Nephrotic syndrome
By Dr Misikir Ambaye (MD, Pediatrician)
• Primarily a pediatric disorder and is 15 times
more common in children than adults.
• The incidence is 2-3/100,000 children per
year; and the majority of affected children will
have steroid-sensitive minimal change disease.
The characteristic features of nephrotic
syndrome are-
Heavy proteinuria (>3.5 g/24 hr in adults or
40 mg/m2/hr in children or urine protein to
creatinine ratio >2)
Hypoalbuminemia (<2.5 g/dL),
Edema
Hyperlipidemia ( Cholesterol>200 mg/dl)
PATHOPHYSIOLOGY
• Increased glomerular capillary
permeability→massive
proteinuria→hypoalbuminemia→↓sed plasma
oncotic pressure→transudation of fluid from
intravascular compartment to the
interstitium.→edema formation.
• ↑sed serum level of lipids is due to increased
synthesis of lipoproteins by the liver and increased
loss of lipoprotein lipase in the urine→↓sed lipid
catabolism.
The role of podocytes
• The podocyte functions as structural support of the capillary loop.
It is a major component of the glomerular filtration barrier to
proteins
• The slit diaphragm is one of the major impediments to protein
permeability across the glomerular capillary wall.
• Slit diaphragms are not simple passive filters—they consist of
numerous proteins like nephrin,podocin,CD2AP, and α-actinin 4
that play an important role in podocyte function
• Podocyte injury or genetic mutations of genes producing
podocyte proteins may cause nephrotic-range proteinuria
The role of immune system
• Minimal change nephrotic syndrome (MCNS) may occur
after viral infections and allergen challenges
• MCNS has also been found to occur in children with
Hodgkin lymphoma and T-cell lymphoma
• Immunosuppression occurs with drugs such as
corticosteroids and cyclosporine
Classification
1. Idiopathic nephrotic syndrome -90%
Minimal change disease (MCD)
Focal segmental glomerulosclerosis (FSGS)
Mesangial proliferation
2. Secondary nephrotic syndrome (systemic)-
10%
SLE,HSP,malignancies
Infections
CLINICAL MANIFESTATIONS
• The idiopathic nephrotic syndrome is more common in
males than in females (2:1) and most commonly
appears between the ages of 2 and 6 yr. It has been
reported as early as 6 mo .Children usually present with
mild edema, which is initially noted around the eyes
and in the lower extremities.
• With time, the edema becomes generalized, with the
development of ascites, pleural effusions, and genital
edema. Anorexia, irritability, abdominal pain, and
diarrhea are common; hypertension and gross
hematuria are uncommon.
Differential diagnosis
• PROTEIN LOSING ENTEROPATHY
• HEPATIC FAILURE
• CONGESTIVE HEART FAILURE
• ACUTE OR CHRONIC GLOMERULONEPHRITIS
• PROTEIN ENERGY MALNUTRITION
DIAGNOSIS
• The urinalysis reveals 3+ or 4+ proteinuria;
microscopic hematuria may be present in 20%
urinary protein excretion exceeds 3.5 g/24 hr in
adults and 40 mg/m2/hr in children.
• The serum creatinine value is usually normal,
but it may be increased because of diminished
renal perfusion resulting from contraction of
the intravascular volume.
• The serum albumin level is generally <2.5 g/dL,
and the serum cholesterol and triglyceride
levels are elevated.
• C3 and C4 levels are normal.
• Renal biopsy is not required for diagnosis in
most children.
Indications for biopsy are
• Hematuria
• Hypertension
• Renal insufficiency
• Hypocomplementemia
• age<1yr or>8yr
• Secondary nephrotic syndrome should be
suspected in patients
>8 yr
hypertension
hematuria, renal dysfunction,
extrarenal symptoms (rash,arthralgia,fever)
Depressed serum complement levels.
TREATMENT
• Children with severe symptomatic edema, including
large pleural effusions, ascites, or severe genital
edema, should be hospitalized.
• In addition to sodium restriction, fluid restriction
may be necessary if the child is hyponatremic. A
swollen scrotum may be elevated with pillows to
enhance the removal of fluid by gravity. Diuresis may
be augmented by administration of chlorothiazide
(10 mg/kg/dose IV every 12 hr) or metolazone (0.1
mg/kg/dose PO bid) followed by furosemide 30 min
later (1–2 mg/kg/dose IV q 12 hr).
TREATMENT
• Children having the first episode of nephrotic
syndrome and mild to moderate edema may
be managed as outpatients
• Sodium intake should be reduced by the
initiation of a low-sodium diet and may be
normalized when the child enters remission.
• Such therapy mandates close monitoring of
volume status, serum electrolyte balance, and
renal function.
• In children with presumed MCNS, prednisone
should be administered at a dose of 60
mg/m2/day (maximum daily dose, 80 mg
divided into 2–3 doses) for at least 4
consecutive weeks .
• Remission is defined by proteinuria of trace or
negative for 3 consecutive days
• After the initial 6-wk course, the prednisone
dose should be tapered to 40 mg/m2/day given
every other day as a single morning dose. The
alternate-day dose is then slowly tapered and
discontinued over the next 2–3 mo
• Children who continue to have proteinuria
(2+ or greater) after 8 wk of steroid therapy
are considered steroid resistant, and a
diagnostic renal biopsy should be performed
• Patients who respond well to prednisone
therapy but relapse ≥4 times in a 12-mo period
are termed frequent relapsers.
• Children who fail to respond to prednisone
therapy within 8 wk are termed steroid resistant
• A subset of patients will relapse while on
alternate-day steroid therapy or within 28
days of stopping prednisone therapy. Such
patients are termed steroid dependent
• Steroid-dependent patients, frequent relapsers,
and steroid-resistant patients may be candidates
for alternative agents, particularly if the child
suffers severe corticosteroid toxicity (cushingoid
appearance, hypertension, cataracts, and/or
growth failure).
• Cyclophosphamide prolongs the duration of
remission and reduces the number of relapses in
children with frequently relapsing and steroid-
dependent nephrotic syndrome
COMPLICATIONS
• Infection- due to urinary losses of immunoglobulins and properdin
factor B, defective cell-mediated immunity, immunosuppressive
therapy, malnutrition, and edema/ascites acting as a potential
“culture medium
• Spontaneous bacterial peritonitis is the most frequent type of
infection, although sepsis, pneumonia, cellulitis, and urinary tract
infections may also be seen.
• Although Streptococcus pneumoniae is the most common
organism causing peritonitis, gram-negative bacteria such as
Escherichia coli may also be encountered
• Children with nephrotic syndrome are also at
increased risk of thromboembolic events. The
incidence of this complication in children is 2–
5%.
• Hyperlipidemia-risk for cardiovascular disease
e.g myocardial infarction.
PROGNOSIS
• The majority of children with steroid-responsive
nephrotic syndrome have repeated relapses,
which generally decrease in frequency as the
child grows older.
• Children with steroid-resistant nephrotic
syndrome, most often caused by FSGS, generally
have a much poorer prognosis.
• These children develop progressive renal
insufficiency, ultimately leading to end-stage renal
disease requiring dialysis or renal transplantation.
THANK
YOU
