Clinical reasoning notes. The two syndromes are the classic exam confusion: learn the pattern, then the causes.
The reasoning chain: look at the urine and the blood pressure → name the syndrome (nephrotic or nephritic) → find the cause (primary or secondary, with local causes) → confirm with serology and, if needed, biopsy → treat the cause, control oedema, protect the kidney, prevent complications.
1. The core difference
| Nephrotic syndrome | Nephritic syndrome | |
|---|---|---|
| Main problem | Heavy protein loss through a leaky filter | Inflammation of the glomerulus |
| Urine | Protein above 3.5 g/day (a protein:creatinine ratio above 300 mg/mmol); frothy | Blood (red cell casts, dysmorphic red cells), modest protein |
| Blood | Low albumin (below 25–30 g/L), high cholesterol | Raised urea and creatinine |
| Oedema | Gross (face, legs, ascites, effusions) | Mild |
| Blood pressure | Normal or low | High |
| Urine volume | Normal | Reduced (oliguria) |
| Typical | Child: minimal change disease | Child after throat infection: PSGN |
Mnemonic: nephrotic = protein (tonnes of it); nephritic = blood and pressure.
2. Causes of nephrotic syndrome
- Children: minimal change disease (about 90% under 10 years; responds to steroids; normal light microscopy).
- Adults: focal segmental glomerulosclerosis (FSGS), membranous nephropathy, minimal change.
- Secondary causes: diabetes mellitus (the commonest worldwide), HIV-associated nephropathy, hepatitis B and C, malaria (quartan), schistosomiasis, SLE, amyloidosis, drugs (NSAIDs, gold, penicillamine), cancers (membranous nephropathy with solid tumours; minimal change with Hodgkin lymphoma).
3. Causes of nephritic syndrome
| Cause | Clues |
|---|---|
| Post-streptococcal GN (PSGN) | 1–3 weeks after a throat or skin infection; low C3, raised ASO; usually self-limiting in children |
| IgA nephropathy | Haematuria during or just after an upper respiratory infection; normal complement |
| Rapidly progressive GN (RPGN) | Creatinine rises over days to weeks; crescents on biopsy; causes: anti-GBM (Goodpasture), ANCA vasculitis, immune complex disease |
| Lupus nephritis | Young woman, arthralgia, rash; low C3 and C4, anti-dsDNA |
| Infective endocarditis, hepatitis B/C, HIV, shunt nephritis | Think of the infection that drives it |
4. Investigate with purpose
| Test | The question it answers |
|---|---|
| Urinalysis and microscopy | Protein (nephrotic) or red cell casts (nephritic)? |
| Urine protein:creatinine ratio, 24-hour protein | How heavy is the proteinuria? |
| Albumin, cholesterol, creatinine, electrolytes | Severity of nephrotic syndrome; kidney function |
| Complement C3 and C4 | Low in PSGN, lupus, and some membranoproliferative disease |
| ASO titre, anti-DNase B, throat or skin swab | Streptococcal link |
| ANA, anti-dsDNA, ANCA, anti-GBM | Autoimmune cause |
| HIV, hepatitis B and C, malaria tests, blood glucose | Secondary causes |
| Kidney ultrasound | Size; obstruction; chronic disease |
| Renal biopsy | Adults with nephrotic syndrome, any RPGN, steroid-resistant disease, children older than 10 |
Where results can mislead: a normal creatinine does not exclude significant disease; ASO may be normal in skin-related PSGN (use anti-DNase B); in a child, do not biopsy first: treat with steroids and biopsy if there is no response.
5. Management
Nephrotic syndrome
- Oedema: salt restriction and a loop diuretic. Albumin infusion only for severe, resistant oedema.
- Reduce proteinuria and protect the kidney: an ACE inhibitor or ARB.
- Treat the cause: corticosteroids for minimal change disease (children respond in most cases), other immunosuppression for FSGS and membranous nephropathy; treat HIV, hepatitis and diabetes.
- Prevent complications: infection (pneumococcal vaccine, prompt antibiotics for peritonitis), venous thrombosis (loss of antithrombin in the urine: consider anticoagulation in high-risk patients), hyperlipidaemia (statin), acute kidney injury.
Nephritic syndrome
- Treat hypertension and fluid overload (salt and fluid restriction, diuretics, calcium channel blockers).
- PSGN: supportive care and a course of penicillin for the infection; most children recover.
- RPGN and lupus nephritis: an emergency: high-dose steroids, cyclophosphamide, plasma exchange for anti-GBM, and renal support. Delay costs kidney function.
- Monitor creatinine, urine output and weight; refer early for dialysis if red flags appear (see the note on acute kidney injury).
Examiner questions
- Contrast nephrotic and nephritic syndromes in a table.
- A 5-year-old has gross oedema and heavy proteinuria. What is the most likely diagnosis, and what is the first treatment?
- Why are nephrotic patients prone to thrombosis and infection?
Practice questions
1. A 6-year-old has facial puffiness, 4+ protein, albumin 18 g/L and normal blood pressure. The first treatment is: A. Renal biopsy · B. Corticosteroids · C. Plasma exchange · D. Antibiotics only · E. Dialysis Answer: B. Minimal change disease is the most likely cause.
2. A child with haematuria, hypertension and low C3 two weeks after a skin infection most likely has: A. IgA nephropathy · B. Minimal change disease · C. Post-streptococcal glomerulonephritis · D. Anti-GBM disease · E. FSGS Answer: C.
3. Which feature points to nephrotic rather than nephritic syndrome? A. Hypertension · B. Red cell casts · C. Oliguria · D. Heavy proteinuria with hypoalbuminaemia and hypercholesterolaemia · E. Low C3 Answer: D.
4. Crescents on renal biopsy are the hallmark of: A. Minimal change disease · B. Membranous nephropathy · C. Rapidly progressive glomerulonephritis · D. Diabetic nephropathy · E. Amyloidosis Answer: C.