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NEPHROTIC
SYNDROME
02/03/2024 Abel W(MD)
Outline
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Introduction
Causes
Idiopathic Nephrotic Syndrome
• Congenital nephrotic syndrome is defined as NS
manifesting at birth or within the first 3 mo of life.
• Congenital nephrotic syndrome may be classified as
• Primary or as secondary to a number of etiologies
such as in-utero infections (CMV, toxoplasmosis,
syphilis, hepatitis B and C, HIV), infantile SLE, or
mercury exposure. 02/03/2024
Introduction
Nephrotic syndrome, a manifestation of
glomerular disease, is Xized by
Nephrotic range proteinuria (> 40 mg/m2/hr or
+3 or +4 dipstick or a first morning protein :
creatinine ratio of >2-3 : 1),
Hypoalbuminemia (serum albumin <3gm/dl),
Edema (anasarca), and
Hyperlipidemia ( > 200gm/dl).
Serum cholesterol and triglyceride levels are
elevated. 02/03/2024
PATHOPHYSIOLOGY
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1. Causes of proteinuria
Abnormal permeability of the
glomerular capillary BM to plasma
protein.
Protein loss exceeds 40mg/m²/hr in
children and >3.5 gm/24hr in adults
It is primarily composed of albumin.
Edema appears when serum albumin
falls below 2.5g/dl.
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Cont’d
2. Mechanism of edema
Initiated by hypoalbuminemia.
Hypoalbuminemia decreased plasma oncotic
pressure transudation of fluid from Intravascular
compartment to interstitial space.
Decreased IV volume dec. renal perfusion
pressure activation of RAAS increase in
distal tubular reabsorption of sodium.
Dec. IV volume stimulate the release of ADH
increase reabsorption of water in02/03/2024
collecting duct.
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3. Mechanism of hyperlipidemia
a. The hypoproteinemia stimulate
generalized protein synthesis in the liver
including lipoproteins.
b. Reduced lipid catabolism due to reduced
level of lipoprotein lipase (loss in urine)
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Introduction
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Approximately 90% of children with nephrotic
syndrome have idiopathic or primary NS.
Idiopathic NS is associated with primary glomerular
disease without evidence of a specific systemic cause.
Glomerular lesions associated with idiopathic nephrotic
syndrome include
Minimal change disease (the most common),
Focal segmental glomerulosclerosis,
Membranoproliferative glomerulonephritis,
Membranous nephropathy and
Diffuse mesangial proliferation.
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Introduction
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Nephrotic syndrome may also be secondary to systemic
diseases such as
Systemic lupus erythematosus,
Henoch-Schonlein purpura,
Malignancy (lymphoma and leukemia),
Infections (hepatitis, HIV, and malaria) and
Drugs like Penicillamine.
A number of hereditary proteinuria syndromes are
caused by mutations in genes that encode critical protein
components of the glomerular filtration apparatus.
Example, Finnish-type congenital nephrotic
syndrome (absence of nephrin) 02/03/2024
Idiopathic Nephrotic Syndrome
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Idiopathic nephrotic syndrome is the most common
form of childhood nephrotic syndrome, representing
>90 % of cases between 1 and 10 years of age and 50
% after 10 years of age.
Idiopathic nephrotic syndrome is defined by the
association of the clinical features of nephrotic
syndrome with renal biopsy findings of diffuse foot
process effacement on electron microscopy and
minimal changes (called minimal change disease
[MCD]), primary focal segmental glomerulosclerosis
(FSGS), or mesangial proliferation on light
microscopy. 02/03/2024
Idiopathic Nephrotic Syndrome
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In minimal change nephrotic syndrome
(MCNS) (about 85% of total cases of nephrotic
syndrome in children),
the glomeruli appear normal or show a minimal
increase in mesangial cells and matrix.
Findings on immunofluorescence microscopy are
typically negative, and electron microscopy simply
reveals effacement of the epithelial cell foot processes.
More than 95% of children with MCD respond to
corticosteroid therapy.
02/03/2024
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Mesangial proliferation
is xrized 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. 02/03/2024
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In FSGS, glomeruli show lesions that are both focal (present
only in a proportion of glomeruli) and segmental (localized
to ≥1 intraglomerular tufts).
The 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.
E/M demonstrates segmental scarring of the glomerular tuft with
obliteration of the glomerular capillary lumen.
Similar lesions may be seen 2O to HIV infection, vesicoureteral
reflux, and intravenous use of heroin and other drugs of abuse.
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.
02/03/2024
Idiopathic Nephrotic Syndrome
Clinical Manifestations:
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The idiopathic nephrotic syndrome is more
common in boys than in girls (2 : 1) and most
commonly appears between the ages of 2 and 6 yr.
MCNS is present in 85-90% of patients <6 yr of
age.
In contrast, only 20-30% of adolescents who
present for the first time with nephrotic
syndrome have MCNS.
The more common cause of idiopathic nephrotic
syndrome in this older age group is FSGS.
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Idiopathic Nephrotic Syndrome
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Children usually present with mild edema, which is
initially noted around the eyes and in the lower
extremities. Periorbital swelling that decreases
throughout the day.
With time, the edema becomes generalized, with the
dev’t of ascites, pleural effusions, and genital edema.
Anorexia , abdominal Pain and diarrhea are
common.
Important features of minimal change idiopathic
nephrotic syndrome are the absence of
hypertension and gross hematuria.
