Nephrotic Syndrome

bubbles appearing on the surface of the urine indicate renal disease and a prolonged illness discloses chronic inflammatory activity in the glomeruli and may be identified with the term chronic glomerulonephritis' Hippocrates, Aphorisms VII, 34(6)(1)

Introduction
Nephrotic syndrome is defined as a combination of albuminuria with hypoalbuminemia, leading to edema, accompanied by hyperlipidemia and lipiduria.

Nephrotic Syndrome
Oedema Proteinuria > 40mg/m2/hour (1g/m2/day) or an early morning urine protein creatinine index of 200mg/mmol (>3.5mg/mg) Hypoalbuminaemia (<25g/l) Hypercholesterolaemia

Nephrotic Syndrome

Primary
1. Idiopathic 1. 2. 3. 4. 5. 6. 7.

Secondary
Post streptococcal glomerulonephritis Lupus erythematosus Diabetes mellitus Amyloidosis Viral infections (e.g. hepatitis B, hepatitis C, HIV) Drugs (e.g. peniclllamine, gold, mercury, NSAIDs) Toxins and allergens (e.g. bee sting and food allergy)

Pathology Types
Minimal change glomerulonephritis Focal segmental glomerulosclerosis Membranous glomerulonephritis Proliferative glomerulonephritis (mesangial, IgA nephropathy).

Minimal Change Glomerulonephritis

the most common histologic form of nephrotic syndrome, seen in 70% to 80% of cases. Males are affected more frequently than females by a 2 : 1 ratio. Most children younger than 7 years old with nephrotic syndrome have MCNS. Children 7 to 16 years old with nephrotic syndrome have a 50% chance of having MCNS. A trial of steroid therapy is indicated before biopsy in these older children if the presentation is typical.

Focal Segmental Glomerulosclerosis

The initial presentation of focal segmental glomerulosclerosis (FSGS) is usually identical to that of MCNS. FSGS may progress from MCNS or present as a separate entity. A circulating factor that increases glomerular permeability to albumin is found in some patients with FSGS. FSGS accounts for approximately 10% of children with nephrotic syndrome.

Membranous nephropathy
Membranous nephropathy is infrequent in childhood. Approximately 1% of children with nephrotic syndrome have this lesion on a kidney biopsy specimen. It is seen most commonly in adolescents and children with systemic infections, such as hepatitis B, syphilis, malaria, and toxoplasmosis, or receiving drug therapy (gold salts, penicillamine). Hematuria is common.

Congenital nephrotic syndrome

Congenital nephrotic syndrome is defined as clinical nephrotic syndrome that presents during the first 6 months of life. There are two common types. The Finnish type is an autosomal recessive disorder most common in persons of Scandinavian descent and is due to a mutation in a component protein in the glomerulus filtration slit. The second type is a heterogeneous group of abnormalities including diffuse mesangial sclerosis and conditions associated with drugs or infections. Prenatal diagnosis is suspected if there are elevated levels of maternal alpha-fetoprotein. Secondary forms of nephrotic syndrome may be due to systemic lupus erythematosus and infections (syphilis, hepatitis B)

Mechanism of Oedema
Proteinuria
Hypoproteinemia

Decreased Plasma oncotic pressure

Oedema Formation Decreased intravascular volume Renal Salt and Water Retention

Clinical Features
Periorbital oedema particularly on waking Scrotal or vulva oedema Leg and ankle oedema Ascites Breathlessness due to pleural effusions and abdominal distension

Investigation
Full blood count Renal profile Serum cholesterol Liver function tests
Particularly serum albumin

Urinalysis, urine culture Quantitative urinary protein excretion

creatinine ratio or 24 hour urine protein

Further Investigation
Antinuclear factor / anti-dsDNA to exclude SLE. Serum complement (C3, C4) levels to exclude SLE, post-infectious glomerulonephritis. ASOT titres to exclude Post-streptococcal glomerulonephritis.

Management
A normal protein diet with adequate calories is recommended. No added salt to the diet when child has oedema. Penicillin V 125 mg BD (1-5 years age), 250 mg BD (6-12 years), 500 mg BD (> 12 years) is recommended at diagnosis and during relapses, particularly in the presence of gross oedema.

Management
Check for signs and symptoms which may indicate
Hypovolaemia: Abdominal pain, cold peripheries, poor capillary refill, poor pulse volume with or without low blood pressure; OR Hypervolaemia: Basal lung crepitations, rhonchi, hepatomegaly, hypertension.

Fluid restriction - not recommended except in chronic oedematous states. Diuretics (e.g. frusemide) is not necessary in steroid responsive nephrotic syndrome but if required, use with caution as may precipitate hypovolaemia. Human albumin (20-25%) at 0.5 - 1.0 g/kg can be used in symptomatic grossly oedematous states together with IV frusemide at 1-2 mg/kg to produce a diuresis.

Definition Used for Nephrotic Syndrome

Remission proteinuria < 40mg/m2/H or urine albumin nil or trace for 3 consecutive days Relapse proteinuria > 40mg/m2/H or urine albumin 2+ or more for 3 consecutive days Frequent relapse 2 or more relapses within 6 months of initial response or 4 or more relapses within any 12 month period

Definition Used for Nephrotic Syndrome

Steroid dependence 2 consecutive relapses occurring during steroid taper or within 14 days of the cessation of steroids. Steroid sensitive NS normalization of proteinuria within 4 weeks after start of standard initial therapy with daily oral prednisolone Steroid Resistant failure to achieve remission in spite of 4 weeks of prednisolone 60mg/m2/day

Nephrotic Synd Definition Oedema Serum Alb <25g/L Proteinuria > 40 mg/m2/hr or urine protein creatinine ratio >200 mg/mmol Hypercholesterolaemia

Nephritic Synd Oedema Haematuria Hypertension Proteinuria (little) Uraemia Oliguria (<400ml/day) Azotaemia Inflammation of the glomeruli @ decreased kidney f(x) Increased hydrostatic pressure

Cause

Impaired protein reabsorption at proximal tubule @ increased glomerular permeability Decreased oncotic pressure

Cause of oedema

Referances
Nelson Textbook Of Paediatric 18th Ed. Handbook of hospital paediatric 2nd ed Paediatric Protocol 2nd ed