Nephritic Syndrome
Acute glomerular inflammation presenting with haematuria (often with red cell casts), proteinuria (usually <3.5g/day), oliguria, hypertension, and oedema. The classical post-streptococcal form occurs 1-3 weeks after pharyngitis or skin infection and is usually self-limiting in children.
Key Facts
Nephritic syndrome is characterised by: haematuria (with red cell casts), proteinuria (<3.5g/day), oliguria, hypertension, and oedema Most common cause in children: post-streptococcal GN (1-3 weeks after group A strep pharyngitis or 3-6 weeks after skin infection) Low C3 with normal C4 is characteristic of post-streptococcal GN (alternative complement pathway); C3 normalises within 8 weeks ASO titre elevated in pharyngitis; anti-DNase B more sensitive for skin infections Post-streptococcal GN in children: self-limiting in >95% with supportive management only Other causes: IgA nephropathy (synpharyngitic), SLE (low C3/C4), ANCA vasculitis, anti-GBM disease, MPGN Red cell casts on urine microscopy are pathognomonic for glomerulonephritis
Overview
Key Facts
Nephritic syndrome reflects acute glomerular inflammation with disruption of the glomerular capillary wall, allowing passage of red blood cells and protein into the urine.
Epidemiology
- Post-streptococcal GN: peak age 5-12 years; rare in adults in developed countries
- IgA nephropathy: most common cause of GN worldwide (but presents as nephritic-nephrotic overlap)
- Incidence of post-infectious GN declining in UK/developed world
Aetiology
Post-infectious (most common in children):
- Group A streptococcus (S. pyogenes) – pharyngitis (1-3 weeks) or impetigo (3-6 weeks)
- Staphylococcal: endocarditis, shunt infections
- Viral: hepatitis B/C
Non-infectious:
- IgA nephropathy
- SLE (class III/IV)
- ANCA-associated vasculitis (GPA, MPA)
- Anti-GBM disease
- MPGN
- Henoch-Schönlein purpura (IgA vasculitis)
Pathophysiology
- Immune complex deposition (subepithelial humps in post-streptococcal) or in situ formation
- Complement activation → neutrophil recruitment → endothelial and mesangial cell proliferation
- Glomerular inflammation → rupture of GBM → haematuria, red cell casts
- Reduced GFR → salt and water retention → hypertension, oedema, oliguria
- Proteinuria results from increased GBM permeability but is usually subnephrotic
Clinical Presentation
Classic Presentation (Post-Streptococcal)
- 1-3 weeks after pharyngitis or 3-6 weeks after skin infection
- Dark/cola-coloured urine (macroscopic haematuria)
- Periorbital oedema (particularly morning)
- Hypertension (can be severe in children)
- Oliguria
- Mild loin/abdominal pain
Other Causes
- IgA nephropathy: haematuria within 1-2 days of URTI (synpharyngitic)
- Lupus nephritis: arthralgia, rash, serositis, multi-system disease
- ANCA vasculitis: constitutional symptoms, pulmonary involvement
Red Flags
- Rapidly rising creatinine → RPGN → urgent biopsy
- Haemoptysis + renal failure → pulmonary-renal syndrome (anti-GBM, ANCA)
- C3 not normalising after 8 weeks → consider MPGN or C3 glomerulopathy
- Adult with nephritic syndrome → higher likelihood of serious pathology; biopsy needed
Differential Diagnosis
| Diagnosis | Key Features | Investigation |
|---|---|---|
| Post-streptococcal GN | 1-3 weeks post-pharyngitis, low C3 | ASO titre, C3 |
| IgA nephropathy | Synpharyngitic (1-2 days), normal complement | Renal biopsy |
| Lupus nephritis | ANA positive, low C3/C4, multi-system | ANA, dsDNA, C3/C4 |
| ANCA vasculitis | Constitutional symptoms, ANCA positive | ANCA, biopsy |
| Anti-GBM disease | Pulmonary haemorrhage, linear IgG | Anti-GBM, biopsy |
| Haemolytic uraemic syndrome | MAHA, thrombocytopenia, renal failure | Blood film, LDH |
Diagnosis / Investigation
Bedside
- Urinalysis: blood +++, protein +/++, red cell casts on microscopy
- Blood pressure: often elevated
- Throat swab: may isolate group A streptococcus
Bloods
- U&Es: creatinine (may be elevated), potassium
- C3/C4: low C3 in post-infectious GN, MPGN, SLE; normal in IgA, ANCA
- ASO titre: elevated 1-3 weeks after streptococcal pharyngitis
- Anti-DNase B: more sensitive for skin infections
- ANA, dsDNA: SLE screen
- ANCA: GPA/MPA screen
- Anti-GBM: Goodpasture screen
- FBC: anaemia (CKD, MAHA), thrombocytopenia (HUS/TTP)
- Blood cultures: if endocarditis-related GN suspected
Imaging
- Renal USS: normal-sized kidneys (acute process)
- Chest X-ray: pulmonary haemorrhage, fluid overload
Special Tests
- Renal biopsy: NOT required for typical post-streptococcal GN in children; indicated in adults, atypical presentation, or failure to improve within 4-6 weeks
Management
Non-pharmacological
- Fluid and sodium restriction during acute phase
- Bed rest: during acute phase
- Monitor fluid balance, daily weights, BP
Pharmacological
Post-streptococcal GN (children):
- Supportive: fluid/salt restriction, antihypertensives (amlodipine, nifedipine)
- Loop diuretics (furosemide): for oedema and hypertension
- Antibiotics: penicillin V for 10 days (eradicate streptococcal carriage; does not alter disease course)
- No immunosuppression required – self-limiting
Other causes:
- Treat underlying disease (SLE → mycophenolate/cyclophosphamide; ANCA → rituximab/cyclophosphamide; anti-GBM → plasma exchange + cyclophosphamide)
Referral Criteria
- All adults with nephritic syndrome → nephrology
- Children with atypical features, failure to improve, or declining renal function
- Suspected RPGN → urgent nephrology
Prognosis
- Post-streptococcal GN in children: >95% make full recovery; complement normalises within 8 weeks
- Adults with post-streptococcal GN: 15-30% develop chronic renal impairment
- IgA nephropathy: 20-40% ESRD at 20 years
- Lupus nephritis: depends on class; class IV has 80-90% renal survival at 10 years with treatment
- ANCA vasculitis: 60-80% renal survival at 5 years
- Anti-GBM: poor if dialysis-dependent at presentation
Other Relevant Information
Complement Levels in Glomerulonephritis
| Disease | C3 | C4 |
|---|---|---|
| Post-streptococcal GN | ↓ | Normal |
| SLE nephritis | ↓ | ↓ |
| MPGN (immune complex) | ↓ | ↓ |
| C3 glomerulopathy | ↓ | Normal |
| IgA nephropathy | Normal | Normal |
| ANCA vasculitis | Normal | Normal |
| Anti-GBM disease | Normal | Normal |
Timing of Haematuria After Infection
| Condition | Interval |
|---|---|
| IgA nephropathy | 1-2 days (synpharyngitic) |
| Post-streptococcal GN | 1-3 weeks (pharyngitis) |
| Post-streptococcal GN | 3-6 weeks (skin infection) |