What is the difference between nephrotic and nephritic syndrome?
The glomerulus can fail in two broad ways. If the filtration barrier becomes leaky (mainly podocyte and basement membrane injury without much inflammation), protein pours into the urine — nephrotic syndrome. If the glomerulus is inflamed (immune complexes, antibodies, neutrophils), capillary walls break and red cells leak out while filtration falls — nephritic syndrome.
| Feature | Nephrotic | Nephritic |
|---|---|---|
| Core defect | Increased glomerular permeability (podocyte/GBM) | Glomerular inflammation |
| Proteinuria | ≥ 3 g/24 h (or spot ≥ 2 g/g creatinine); children ≥ 40 mg/m²/h | Variable, usually sub-nephrotic |
| Urine sediment | Bland; lipid droplets (lipiduria) | RBC casts, dysmorphic RBCs (acanthocytes), cola-coloured urine |
| Blood pressure | Usually normal early | Raised |
| Urine output / GFR | Often preserved | Oliguria, rising creatinine |
| Oedema | Marked — periorbital in children, dependent in adults | Mild to moderate |
| Other | Hypoalbuminaemia, hyperlipidaemia, thrombosis, infections | Azotaemia; may progress to RPGN |
Why does nephrotic syndrome cause oedema, hyperlipidaemia and thrombosis?
Albumin makes up about 85% of the protein lost. Heavy proteinuria lowers serum albumin, oncotic pressure falls and fluid shifts into tissues — oedema starts in the face of children and in dependent areas in adults. Low oncotic pressure also drives hepatic lipoprotein synthesis, raising cholesterol and triglycerides (hyperlipidaemia); lipid droplets appear in the urine. A dipstick reading of 3+ (about 300 mg/dL) corresponds to a loss of 3 g or more a day.
- Thrombosis: urinary loss of antithrombin III in heavy proteinuria makes patients hypercoagulable — deep vein thrombosis, pulmonary embolism or renal vein thrombosis (flank pain with haematuria) can be the first sign. See Virchow's triad.
- Infections: loss of immunoglobulins predisposes children to sepsis, pneumonia and peritonitis.
- Causes by group: in White adults the commonest primary cause is membranous nephropathy; in people of African ancestry it is FSGS. Diabetic nephropathy is the most common cause of nephrotic syndrome overall. In children over 1 year, minimal change disease dominates.
What are the light, IF and EM findings in MCD, FSGS and membranous nephropathy?
| Disease | Light microscopy | Immunofluorescence | Electron microscopy | Key associations |
|---|---|---|---|---|
| Minimal change disease | Normal (minimal) change | Negative | Diffuse effacement of podocyte foot processes | 70–90% of childhood nephrotic syndrome (age > 1 year); 10–15% in adults; excellent steroid response |
| FSGS | Segmental sclerosis/hyalinosis in some glomeruli; 5 variants | IgM and C3 in sclerotic segments | Foot process effacement | Commonest in African ancestry; APOL1 variants; HIV → collapsing variant |
| Membranous nephropathy | Diffuse GBM thickening; spikes on silver stain | Granular IgG4 along capillary walls (IgG1/IgG3, C1q 'full house' in lupus) | Subepithelial deposits; 'spike and dome' | Anti-PLA2R in 70–80% of primary MN; renal vein thrombosis |
Minimal change disease (MCD) — also called nil disease or lipoid nephrosis — shows almost nothing on light microscopy; electron microscopy reveals effacement of podocyte foot processes. Children frequently achieve remission with steroids within 4 weeks. A typical regimen is prednisolone 1 mg/kg for 4 to 16 weeks; relapses are common, and when cyclophosphamide is added it is started only after steroid-induced remission.
Focal segmental glomerulosclerosis (FSGS) is classified histologically into five variants — perihilar, tip, cellular, collapsing and not otherwise specified (NOS). Accumulation of acellular matrix and hyaline deposits obliterates capillaries in a segmental pattern. Collapsing FSGS (HIV-associated nephropathy) progresses rapidly to end-stage disease, and about 50% of patients with persistent nephrotic-range proteinuria reach end-stage kidney disease within 3 to 8 years.
Membranous nephropathy (MN) is primary in 75–80% — driven by autoantibodies, most often against the phospholipase A2 receptor (PLA2R, 70–80%), with smaller groups against THSD7A (1–5%) and NELL1. Secondary MN (20–25%) follows infections such as hepatitis B, hepatitis C, syphilis, malaria, HIV and schistosomiasis, lupus and other causes; the work-up for secondary causes includes age-appropriate cancer screening. The serum anti-PLA2R antibody test is increasingly replacing biopsy and tracks disease activity. About one-third remit spontaneously with conservative care.
