LECTURE NEPHROTIC SYNDROME.pdf

Dr. Reyad Ahmed Abdu Mansoor
consultant pediatrician in university of Science & Technology Hospital ,
consultant pediatrician . in Al-sabeen Hospital
Associated Member Of The Arabic Board
1/19/2010 Dr. Reyad Ahmed Abdu Mansoor 1

 DEFINITION OF NS
 EPIDEMIOLOGY
 CLASSIFICATION OF NS
 PATHOPHYSIOLOGY OF NS
 CLINICAL MANIFESTATION OF NS
 COMPLICATION OF NS
 DIFFERENTIAL DIAGNOSIS (EDEMA)
 INVESTIGATIONS
 MANAGEMENT
 MANAGEMENT
 MONITORING
 STEROID THERAPY (SPECIFIC)
 Steroid – Sensitive NS
 COURSE OF DISEASE
 Steroid – Resistant NS
 GENERAL THERAPY (NON- SPECIFIC)
 PROGNOSIS
 APPROACH TO A CHILD WITH PROTEINURIA

 Physical examination
 Vital signs  normal
history
A 3-year-old boy who present to the pediatric clinic with a 2-day history of puffy eyes.
Past medical history
History of atopy and allergic disease
Drug history
No medication
Family history
His mother suffers from asthma
1. What is the diagnosis?
2. What other investigations should to be performed at presentation?
3. What is the treatment?
 Vital signs  normal
 Anthropometric measures  normal
 Systemic examination
 He is alert and cooperative during examination
 No respiratory signs
 Has puffy eyes
 Scrotal edema
 Pitting pedal edema
 No abdominal distension

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Normal protein excretion
Defined as ≤ 4 mg/m2/hr
Urine-pr/urin-creatine
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Abnormal protein excretion
Defined as
 ≥1000 mg/m2 per day
 4-40 mg/m2/hr
• Def: urinary potein excretion above upper normal limit
in age <2yo < .5
in age >2yo < .2
 4-40 mg/m2/hr
Nephrotic range is defined as
 >40 mg/m2/hr
 Urine-pr/urin-creatine
Nephrotic range ≥3

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10% at age 8-15yrs
However, only 0.1 percent of children have persistent proteinuria
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The normally low rate is due to two factors:
1. Restriction of the filtration of proteins across the glomerular capillary wall
2. Reabsorption of freely filtered low molecular weight (LMW) proteins (less than 25,000
Daltons) by the proximal tubule
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Daltons) by the proximal tubule

Protective mechanisms against proteinuria:
1. Electrostatic barrier:
Negative charge in glomerular basement membrane glycosaminoglycan has a repelling action against
negatively charged circulating macromolecule (albumin)
2. Structural barrier:
blood renal barrier allows only passage of water and water-soluble substances.
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A. screening for proteinuria
1. Boiling test (urine clot by boiling)
2. Urine Dipstick
An excellent screening test
3. SULFOSALICYLIC ACID TEST
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Negative 0 Mg/Dl
Trace 15-30 Mg/Dl
1 + 30-100 Mg/Dl
2+ 100-300 Mg/Dl
3+ 300-1000 Mg/Dl
4+ >1000 Mg/Dl

False-positive tests
• urine specific gravity > 1.025,
• Alkaline urine
• Gross hematuria,
False negative test
• very dilute,
• Acidic urine (pH less than 4.5)
• Tubular protein
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• Gross hematuria,
• Pyuria & bacteriuria
• Urine contaminated with antiseptics
• such as chlorhexidine
• After radiographic contrast such as
• an intravenous urogram
• Tubular protein
• Microalbumin
• Globulins
• Bence-Jones
• protein in urine.

3. Quantitative assessment
A. Spot urine  protein to creatinine ratio (mg/mg)
1. < 0.2 :  Normal
2. 0.2 - 2 :  Nephriticrange
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2. 0.2 - 2 :  Nephriticrange
3. >2 :  Nephrotic range
B. 24 hrs urine protein
B. Qualitative assessment
urine protein electrophoresis (type of protein)

Urine protein Normal Non-Nephrotic range Nephrotic range
24-hr <150 mg/m
2
0.15-1 g/m
2
>1 g/m
2
mg/m
2
/hr <4 4-40 >40
Spot urine protein :creatinine <0.2 0.2-2.0 >2.0
Dipstick Negative/trace 1+/2+ 3+/4+
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Spot urine protein :creatinine <0.2 0.2-2.0 >2.0

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Causes of proteinuria
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Physiological:
Orthostatic
(postural)
Proteinuria
TRANSIENT
PROTEINURIA
Pathological:
Glomerular
Proteinuria
Tubular
Proteinuria
Overflow
proteinuria

