NEPHROTIC

SYNDROME
Nephrotic syndrome
is the clinical manifestation of glomerular diseases associated with heavy
(nephrotic-range) proteinuria.
defined as proteinuria >3.5 g/24 hr or a urine protein : creatinine ratio >2
triad of clinical findings associated with nephrotic syndrome arising
from the large urinary losses of protein are
Hypoalbuminemia (2.5 g/dL),
Edema, and
Hyperlipidemia (cholesterol >200 mg/dL).
Epidemiology and Prognosis
affects 1-3 per 100,000 children <16 yr of age
Without treatment, nephrotic syndrome in children is associated with a high
risk of death, most commonly from infections
80% of children with nephrotic syndrome respond to corticosteroid therap
Etiology
Most children with nephrotic syndrome have a form of primary or
idiopathic nephrotic syndrome (Table 527-1)
Glomerular lesions associated with idiopathic nephrotic syndrome:
Minimal change disease (the most common)
Focal segmental glomerulosclerosis
Membranoproliferative glomerulonephritis different age distribution
C3 glomerulopathy
Membranous nephropathy
May also be secondary to systemic diseases such as:
SLE
Henoch-Schnlein purpura
Malignancy (lymphoma and leukemia)
Infections (hepatitis, HIV, and malaria)
Pathogenesis:
Synthesis GF barrier
Permeability of glomelular
and repair to the
capillary wall
GBM proteins

Structural
MASSIVE proteinuria and support
hypoalbuminemia

Podocytes
(Foot Process)
Major impediments
to protein
Slit Diaphragm permeability across
glomelular
capillary wall
Podocytes
(Foot Process)
 Clinical Consequence
Edema
Underfill hypothesis
fall in the plasma protein level with a corresponding decrease in intravascular oncotic pressure.
leakage of plasma water into the interstitium EDEMA
reduced intravascular volume
increased secretion of vasopressin, atrial natriuretic factor, aldosterone
increased sodium and water retention

Overfill hypothesis
primary sodium retention, with subsequent volume expansion
leakage of excess fluid into the interstitium
epithelial sodium channel in the distal tubule may play a key role in sodium reabsorption in
nephrotic syndrome
The goal of therapy should be a gradual reduction of edema with judicioususe of diuretics,
sodium restriction, and cautious use of intravenous albumin infusions, if indicated.
Clinical Consequence
Hyperlipidemia
Increase in cholesterol
Triglycerides
Low-density lipoprotein
Very-low-density lipoproteins
Highdensity lipoprotein level remains unchanged or is low

Result of increased synthesis as well as decreased catabolism of lipids

 Clinical Consequence
Increase susceptibility to Infection
Hypoglobulinemia as a result of the urinary losses of immunoglobulin (Ig)G
Defects in the complement cascade from urinary loss of complement factors (predominantly C3
and C5), as well as alternative pathway factors B and D, lead to impaired opsonization of
microorganisms

susceptible to infections such as cellulitis, spontaneous bacterial peritonitis, and

bacteremia
significantly increased risk for infection with encapsulated bacteria (Pneumoccocal)
Spontaneous bacterial peritonitis presents with fever, abdominal pain, and peritoneal
signs
 Clinical Consequence
Hypercoagulability
Resulting from multiple factors:
Vascular stasis from hemoconcentration
Intravascular volume depletion
increased platelet number and aggregability
changes in coagulation factor levels

Increase in hepatic production of fibrinogen along with urinary losses of

antithrombotic factors such as antithrombin III and protein S
Deep venous thrombosis may occur in any venous bed, including the cerebral
venous sinus, renal vein, and pulmonary veins
Minimal change disease
Diagnostic Work-ups
Urinalysis
Proteinuria, microscopic hematuria
Hyaline, granular and cellular cast
Free lipids, doubly refractive bodies containing
cholesterol and fatty cast
Estimation of proteinuria by a timed urine
collection
> 40 mg/m2/hr or > 50 mg/kg/day or > 2 g/m2/day
Urine protein (mg/dl)/urine creatinine (mg/dl) of
> 3.5
Urine IgG to Transferrin ratio of < 0.1 suggest highly
selective proteinuria
 Blood urea nitrogen (BUN) and serum creatinine
Elevated in 25% of children (usually transient)

Serum electrolytes, serum total protein and albumin

Hypoalbuminemia 2.5 g/dl or less
Hypocalcemia

Serum cholesterol and triglycerides

 Anti-nuclear antibody
Serum complements C3, C4 ( or CH 50)
Antistreptolysisn O
Throat culture
Serologic tests for syphilis
Hepatitis B surface antigen
Renal biopsy
Management
MEDICAL
Corticosteroids
Cytotoxic drugs
Newer immunosuppressive drugs
pulse methylprednisolone
Corticosteroids
Drug of choice for inducing remission
Patients presenting for the first time can be
presumed to have MCNS
Several protocols have been published
INITIATION PHASE
daily for 4 weeks until remission followed by
MAINTENANCE PHASE
Give alternate day basis and discontinue after a slow
tapering total of 4 weeks
 Prednisone
60 mg/m2/day (max. 80 mg) for 4 weeks
60 mg/m2 every other day for 2 weeks
40 mg/m2 every other day for 2 weeks
20 mg/m2 every other day for 2 weeks
Then discontinue
IV pulse methylprednisolone 30 mg/kg every
other day for 3-6 doses with oral prednisone on
alternate days
 Indications:
Those who develop steroid toxicity due to prolonged use of these drugs
To induce prolonged remission in those who have frequent relapses
To induce remission in those who are unresponsive to steroid treatment

