2. Learning objectives
• To define what nephrotic syndrome is
• Recognize the clinical and laboratory findings associated with minimal change
nephrotic syndrome.
• Plan the appropriate initial management of the first episode of minimal change
nephrotic syndrome.
• Formulate a differential diagnosis of nephrotic syndrome with and without
hematuria.
• Recognize complications associated with nephrotic syndrome.
• Understand the various factors that affect the prognosis of nephrotic syndrome.
3. Definition
• Nephrotic syndrome is the clinical manifestation
of glomerular diseases associated with heavy
proteinuria of >3.5 g/24 hr or a urine protein :
creatinine ratio >2.
• The triad of clinical findings associated with
nephrotic syndrome arising from the large
urinary losses of protein are:
– Hypoalbuminemia (≤2.5 g/dL)
– Edema
– Hyperlipidemia (cholesterol >200 mg/dL).
4. Epidemiology
• NS affects children of any age, from infancy to adolescence.
• Most common among school-aged children and adolescents
population.
• The prevalence worldwide is approximately 16 cases per 100,000
children, with an incidence of 2 to 7 per 100,000 children.
• Males are more affected than females at a ratio of 2:1 in children.
• Both sexes affected equally in adolescence.
5. Pathophysiology
• The underlying abnormality in nephrotic syndrome is an increased permeability of
the glomerular capillary wall, which leads to massive proteinuria and
hypoalbuminemia.
• The kidney uses a complex filtration system known as the glomerular filtration
barrier (GFB). It is composed of a glomerular basement membrane sandwiched
between a fenestrated endothelium and an epithelial layer made up of podocytes
and their foot processes, with interspersed filtration slits and slit diaphragm.
• The filtration barrier is charge and size specific, allowing water and small solutes to
pass through its pores into the urinary space.
• In nephrotic syndrome, there is an effacement of the podocyte foot processes that
can be seen on electron microscopy.
• Disruption of this barrier leads to the proteinuria seen in nephrotic syndrome.
6.
7. Pathogenesis-Edema
• Edema is the most common presenting
symptom of children with NS &Mechanism
not well understood.
• There are 2 opposing theories postulated, the
underfill hypothesis and the overfill
hypothesis.
8. The underfill hypothesis
• Nephrotic-range proteinuria leads to a fall in the
plasma protein level with decrease in intravascular
oncotic pressure.
• This leads to leakage of plasma water into the
interstitium, generating edema.
• Reduced intravascular volume causes increased
secretion of vasopressin and atrial natriuretic factor,
which, along with aldosterone, result in increased
sodium and water retention by the tubules.
9. Overfill theory
• Primary sodium retention that is directly
induced by the renal disease ( overfill
hypothesis).
10. Pathogenesis…
• Hyperlipidemia: Due to increased synthesis as
well as decreased catabolism of lipids.
• Infections: Increased Susceptibility to Infections
such as cellulitis, spontaneous bacterial
peritonitis, and bacteremia due to increased
urinary losses of immunoglobulin, C3, factor B, D.
• Children with NS are at significantly increased risk
for infection with encapsulated bacteria
especially pneumococcal disease
11. Pathogenesis…
• Nephrotic syndrome is a hypercoagulable
state resulting from:
– Vascular stasis from hemoconcentration and
intravascular volume depletion
– Increased platelet number and aggregability,
– There is an increase in hepatic production of
fibrinogen along with urinary losses of
antithrombotic
12. Classification of NS
• Primary( Idiopathic): Refers to that which is not associated with
another identifiable systemic disease. Idiopathic nephrotic
syndrome can be further subdivided based on histologic
information gathered via percutaneous renal biopsy.
– The 3 major subgroups are MCNS (also known as minimal change
disease), FSGS, and membranous nephropathy (MN). MCNS is the
most common form of nephrotic syndrome in school-aged children.