Excessive protein filtration abnormally large amount of small (low MW)
protein present in the serum that exceeds the capacity of normal tubular
reabsorption (glomeruli are normal)
Causes:
1. Hemoglobinuria ,
2. Myoglobinuria
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2. Myoglobinuria
3. Multiple myeloma
4. Amyloidosis
5. Light chain disease
6. Hemoglobinuria
7. Myoglobinuria
8. Immunoglobulin light chains or Bence-Jones proteins
9. Dipstix negative

PROTEIN : CREATININE RATIO <1.0
Causes:
acute and chronic injuries involving the renal tubulointerstitial region
Mechanism:
Increased protein loss by injured tubules of small MW protein filtered by the glomeruli as
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Increased protein loss by injured tubules of small MW protein filtered by the glomeruli as
B2 microglobin or increased secretion of cellular enzyme by damaged tubules
Injury to the proximal tubules can result in diminished resorptive capacity and the loss of
these low molecular weight proteins in the urine
Asymptomatic patients having persistent proteinuria generally have glomerular
rather than tubular proteinuria

Excess urinary protein loss can result from increased permeability of the glomeruli to
the passage of serum proteins
Glomerular proteinuria can range from <1 g to >30 g/24 hr.
1. Selsctive :loss plasma protein up to and include albumin
2. Non-Selsctive: loss plasma albumin and larger as Ig
3. Microalbuminuria : 30-300 mg/ day
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3. Microalbuminuria : 30-300 mg/ day
Causes:
any glomerular disease
Mechanism:
1. loss of electrostatic charge of basement membrane,
2. damage of structural barrier caused by inflammation which affect size and selectivity of
pores,
3. Increase intraglomerular pressure due to hemodynamic changes

should be suspected in any patient with a first morning urine
protein : creatinine ratio >1.0, or proteinuria of any degree, accompanied by
1. Hypertension,
2. Hematuria,
3. Edema, Or
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3. Edema, Or
4. Renal Dysfunction

Nephrotic syndrome
is classically characterized by four clinical features, but the first two are used
diagnostically because the last two may not be seen in all patients:
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Nephrotic range
proteinuria
Hypoalbuminemia
Edema Hyperlipidemia

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Nephrotic range
proteinuria
Urine protein 3+ or 4+
urine protein to
creatinine ratio (Up/Uc)
>2 mg/mg in first
morning urine disease
proteinuria >40
mg/m2/hr

Incidence : 2-7:100,000 children/year
Prevalence : 12-16/100000 children
More in (Asians, Arab)

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Age group: 2-6 years
Male to female 2:1
Which is NOT a cause of nephrotic syndrome?
a) Lupus
b) Liver failure
c) Sarcoidosis
d) Minimal change diseas

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Etiology of NS
1. Primary (Idiopathic) NS (>90%)
I. Minimal change nephrotic syndrome (MCNS) (85%)
II. Focal segmental glomerulosclerosis (FSGS) (10-20%)
III. Membranoproliferative glomerulonephritis(MPGN) (5-15%)
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III. Membranoproliferative glomerulonephritis(MPGN) (5-15%)
IV. Membranous nephropathy (<5%)
2. Secondary NS (10%)(Systemic diseases that include kidney involvement)
3. Congenital NS

II. Secondary NS
• (Systemic diseases that include kidney
involvement)
• Infections
• Hepatitis B, C, HIV, EBV, CMV
• Malaria, syphilis
III. Congenital NS
• Presents during the first 2 months of life,
it may be:
• Primary congenital NS (Finnish type
congenital NS)
• Inherited as autosomal recessive
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• Malaria, syphilis
• Toxoplasmosis
• Immunologic or allergic disorders
• Systemic lupus erythematosus
• Henoch-Schonlein purpura
• Associated with malignant diseases
• Leukemia, Lymphoma
• Solid tumors
• Inherited as autosomal recessive
disorder
• Duo to defect in the nephrin gene that
codes for a protein in the GBM.
• Secondary congenital NS
• Infections: CMV, rubella

Histological
classification
Minimal change nephrotic syndrome (MCNS)
Focal segmental glomerulosclerosis (FSGS):
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Histological
classification
Mesangeal proliferative glomerulonephritis:
Membrano proliferative glomerulonephritis.
Membranous

Representing more than 90 percent of cases between 1 and 10 years
of age and 50 percent after 10 years of age
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Unknown cause
Respond to steroid therapy, remission 95%
Primary disorder of T- cell functioning

accurately differentiated children with MCD from those with other
glomerular pathology These findings included:
1. Age younger than six years of age
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1. Age younger than six years of age
2. Absence of hypertension
3. Absence of hematuria
4. Normal complement levels
5. Normal renal function