Drawback
Potential side effects and familys apprehension of risk involved

Dose
Cyclophosphamide: 2-2.5 mg/kg/day (cumulative dose 150 mg/kg) over 8-12
weeks
Chlorambucil: 0.1-0.2 mg/kg/day (7-10 mg/kg cumulative dose) over 8-10
weeks
CYTOTOXIC DRUGS
Cyclophosphamide
2-2.5 mg/kg/day for 8-12 weeks
Chlorambucil
0.1-0.2 mg/kg/day for 8-10 weeks

NOTE: with alternate day low dose steroid

Newer Immunosuppressive
Drugs
Aimed at altering immune response
Levamisole (antihelminthic drug) with T-cell
stimulating properties; may induce remission in
both steroid-responsive and steroid resistant
MCNS
Cyclosporine T-cell suppression properties,
beneficial in corticosteroid-resistant NS
IMMUNOREGULATORY DRUGS
Cyclosporine A
5 mg/kg/day in 2 doses orally for 6
months
Levamisole
2.5 mg/kg/day on alternate day for
1 year
Pulse Methylprednisolone
Therapy
IV alternate day dose of 30 mg/kg x 6 treatments then
Once weekly for 2 months
Alternate-day oral Prednisone ( 2 mg/kg/dose) is initiated after the
first course of IV methylprednisolone and is continued for 6 months
SUPPORTIVE MANAGEMENT
Diet and activity
No added salt diet
Fluid restriction may be prescribed
Adequate intake of high biologic-value
protein
Physical activity should not be
restricted
 Albumin infusion
Salt-poor albumin 0.5-1 g/kg over 1-2
hours followed by furosemide 1-2
mg/kg/dose
Fresh frozen plasma 10 ml/kg
cryosupernate
 Diuretics
Furosemide 1-2 mg/kg/dose
Thiazides and aldosterone inhibitors
have little effects
Non-pharmacologic methods like
standing in a water bath with the head
out
 Antibiotics
Antiplatelet drugs
Dipyridamole 5 mg/kg/day
NEPHRITIC
SYNROME
Nephritic syndrome
is the clinical ma
hematuria, edema, hypertension,
and moderate proteinuria nifestation of glomerular diseases associated with
Acute
Glomerulonephritis
 common in children w/ Group A -hemolytic streptococcal infections
classic example of the acute nephritic syndrome characterized by the
sudden onset of gross hematuria, edema, hypertension, and renal
insufficiency
most common glomerular causes of gross hematuria in children
ETIOLOGY AND EPIDEMIOLOGY
follows infection of the throat or skin by certain nephritogenic strains of
group A -hemolytic streptococci
97% of cases occur in less-developed countries
commonly follows streptococcal pharyngitis during cold-weather months
Streptococcal skin infections or pyoderma during warm-weather months
PATHOLOGY
Glomeruli appear enlarged and relatively bloodless and show diffuse
mesangial cell proliferation, with an increase in mesangial matrix
Polymorphonuclear leukocyte infiltration is common
Immunofluorescence microscopy reveals a pattern of lumpy-bumpy deposits
of immunoglobulin
On electron microscopy humps, are observed on the epithelial side of the
glomerular basement membrane
PATHOGENESIS
Circulating immune Streptococcal
complex antigens

Molecular mimicry

circulating antibodies react

with normal glomerular
antigens

in situ immune complex

formation
CLINICAL MANIFESTATIONS
The typical patient develops an acute nephritic syndrome 1-2 wk after an antecedent streptococcal
pharyngitis or 3-6 wk after a streptococcal pyoderma
Asymptomatic microscopic hematuria with normal renal function
gross hematuria with acute renal failure
Edema
Hypertension
Oliguria
risk for developing encephalopathy and/or heart failure secondary to hypertension or hypervolemia
Peripheral edema typically results from salt and water retention
The acute phase generally resolves within 6-8 wk
urinary
protein excretion and hypertension usually normalize by 4-6 wk after onset
persistent microscopic hematuria can persist for 1-2 yr after the initial presentation
DIAGNOSIS
Urinalysis demonstrates
red blood cells, often in association with red blood cell casts,
proteinuria, and
polymorphonuclear leukocytes

serum C3 level is significantly reduced in >90% of patients in the acute

phase returns to normal 6-8 wk after onset
Magnetic resonance imaging of the brain is indicated in patients with severe
neurologic symptoms and can demonstrate posterior reversible
encephalopathy syndrome in the parietooccipital areas on T2-weighted
images
 The clinical diagnosis of poststreptococcal GN is quite likely in a child
presenting with acute nephritic syndrome, evidence of recent streptococcal
infection, and a low C3 level.
Renal biopsy should be considered only in the presence of acute renal
failure, nephrotic syndrome, absence of evidence of streptococcal infection, or
normal complement levels.
PREVENTION and TREATMENT
Early systemic antibiotic therapy for streptococcal throat and skin infections
does not eliminate the risk of GN
10 day course of systemic antibiotic therapy with penicillin is recommended
to limit the spread of the nephritogenic organisms, antibiotic therapy does
not affect the natural history of APSGN
Sodium restriction, diuresis (usually with intravenous furosemide), and
pharmacotherapy with calcium channel antagonists, vasodilators, or
angiotensin-converting enzyme inhibitors, are standard therapies used to
treat hypertension