This document discusses nephrotic syndrome in children. It defines nephrotic syndrome as having proteinuria >3.5g/24hr or a urine protein to creatinine ratio >2. It most commonly presents with edema, hypoalbuminemia, and hyperlipidemia. The majority of cases are idiopathic and minimal change disease is the most common pathology. Treatment involves corticosteroids, which are effective in 80% of children. Relapses may occur and persistent disease may require additional immunosuppressive therapies. Management also includes treating infections, hyperlipidemia, thrombosis, and growth issues associated with long-term steroid use.

1. Dr. Shami Pokhrel
MD. Pediatrics

2.  It is a clinical manifestation of glomerular disease
 Proteinuria >3.5g/24hr
 Urine protein: creatinine ratio >2

3. TRIAD
1. Large urinary losses of protein causing
hypoalbuminemia (< or equal to 2.5g/dl)
2. Edema
3. Hyperlipidemia (>200mg/dl)

4.  Affects 1-3 per 100,000 children < 16 years of
age
 80% respond to corticosteroid therapy
 There is no differentiation between ethics while
MCNS incidence is higher in males

5.  Most of the nephrotic syndrome have a form of
a primary or idiopathic nephrotic syndrome
 Idopathic cases can have various underlying
pathology like minimal change disease (the
most common), focal segmental
glomerulosclerosis, membranoproliferative
glomerulonephritis, C3 glomerulopathy and
membranous nephropathy.

6. Nephrotic syndrome may also be secondary
to systemic diseases such as SLE, HSP,
malignancy (lymphoma and leukemia), and
infections ( hepatitis, HIV, and malaria)
A number of hereditary proteinuria
syndromes are ca used by mutations in genes
that encode critical protein components of
the glomerular filtration apparatus

7.  Role of podocyte
 The underlying abnormality is an increased
permeability of the glomerular capillary wall,
which leads to massive proteinuria.
 The podocytes plays a crucial role in the
development of proteinuria and progression of
glomerulosclerosis

8.  Foot processes are the extension of podocytes
that terminate on the GBM.
 The foot processes of the podocytes
interdigitate with those from adjacent
podocytes and are connected by a slit called the
slit diaphragm.
 The podocyte functions as structural support of
the capillary loop.

9.  Podocytes are the major component of the
glomerular filtration barrier to proteins, and is
involved in synthesis and repair of the GBM
 Slit diaphragm is one of the major impediments
to proteins permeability across the glomerular
capillary wall

10.  Important component proteins of the slit
diaphragm include nephrin, podocin, and
alpha-actin4
 Any injury to the podocyte or genetic
mutations of genes producing podocyte
proteins may cause nephrotic-range proteinuria

11.  In idopathic, hereditary, and secondary forms
of nephrotic syndrome, there are immune and
non-immune insults to the podocyte that lead to
1. foot process effacement of the podocyte
2. A decrease in number of functional podocytes
3. Altered slit diaphragm integrity

12.  Edema: the most common presenting symptom
in children with nephrotic syndrome
1. Underfill hypothesis
2. Overfill hypothesis

13.  Hyperlipidemia
1. It is thought to be the result of increased
synthesis as well as decreased catabolism of
lipids
2. There has been found to be an increase in
cholesterol, triglycerides, low-density
lipoprotein, and very low density
lipoproteins. The high density lipoprotein
level remains unchanged or is low

14.  Increased susceptibility to infections
1. Cellulitis
2. Spontaneous bacterial peritonitis
3. Bacteremia
 Reason is because of hypoglobulinemia, loss
of C3, C5. Hence, they are at risk for
infection with encapsulated bacteria like
pneumococcus

15.  Hypercoagulability
1. Vascular stasis from hemoconcentration and
intravascular volume depletion, increased
platelet number and aggregability, and
changes in coagulation factor levels.
2. Increased hepatic production of fibrinogen
along with urinary losses of antithrombotic
factors such as antithrombin III and protein S.

16.  It accounts for 90% cases of nephrotic syndrome
 Renal biopsy does not show significant abnormalities
on light microscopy
 Electron microscopy shows obliteration of epithelial
cell foot processes, which is not specicfic
 Immunofluorescence studies do not show any deposits,
except in a small proportion, where mesangial deposits
of IgM may be present

17.  Typical presentation is an insidious onset of
swelling starting first from peri-orbital edema
progressing then to legs
 Edema is pitting edema
 Gradually edema may become generalized with
ascites, hydrothorax and hydrocele
 As edema worsens urine output decreases

18.  Blood pressure is usually normal. Sustained
elevation suggests the possibility of significant
glomerular lesions
 Severe muscle wasting underlies the
misleading relatively bloated and well-looking
child
 Infections may be present at the onset and
during relapses

19.  Urine examination shows heavy protienuria
(3+ or 4+)
 24 hr urinary protein excretion
 A spot urinary protein: creatinine ratio>2
 Gorss hematuria or persistent microscopic
hematuria suggests the likelihood of significant
glomerular lesions.

