Nephrotic syndrome - Pediatrics Flashcards
Diagnostic triad of nephrotic syndrome
- Proteinuria > 40 mg/h/m2
- Hypalbuminaemia < 2.5 gm/dl
- Oedema
- Hyperlipidaemia (raised LDL and triglycerides) also occurs in most cases, but is not part of the diagnostic triad.
Causes of Nephrotic syndrome
Causes
Most cases of nephrotic syndrome are idiopathic and thought due to T cell disorder that leads to glomerular podocyte dysfunction → increased glomerular permeability.
Types of nephrotic syndrome:
1. There are three main types of nephrotic syndrome in childhood:
A. Minimal change disease (85–90%) → No changes seen under normal microscope but podocyte foot process effacement on electron microscopy
B. Focal segmental glomerular → Focal because not all glomeruli affected (usually deeper ones) sclerosis (10–15%) and segmental because only segments of each glomeruli are affected
C. Membranous nephropathy (1–5%) Associated with hepatitis B and malignancy such as lymphomas (more often seen in adults)
- Congenital nephrotic syndrome (rare)
* Presenting in utero or within the first month of life.
* Several mutations have been found, most notably in the nephrin gene (Finnish congenital nephrotic syndrome). - Secondary nephrotic syndrome to:
* GN with heavy proteinuria
o Systemic lupus erythematosus (SLE)
o Henoch–Schoenlein purpura (HSP)
o Infection: PSGN, HBV, HCV, malaria, Bilharzia
* Drugs as D penicillamine, phenytoin, ….
* Heavy metals (gold).
* Anaphylactoid especially bee sting.
* Tumours: lymphoma/leukaemia.
Clinical picture of Nephrotic syndrome
- Dependent oedema, i.e. Oedema collects at the lowest part, particularly of the face and eyes in the morning.
- As hypoproteinaemia worsens, the oedema becomes widespread and does not improve during the day; sites include the ankles and lower legs, scrotum and sacrum. Ascites can develop and shortness of breath with pleural effusions
- Non-specific symptoms: progressive lethargy and anorexia, occasionally diarrhoea due to GIT oedema.
- Infections, particularly encapsulated organisms such as pneumococcus more likely. Peritonitis also possible (primary or pneumococcal)
- Intravascular hypovolaemia (secondary to hypalbuminaemia) may present with abdominal pain.
- Circulatory collapse/shock or venous thrombosis
Initial investigations in Nephrotic syndrome
1) Urine analysis
* Urine Dipstick for proteinuria → will have +3 or +4 proteinuria
* Albumin: creatinine ratio ≥ 2mg/mg
* 24-hr urine protein: 40 mg/m2/hr
* Sodium concentration < 20 mmol/L is an indication of hypovolaemia
* Microscopy: no or minimal cells in uncomplicated nephrotic syndrome (red and white cell casts in glomerulonephritis)
2)Blood:
* CBC: ↑↑ haematocrit (due to hypovolaemia), evidence of infection, ↑↑ ESR
* Urea and creatinine → raised urea may indicate hypovolaemia
* Serum albumin < 2.5 g/dl (by definition)
* Cholesterol, and triglyceride are ↑↑
3) Other investigations if there is a suggestion of overlap with GN:
* Serum complements → C3 and C4 ↓↓ (except in minimal change)
* ASOT, and anti-DNase B → positive if streptococcal infection
* Throat swab culture for streptococcal infection
* Blood screen for hepatitis B and C and for malaria if travel abroad.
* Renal biopsy if:
o No response to steroids after 4–6 weeks (SRNS) or frequent relapses.
o Atypical presentation, e.g. hypertension, gross haematuria, high creatinine, infant < 1 year or > 12 y
Differential diagnosis of Nephrotic syndrome
1) Generalized oedema → cardiac, hepatic, nutritional, allergic
2) Other causes of proteinuria
* Orthostatic proteinuria
* Increased glomerular filtration pressure
* Reduced renal mass
* Tubular proteinuria.
complications of nephrotic syndrome
- Intra vascular thrombosis: due to hypovolemia (sluggish circulation), ↑↑ Platelet adhesiveness, and ↓↓ anti-thrombin III, protein S & protein C. in the form of: cerebral cortical veins. renal vein thrombosis. deep venous thrombosis.
- Infections: due to –
o Loss of immunoglobulins.
o Loss of complement factor (properdin factor B).
o Oedema fluid favour infection
o Immuno-suppressive treatment
Common organisms: Commonly capsulated bacteria → Pneumococci, E. coli, H. influenza, Staph aureus. - Acute renal failure: due to: - severe hypovolemia, ↓↓ renal blood flow (prerenal failure), and renal vein thrombosis.
- Relapse:
Definition: Recurrence of significant proteinuria (≥ 3+) found on 3 consecutive days having been in remission previously.
If > 4 relapses within 1 year→ frequent relapsing NS. - Complications of drugs
o Corticosteroids as hypertension, cataract, infections, growth retardation, diabetes mellitus, osteoporosis, adipose tissue hypertrophy (moon face, buffalo hump, truncal obesity).
o Cyclophosphamide: alopecia, bone marrow suppression, and cystitis (haemorrhagic).
o Cyclosporin A: hirsutism, nephrotoxic and hepatotoxic.
Treatment of nephrotic syndrome
❖ Supportive:
* Hospitalization: for follow up of 24 hr urine protein, urinary output, weight gain, and blood pressure.
* Diet control in the form of salt restriction, and increased protein intake. Fluid restriction in case of progressive weight gain.
* Control of infection → either latent UTI, giving pneumococcal and H. influenzae vaccine for chronic cases
* Salt free albumin and diuretics by giving salt free albumin (0.5-1 gm/kg over 4 hrs) followed by frusemide (1-2 mg/ kg)
❖ Curative:
* Induction of remission by Prednisone 2mg/kg/day for 4 weeks in 3 divided doses
* Response either:
- Remission → Steroid sensitive NS → (proteinuria < 4 mg/m2/hr and serum albumin ≥ 3.5 gm/dl) followed by gradual withdrawal over 6 weeks and follow up
- Relapse (10%) that need to restart treatment. Steroid dependent or frequent relapses need to restart treatment until remission followed by alternate day steroid therapy for 12-18 months ± cyclophosphamide 2mg/kg/day or cyclosporin A for 1 year. Rituximab (anti CD 20 monoclonal antibody) can be used in steroid dependent cases.
- Steroid resistance NS → can be given:
1. Calcineurin inhibitors like Cyclosporin A or Tacrolimus.
2. Anti-proteinuria agents like ACE inhibitors and angiotensin II blockers