• Secondary: Results from systemic diseases such as Schönlein
purpura, malignancy, and infections (hepatitis, HIV, and malaria).
• Hereditary: Results from genetic mutations that lead to defects in
various regions of the glomerular filtration barrier;
13. Minimal Change NS
• More common in boys than girls in a ration of
2 : 1
• Appears between the ages of 2 and 6 yrs
• Most common type of NS in 85-90% of
patients <6 yrs.
• Rare in adolescents population (20-30%).
14. Clinical presentation-MCNS
• The classic presentation is a child between the
ages of 3 and 9 years with:
• Gravity dependent edema.
• Onset may follow URTI.
15. Mesangial proliferation
• Characterized by a diffuse increase in mesangial cells and
matrix on light microscopy.
• Immunofluorescence microscopy might reveal trace to 1+
mesangial IgM and/or IgA staining.
• Electron microscopy reveals increased numbers of
mesangial cells and matrix as well as effacement of the
epithelial cell foot processes.
• Approximately 50% of patients with this histologic lesion
respond to corticosteroid therapy.
16. Focal segmental glomerulosclerosis
• Glomeruli show lesions that are both focal.
• Lesions consist of mesangial cell proliferation segmental scarring on light
microscopy.
• Immunofluorescence microscopy is positive for IgM and C3 staining in the
areas of segmental sclerosis.
• Electron microscopy demonstrates segmental scarring of the glomerular
tuft with obliteration of the glomerular capillary lumen.
• Only 20% of patients with FSGS respond to prednisone.
• The disease is often progressive, ultimately involving all glomeruli, and
ultimately leads to end-stage renal disease in most patients.
17. Diagnosis
• The urinalysis reveals 3+ or 4+ proteinuria,
• Microscopic hematuria in 20% of children.
• A spot urine protein : creatinine ratio should be >2.0.
• The serum creatinine value is usually normal.
• The serum albumin level is <2.5 g/dL,
• Elevated serum cholesterol and triglyceride levels.
• Serum complement levels are normal.
• A renal biopsy is not routinely performed if the patient
fits the standard clinical picture of MCNS.
• Serum electrolytes are generally normal
18. Indication for renal biopsy
• Children with features that make MCNS less
likely:
– Gross hematuria
– Hypertension
– Renal insufficiency
– Hypocomplementemia
– Age <1 yr or >12 yr).
19. Treatment of Initial Episode of NS
• Prednisolone as a single daily dose of 60 mg/m2/day
or 2 mg/kg/day for 4-6 weeks.
• Followed by alternate-day prednisone 40 mg/m2 od or
1.5 mg/kg od for 8 wk to 5 mo, with tapering of the
dose and eventually discontinue in 1-2 mo.
• 25% albumin -significant generalized edema with
evidence of intravascular volume depletion
• Frusemide-Volume overload with hypertension
22. Prognosis
• Approximately 80-90% of children respond to
steroid therapy.
• Response is defined as the attainment of
remission within the initial 4 wk of
corticosteroid therapy.
• Remission consists of a urine protein :
creatinine ratio of <0.2 or <1+ protein on urine
dipstick for 3 consecutive days.
23. Complications of NS
• Edema. If severe & symptomatic(large pleural
effusions, ascites, or severe genital edema)
manage as follows:
– Admit
– Sodium restriction
– Water & fluid restriction
– Loop diuretics
– IV 25% albumin for generalized edema with
intravascular volume depletion.
24. Complications
• Dyslipidemia
– Managed with a low-fat diet.
• Immunizations.
– Pneumococcal vaccination with the 13-valent conjugant vaccine and
23-valent polysaccharide vaccine & influenza vaccination annually.
– Defer vaccination with live vaccines until the prednisone dose is
– below either 1 mg/kg daily or 2 mg/kg on alternate days.
– Live virus vaccines are contraindicated in children receiving
corticosteroidsparing agents such as cyclophosphamide or
cyclosporine