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Idiopathic Nephrotic Syndrome
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Children with features that make MCNS less
likely:
Gross hematuria
Hypertension
Renal insufficiency
Hypocomplementemia
Age (<1 yr or >8 yr)
Renal biopsy should be considered before
treatment.
02/03/2024
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The D/Dx of the child with marked edema
includes protein-losing enteropathy, hepatic
failure, heart failure, acute or chronic
glomerulonephritis, and protein
malnutrition.
A diagnosis other than MCNS should be
considered in children <1 yr of age, a positive
family history of NS, presence of extrarenal
findings (e.g., arthritis, rash, anemia), HTN or
pulmonary edema, acute or chronic 02/03/2024
renal
Idiopathic Nephrotic Syndrome Diagnosis:
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The urinalysis reveals 3+ or 4+ proteinuria.
A spot urine protein:creatinine ratio exceeds
2.0, and urinary protein excretion exceeds 40
mg/m2/hr.
The serum albumin level is <2.5 g/dL.
Serum cholesterol and triglyceride levels are
elevated.
Serum complement levels are normal.
The serum creatinine value is usually
02/03/2024
Idiopathic Nephrotic Syndrome Treatment:
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The pathophysiology and Rx of NS must be
carefully reviewed with the family to enhance
understanding of their child's disease.
Children with severe symptomatic edema,
including large pleural effusions, ascites, or
severe genital edema, should be
hospitalized.
Children with their first episode of
nephrotic syndrome and mild to moderate
edema may be managed as outpatients.
02/03/2024
Idiopathic Nephrotic Syndrome
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Children with onset of uncomplicated nephrotic
syndrome between 1 and 8 yr of age are likely to
have steroid-responsive MCNS, and steroid therapy
may be initiated without a diagnostic renal biopsy.
Dose of prednisone 60 mg/m2/day (maximum daily
dose, 80 mg) in a single daily dose for 4-6
consecutive wk.
After the initial 6-wk course, the prednisone dose
should be tapered to 40 mg/m2/day given every other
day as a single daily dose for at least 4 wk.
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Idiopathic Nephrotic Syndrome
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The alternate-day dose is then slowly tapered
and discontinued over the next 1-2 mo.
The vast majority of children who respond
to prednisone therapy do so within the first
5 wk of treatment.
About 80-90% of children respond to steroid
therapy (clinical remission, diuresis, and urine
trace or negative for protein for 3 consecutive
days) within 3 wk.
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Idiopathic Nephrotic Syndrome
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Children with severe symptomatic edema, Sodium
restriction, fluid restriction may be necessary if
the child is hyponatremic.
A swollen scrotum may be elevated with pillows to
enhance fluid removal by gravity.
Diuresis may be augmented by the administration
of loop diuretics (furosemide), orally or
intravenously, although extreme caution should be
exercised. Aggressive diuresis can lead to
intravascular volume depletion and a significantly
increased risk of intravascular thrombosis.
02/03/2024
Outcome based upon steroid response:
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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.
A subset of patients relapse while on alternate-day
steroid therapy or within 28 days of completing a
successful course of prednisone therapy. Such
patients are termed steroid dependent.
Patients who respond well to prednisone therapy
but relapse ≥4 times in a 12-mo period are termed
frequent relapsers. 02/03/2024
Idiopathic Nephrotic Syndrome
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Complications:
Infection is a major complication of
nephrotic syndrome.
Factors for recurrent infection
Urinary losses of Igs and properdin factor B
that opsonize certain bacteria.
Defective cell-mediated immunity
Immunosuppressive therapy
Malnutrition, and edema or ascites acting as a
potential culture medium. 02/03/2024
Idiopathic Nephrotic Syndrome
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Spontaneous bacterial peritonitis is a common
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.
A high index of suspicion for bacterial peritonitis,
prompt evaluation (including cultures of blood
and peritoneal fluid), and early initiation of
antibiotic therapy are critical. 02/03/2024
Idiopathic Nephrotic Syndrome
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Increased risk of thromboembolic events.
Both arterial and venous thromboses may be seen, including
renal vein thrombosis, pulmonary embolus, sagittal sinus
thrombosis, and thrombosis of indwelling arterial and venous
catheters.
The risk of thrombosis is related to increased prothrombotic
factors (fibrinogen, thrombocytosis, hemoconcentration,
relative immobilization) and decreased fibrinolytic factors
(urinary losses of antithrombin III, proteins C and S), increased
plasma platelet production (as an acute phase reactant),
Hyperlipidemia, particularly in patients with complicated
nephrotic syndrome, may be a risk factor for cardiovascular
disease; myocardial infarction. 02/03/2024
Idiopathic Nephrotic Syndrome Prognosis:
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Most children with steroid-responsive NS
have repeated relapses, which generally
decrease in frequency as the child grows
older.
Children who respond rapidly to steroids and those
who have no relapses during the first 6 mo after
diagnosis are likely to follow an infrequently
relapsing course.
The child with steroid-responsive nephrotic
syndrome is unlikely to develop chronic kidney
disease, that the disease is rarely hereditary.
02/03/2024
Idiopathic Nephrotic Syndrome
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More than 95% of children with minimal
change disease respond to corticosteroid
therapy.
Approximately 50% of patients with
Mesangial proliferation respond to
corticosteroid therapy.
Only 20% of patients with FSGS respond to
prednisone.
02/03/2024
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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 ESRD
requiring dialysis or kidney
transplantation.
Recurrent nephrotic syndrome develops in
30-50% of transplant recipients with FSGS.
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Thank you
02/03/2024