How does post-streptococcal glomerulonephritis present?
Post-streptococcal (post-infectious) GN is the classic nephritic syndrome of children: cola-coloured urine, periorbital puffiness, hypertension and oliguria after a latent period — typically 1 to 2 weeks after pharyngitis and 2 to 4 weeks after a skin infection such as pyoderma. The latent period distinguishes it from IgA nephropathy, where haematuria coincides with the infection.
| Test | Finding |
|---|---|
| Serum C3 | Low in the acute phase (alternative pathway activation); returns to normal within 6 to 8 weeks |
| ASO titre | Raised after pharyngitis; rises in 1–3 weeks, peaks at 3–5 weeks, normal by 6 months |
| Light microscopy | Enlarged, hypercellular glomeruli — endocapillary proliferation with many neutrophils |
| Immunofluorescence | Granular IgG/C3 — starry sky, garland or mesangial patterns |
| Electron microscopy | Large subepithelial 'humps' |
Prognosis in children is excellent, with complete recovery usually within 6 to 8 weeks. In adults the picture has shifted: staphylococcal infection-associated GN (skin infections, endocarditis, osteomyelitis, pneumonia; intravenous drug use is a major risk factor) is now the commonest infection-related GN in Western countries, and the glomerulonephritis may occur during the infection rather than after it.
What are the key features of IgA nephropathy?
IgA nephropathy (Berger disease) is the most common glomerulonephritis worldwide. Its typical story is synpharyngitic macroscopic haematuria — brown or 'coca-cola' urine at the same time as an upper respiratory infection — often recurring with later infections.
- Pathogenesis: galactose-deficient IgA1 forms immune complexes that deposit in the mesangium.
- Biopsy: mesangial proliferation with dominant mesangial IgA on immunofluorescence and mesangial electron-dense deposits.
- Prognosis: the Oxford MEST-C score (mesangial and endocapillary hypercellularity, segmental sclerosis, tubular atrophy/interstitial fibrosis, crescents) predicts outcome.
- Serum IgA lacks sensitivity and specificity — diagnosis needs a biopsy.
- Fewer than 5% present with acute kidney injury (crescents or tubular damage from heavy haematuria).
- IgA vasculitis (Henoch-Schönlein purpura) is the systemic counterpart with the same kidney lesion.
What are the types of rapidly progressive glomerulonephritis?
Rapidly progressive GN (RPGN) means loss of kidney function over days to weeks, a nephritic urine and crescents in Bowman space (proliferating parietal epithelial cells). It is often called crescentic GN; the term is usually applied when more than half of glomeruli have crescents, though even one crescent signals active disease.
| Type | IF pattern | Causes | Notes |
|---|---|---|---|
| I — anti-GBM | Linear IgG along GBM | Anti-GBM disease; with lung haemorrhage = Goodpasture syndrome | Antibody against the non-collagenous domain of the α3 chain of type IV collagen; 10–15% of crescentic GN; alveolar haemorrhage in 40–60% |
| II — immune complex | Granular | Post-infectious GN, lupus nephritis, IgA nephropathy, IgA vasculitis, cryoglobulinaemia | 25–30% of RPGN; commoner in children and in lower-income countries |
| III — pauci-immune | Little or no deposits | ANCA-associated vasculitis (PR3 or MPO) | Commoner in adults; about 25% progress to end-stage kidney disease |
| IV — double positive | Linear + ANCA | Both ANCA and anti-GBM antibodies | ANCA often precedes anti-GBM |
Treatment is urgent: corticosteroids with immunosuppression for anti-GBM, ANCA-associated and lupus RPGN, with plasma exchange for anti-GBM disease. Anti-GBM antibody levels are checked every 1 to 2 weeks until two consecutive results a week apart are negative. Immune-complex RPGN generally has a better outcome than anti-GBM or pauci-immune disease, except lupus class IV.
What are the common exam traps in glomerular disease?
- Normal light microscopy + nephrotic child → MCD; EM shows foot process effacement (also seen in FSGS, so EM alone does not separate them).
- 'Spike and dome' / subepithelial deposits / anti-PLA2R → membranous nephropathy, not PSGN (PSGN has humps).
- Starry sky or garland IF + low C3 + latent period → post-streptococcal GN.
- Linear IgG → anti-GBM (type I RPGN). Granular → immune complex (type II). Pauci-immune → ANCA (type III).
- Collapsing FSGS → HIV-associated nephropathy; APOL1 variants increase risk.
- 'Full house' IF (IgG, IgA, IgM, C3, C1q) → lupus.
- Most common GN worldwide → IgA nephropathy; most common nephrotic cause overall → diabetic nephropathy.