Nephrotic syndrome is a kidney disorder characterized by heavy proteinuria, low albumin levels, edema, and high cholesterol. The most common type in children is minimal change nephrotic syndrome, which is idiopathic and affects boys more than girls aged 2-6 years. Treatment involves high-dose steroids to induce remission, followed by lower alternate-day doses for maintenance. Complications include edema, dyslipidemia, and increased infection risk. With treatment, 80-90% of children experience remission of symptoms.

1. Nephrotic Syndrome
Dr. Franceska Akello

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.

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

21. Alternative treatment
• Meant for –
– Steroid-dependent patients
– Frequent relapsers
– Steroid-resistant
– Corticosteroid toxicity (cushingoid appearance,
hypertension, cataracts, and/or growth failure).
• Drugs used include:
– Cyclophosphamide
– Cyclosporin, tacrolimus
– Levamisole
– Mycophenolate morfetil

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