallmark is proliferative inflammation within glomeruli, which:
- Severely injures capillary walls - allowing RBCs to escape into urine
- Reduces GFR - causing oliguria, fluid retention (edema), and azotemia
- Activates the renin-angiotensin system - causing hypertension (from both fluid overload and ischemic renin release)
- Causes mild-to-moderate proteinuria (subnephrotic range) because the barrier is disrupted but not purely charge-selective
Key Clinical Features
| Feature | Nephritic | Nephrotic |
|---|---|---|
| Onset | Abrupt | Insidious |
| Hematuria | +++ (RBC casts) | Rare |
| Proteinuria | ++ (< 3.5 g/day) | ++++ (> 3.5 g/day) |
| Edema | ++ | ++++ |
| Blood pressure | Raised | Normal |
| JVP | Raised | Normal/low |
| Serum albumin | Normal/slightly low | Markedly low |
Comprehensive Clinical Nephrology, 7th Edition, Table 16.4
Classic Presentation: Poststreptococcal GN
Children (6-10 years) present 1-4 weeks after pharyngitis or impetigo (group A beta-hemolytic Streptococcus, types 1, 4, 12 - M-protein typed). Features:
- Rapid onset oliguria, weight gain, generalized edema over days
- Brown ("cola-colored") urine - no clots
- Urinalysis: protein, RBCs, RBC casts
- Serum albumin usually normal (proteinuria rarely in nephrotic range)
- Circulating volume expansion - hypertension - risk of pulmonary edema
Comprehensive Clinical Nephrology, 7th Edition, p. 546
Causes Classified by Pathogenesis
1. Immune Complex-Mediated
- Postinfectious/poststreptococcal GN
- Lupus nephritis (proliferative)
- IgA nephropathy / IgA vasculitis (Henoch-Schonlein purpura)
- Cryoglobulinemia
- MPGN type I
- Endocarditis-related GN
2. Pauci-Immune (ANCA-Associated)
- Granulomatosis with polyangiitis (GPA, formerly Wegener's)
- Microscopic polyangiitis
- Eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss)
3. Anti-GBM Antibody-Mediated
- Anti-GBM (Goodpasture) disease - autoantibodies to the alpha-3 chain of collagen IV
- When anti-GBM cross-reacts with pulmonary alveolar BM - pulmonary hemorrhage + renal failure = Goodpasture syndrome
4. Complement Dysregulation
- C3 glomerulopathy (C3 GN, dense deposit disease/MPGN type II)
NKF Primer on Kidney Diseases, 8e, p. 3046; Robbins, Table 20.6
Serum Complement Levels: A Diagnostic Tool
Low Complement (C3/C4 consumed):
- Postinfectious GN (streptococcal, endocarditis, shunt)
- Systemic lupus erythematosus
- Cryoglobulinemia
- C3 glomerulopathies
Normal Complement:
- IgA nephropathy / HSP
- Anti-GBM disease
- ANCA-associated (pauci-immune) RPGN
Goldman-Cecil Medicine, Table 107-4
Rapidly Progressive GN (RPGN) - Crescentic GN
RPGN is the most severe form: kidney function deteriorates over days to weeks. Histologically defined by crescents - proliferative cellular response within Bowman's space.
Three immunologic types:
| Type | Mechanism | Immunofluorescence | Example |
|---|---|---|---|
| Type I (Anti-GBM) | Autoantibodies to GBM | Linear IgG + C3 | Goodpasture syndrome |
| Type II (Immune Complex) | IC deposition | Granular IgG/IgA + C3 | Lupus, post-infectious, IgAN |
| Type III (Pauci-immune) | ANCA-mediated | No deposits | GPA, microscopic polyangiitis |
Treatment of Type I requires plasmapheresis + immunosuppression to remove circulating anti-GBM antibodies. Types II/III require treatment of the underlying disease.
Robbins, Cotran & Kumar, Table 20.6; Comprehensive Clinical Nephrology, p. 558-560
IgA Nephropathy - Most Common Primary Glomerulopathy
- Pathogenesis: deposition of immune complexes containing galactose-deficient IgA1 in the mesangium
- Classic trigger: synpharyngitic (concurrent) macroscopic hematuria during URTIs
- Light microscopy: mesangial proliferation - graded by MEST-C score (Mesangial hypercellularity, Endocapillary proliferation, Segmental sclerosis, Tubular atrophy, Crescents)
- Immunofluorescence: mesangial IgA deposition
- Electron microscopy: mesangial electron-dense deposits
- Prognosis: ~40% progress to kidney failure over 10-20 years; adverse factors include renal insufficiency, hypertension, proteinuria >1 g/24 hr
NKF Primer on Kidney Diseases, 8e, p. 3057-3060
Key Histology Summary (Light / IF / EM)
| Disease | Light Microscopy | Immunofluorescence | Electron Microscopy |
|---|---|---|---|
| Post-infectious GN | Diffuse endocapillary proliferation + neutrophils | Granular IgG + C3 in GBM and mesangium | Subepithelial "humps" (large deposits) |
| Crescentic GN (RPGN) | Crescents + necrosis | Linear (anti-GBM), granular (IC), or none (ANCA) | Varies by type |
| IgA nephropathy | Mesangial proliferation | Mesangial IgA | Mesangial dense deposits |
| MPGN type I | Mesangial/membranoproliferative; GBM splitting ("tram-track") | IgG + C3 + C1q + C4 | Subendothelial deposits |
| Dense deposit disease (MPGN II) | MPGN pattern | C3 only (no Ig, no C1q/C4) | Dense osmiophilic ribbon deposits |
Robbins, Cotran & Kumar, Table 20.5
Management Principles
- General: sodium restriction, loop diuretics for fluid overload, antihypertensives
- ACE inhibitors / ARBs: reduce proteinuria and slow progression in IgAN
- Immunosuppression: steroids +/- cyclophosphamide for ANCA-associated or lupus nephritis
- Plasmapheresis: anti-GBM disease (Goodpasture) to remove circulating antibodies
- Antibiotics: treat underlying infection in post-infectious GN
- Dialysis support: if RPGN leads to acute kidney failure
Memory Aid - Nephritic vs. Nephrotic
- Nephritic = Nephritis = inflammation - think Inflamed, Hematuria, Hypertension, Humps (subepithelial), low GFR
- Nephrotic = Protein pouring out - massive proteinuria (>3.5 g/day), hypoalbuminemia, edema, hyperlipidemia, lipiduria
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