20.  Blood levels of IgG are low and those of IgM
elevated
 C3 level is normal
 Hypercholesterolemia
 Renal insufficiency

21.  Hyaline and granular casts may be present
 Low serum albumin values (<2.5g/dl)
 Renal biopsy recommended in children with
atypical presentation (age onset <1 yr or over
10yrs), persistent hematuria, low C3 level,
hypertension or impaired renal function

22.  Single daily dose of 60mg/m2/day or
2mg/kg/day of prednisolone for 4-6 weeks
followed by alternate day of 40mg/m2/day or
1.5mg/kg/day for a period ranging from 8wk –
5 months, with tapering of dosage
 Side effects of the drug must be explained

23.  Approximately 80-90% of children respond to
steroid therapy
 Response: attainment of remission within the
initial 4 wk of corticosteroid therapy
 Remission: consists of urine protein:creatinine
ratio of <0.2 or <1+ protein on urine dipstick for 3
consecutive days.
 The vast majority of children who respond to
prednisone therapy do so within the first 5 wk of
treatment

24.  The child should receive a high protein diet
 No extra salt is given
 Associated infection treated
 Tuberbulosis is ruled out
 Judicious use of diuretics
 Rapid fluid loss should not be attempted

25.  Edema : severe symptomatic edema needs
hospitalization such as pleural effusions,
ascites, or severe genital edema
 Diuretics may be used but with extreme
caution as patient may be in intravascular
volume depletion although he or she may look
edematous

26.  25% albumin may be infused followed by
furosemide (1-2mg/kg/dose) whenever patient
has severe edema with evidence of
intravascular volume depletion eg.,
hemoconcentration, hypotension, tachycardia.
 Such therapy mandates monitoring of blood
pressure, volume status, renal function,
electrolyte homeostasis. Rapid infusion of
albumin may lead to volume overload, with
hypertension, heart failure, and pulmonary
edema

27.  Dyslipidemia: It should be managed with low-
fat diet. Dietary fat intake should be limited to
<30% of calories with saturated fat intake
<10% calories.
 Dietary cholesterol intake should be
<300mg/day. There are insufficient data to
suggest the use of HMG-CoA reductase
inhibitors in children with dyslipidemia

28.  Infections: Families of child with nephrotic
syndrome must be counseled regarding the signs
and symptoms of infections such as cellulitis,
peritonitis, and bacteremia.
 Suspicion of infection should prompt to send blood
cultures before starting empiric antibiotic therapy
that covers mainly pneumococcal and gram
negative organisms

29.  Thromboembolism: children with clinical signs
of thromboembolism should be evaluated by
appropriate imaging studies to confirm the
presence of a clot
 Heparin, low-molecular-weight heparin, and
warfarin are therapeutic options

30.  Obesity and growth: steroids may increase BMI
in children who are overweight when therapy is
initiated, and these children are more likely to
remain overweight.
 Anticipatory dietary counseling is recommended.
Growth may be affected in children who require
long-term steroid therapy. Steriod-sparing
strategies may improve linear growth in children
who require prolonged courses of steroids

31.  Relapse of nephrotic syndrome: it is defined as
the urine protein : creatinine ratio of >2 or > or
equal to 3+ protein on urine dipstick testing for 3
consecutive days.
 Relapses are treated in a manner similar to initial
episode, except that daily prednisone courses are
shortened. Daily high-dose prednisone is given
until the child had achieved remission, and the
regimen is then switched to alternate-day therapy.

32.  Steroid resistance: failure to achieve remission
after 8 wks of corticosteroid therapy. These
children need renal biopsy, evaluation of kidney
function and quantitation of urine protein in
addition to urine dipstick testing.
 Cause of steroid resistant NS is usually caused by
FSGN (80%), MCNS, or membranoproliferative
glomerulonephritis.

33.  Candidates are steroid-dependent patients
frequent relapsers, and steroid-resistant
patients.
 Candidates who have severe corticosteroid
toxicity

34.  Cylcophosphamide
 Calcineurin inhibitors (cyclosporin or tacrolimus)
 Mycophenolate
 Levamisole
 Rituximab
 Angiotensin-converting enzyme inhibitors and
angiotensin II receptor blockers may be helpful in
adjunct therapy to reduce proteinuria in steroid-
resistant patients

35.  Full pneumococcal vaccine and influenza vaccine
annually to the patient and their household
contacts
 Defer vaccination with live vaccines until the
prednisone dose is below either 1mg/kg daily or
2mg/kg on alternate day
 Live vaccine is contraindicated in those receiving
corticosteroid-sparing agents

36.  Following close contact with varicella infection
children under immunosuppresive drugs must be
given varicella-zoster immunoglobulin
 Immuninze healthy household contacts with live
vaccines to minimize the risk of transfer of
infection to patients but avoid direct exposure of
the child to gastrointestinal or respiratory
secretions of vaccinated contacts for 3-6 wk after
vaccination

37.  NS can occur as a secondary feature of many forms of
glomerular disease
 Secondary nephrotic syndrome should be suspected in
patient >8 yrs and those with hypertension, hematuria,
renal dysfunction, extrarenal symptoms or depressed
serum complement levels
 Malaria and schistosomiasis are the leading cause of NS
in areas where these diseases are endemic

38.  Lymphomas
 Drugs (penicillamine, captopril, gold, NSAIDS,
mercury compounds can resemble membranous
glomerulopathy), MCNS (probenecid,
ethosuximide, methimazole, chlorpropamide,
phenytoin, trimethadone, paramethadone).

39.  NS has a poor prognosis when it occurs in the first
year of life
 Manifest at birth or within first 3 months of age
 Can be primary or secondary to number of etiologies
such as in utero infections (cytomegalovirus,
toxoplasmosis, syphilis, hepatitis B and C, HIV),
infantile systemic lupus erythematosus, or mercury
exposure

40.  Infants with primary NS are typically born with an
enlarged placenta (>25% of infants weight). Prenatal
diagnosis can be made by the presence of elevated
maternal and amniotic alpha-fetoprotein levels