Nephrotic syndrome

Criteria

1. Edema
2. Proteinuria (at least 3+)
3. Hypoalbuminemia usually plus Hyperlipidemia

Causes

Primary:

Minimal change disease, Focal segmental glomerulosclerosis, Membranoproliferative glomerulonephritis

Secondary:

Hepatitis B, HIV, Lupus, Postinfectious GN, Subacute infective endocarditis

Congenital:

Occur in children less than 1 year of age

Important points in history

• Signs of systemic disease like joint complaints, rash, fever
• Preceding symptoms or illnesses (e.g. respiratory, skin or urinary tract infections)
• Edema
• Urine output (frequency and volume – oliguria/anuria), and colour, foamy urine , hematuria
• Abdominal pain, flank pain
• Breathlessness, cough
• Headache, fits (hypertension)
• Past medical history of similar problem
• Family history of renal problems, high blood pressure etc.

Important points on examination

• Vital signs, blood pressure
• Accurate baseline weight
• Site and extent of oedema, puffy eyelids, scrotal swelling
• Respiratory exam (pulmonary oedema, shortness of breath?)
• Abdominal examination (enlarged kidneys, ascites)
• Fever and signs of specific infections, e.g. previous skin infections

Differential diagnosis

Congestive heart failure, Kwashiokor , liver cirrhosis, protein-losing enteropathy

Investigations

1. Urine dipstick (proteinuria) and microscopy
2. FBC, Crea, Albumin
3. K and Na, if available
4. HIV test
5. Hepatitis B and C
6. VDRL, malaria parasites
7. Treat for Schistosomiasis
8. Kidney ultrasound

Consider LFTs if cirrhosis possible underlying cause

Complications

1. Infections
2. Thromboembolism (Doppler Ultrasound)
3. Acute kidney injury
4. Hypovolemia
5. Protein malnutrition
6. Hyperlipidemia

Management - first episode

1. Admit
2. Salt restriction, fluid restriction if fluid overload
3. Stat dose Praziquantel
4. Monitor daily: blood pressure, weight (target daily weight loss) and urine dipstick until normal
5. Encourage mobilization (bed rest may increase risk of venous thrombosis.)
6. Consider prophylactic Amoxicillin if hypoalbuminemia
7. Steroids
   • Prednisolon 2mg/kg/d 4-6 weeks
   • If no response in 4 weeks, continue 2mg/kg or 2-4 weeks longer (not more than 8 weeks)
   • If no response in 8 weeks, the child has steroid resistant nephrotic syndrome => wean off steroids fast
   • If response, continue 1.5mg/kg alternate days for 4 weeks and then wean off during 4 weeks
   • Total duration of steroids should be 2-3 months after remission is achieved
8. Diuretics, if severely fluid overloaded
   • Furosemide 1mg/kg iv (maximum 40mg) 2-3 times daily
   • If no response after few days, combine
     • First choice HCT 1-2mg/kg OD (max 50mg/day)
     • Spironolactone 1-3mg/kg in 2 divided doses (max 100mg/day) if creatinine is normal
9. Pneumococcal vaccine, if available, and not previously immunized

Management - relapses

The same as above, except

• Can often be treated as outpatients (if close follow up possible, always admit if respiratory distress, signs of renal failure, hypertension, severe infection)
• Prednisolone 2mg/kg per day day until the urine protein tests are negative or trace for three consecutive days, followed by 1.5mg/kg alternate days for four weeks. Then taper over two months (total length of treatment 3 months)
• In frequent relapses taper slower and considering keeping the patient on small dose alternate day Prednisolon for 12-18 months, if no severe side effects.
• If severe side effects of steroids or the patient needs high dose prednisolone to maintain remission, consider cyclophosphamide (2mg/kg in
2 divided doses for 8-12 weeks (max cumulative dose of 168 mg/kg))
• In frequent relapses or steroid resistant NS
  • ACE-inhibitors: Enalapril 0.2-0.5mg/kg/day (max 20mg/day)
  • Diuretics, as above
  • Symptomatic treatment - therapeutic ascetic taps, pleural taps
  Calciumcarbonate 500mg OD and vitamin D 2000-4000IU OD (Usually only in Private Pharmacies))
• Steroid resistant NS is likely to be also cyclophosphamide resistant, especially in younger children
• Optimally the patient would need kidney biopsy

Follow up

In renal clinic

Prognosis

In minimal change disease the prognosis is good. Other causes of glomerulonephritis may progress to end stage kidney disease, especially if no response on treatment.

Definitions

1. Steroid resistant NS: after 8 weeks of daily steroids at 2mg/kg the patient is still nephrotic
2. Frequently relapsing NS: able to wean steroids and/or stop steroids, but the patient relapses either twice in 6 months or four times in a year
3. Steroid dependant NS: Patient responds to steroids and remits, but unable to stop steroids