Primary glomerular disease with nephrotic syndrome
Most common in children, especially young children
It is the classic form of nephrotic syndrome, characterized by:
1. Absence of nephritic manifestations as hematuria, HTN, and renal failure.
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1. Absence of nephritic manifestations as hematuria, HTN, and renal failure.
2. Good response to steroid therapy.
Prevalence:
Age: peak incidence between 2-6 years.
Children 7-16 years old with NS have a -50% chance of having MCNS.
Sex: male: female ratio 2:1

secondary causes:
cancer, infection, drugs, atopy (hyperallergic)
Associated with lymphoma and use of NSAIDs
1. Light microscopy & immunoflorescence → normal.
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2. Electron microscopy → lost foot processes of podocytes.
3. Usually with selective proteinuria.
4. Steroid responsive in > 95%

Nephrotic Syndrome in 1st three months
1. Finnish type (most common form of congenital NS)
2. Diffuse mesangial sclerosis Eg. Denys Drash syndrome
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2. Diffuse mesangial sclerosis Eg. Denys Drash syndrome
3. Congenital infection Eg. TORCHS, HBV
Anasarca, Hypoalbuminemia, Oliguria

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↓protein
Massive Proteinuria Frothy urine
↓ immunoglobulins
Infection ↓ albumin <3 g/dL
↓ ATlll
Thrombosis
↑ liver activity
↓ plasma oncotic pressure
↓ ECV
Glomerular damage, Increased
permeability to proteins Proteinuria
Thrombosis
↑ liver activity
↓ plasma oncotic pressure
Edema Hyperlipidemia
↓ ECV
↓ GFR
↑ RAAS
↑ Na/H2O
Retention

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Specific Symptoms: Non-specific Symptoms:
1. Fatigue and lethargy
2. Loss of appetite
3. Nausea and vomiting
Massive
Proteinuria
Frothy urine
hypoalbuminemia
Edema (periorbital, face, in lower
extremities)
Age group: 2-5 years
Male to female 2:1
3. Nausea and vomiting
4. abdominal pain and
diarrhea
5. Body weight increase
6. Urine output decrease
7. Pleural effusion
(Respiratory distress)
8. Thrombosis
9. Infection
General edema (Anasarca)
Ascites
Rare
1. microscopic hematuria
2. hypertension

A. Clinically
1. Peripheral hypoperfusion (cold hands or feet, capillary refill time >2 sec).
2. Tachycardia,
3. Oliguria,
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3. Oliguria,
4. Hypotension {late sign).
B. Laboratory
1. Serum albumin level usually is less than 1.5 g/dl
2. Hemoconcentration (increased hemoglobin)

Atypical features at onset
1. Age <9-12 mo or >12-yr
2. Rash, arthralgia
3. Lack of edema
4. Significant hypertension
5. Persistent microscopic hematuria
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5. Persistent microscopic hematuria
6. Impaired renal function

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Infection
Due to
1. Loss of immunoglobulins in urine,
2. use immunosuppressive agents,
3. Malnutrition
4. Edema
Common infections:
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Common infections:
1. URI, Peritonitis,
2. Cellulitis,
3. meningitis,
4. UTI
Organisms:
bacteria
 Pneumococci, H.influenza, Gram negative organisms (E.coli),
viral
 Varicella:

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Acute renal failure (Nephrotic crisis)
Precipitated by
1. Severe hypovolemia →↓renal blood flow (pre renal failure).
2. Renal vein thrombosis.
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2. Renal vein thrombosis.
3. Sepsis

Cardiovascular disease
Hyperlipidemia may be a risk factor for cardiovascular disease.
Drugs complications:
Others
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Others
Growth retardation, cortical insufficiency

Thrombotic Complication
Hypercoagulability in NS:
1. Loss of anti-thrombin III→→decrease fibrinolysis
2. Higher concentration of I,II,V,VII,X factors and fibrinogen
3. higher blood viscosity
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3. higher blood viscosity
4. thrombosis (Renal, pulmonary, cerebral)
Precipitated by
1. Hypovolemia —> hemoconcetration—> sluggish circulation
2. Increased platelet adhesiveness and certain coagulation factors.
3. Decreased natural anti-coagulants e.g. Anti thormbin III and protein C.

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Steroids
1. Cataract
2. Ulcers (peptic) ĺadd ranitidine or proton pump inhibitor
3. Striae
4. Hypertension
5. Infections due to immunosuppression
6. Necrosis of bone ĺ may require calcium and vit D
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6. Necrosis of bone ĺ may require calcium and vit D
7. Growth retardation ĺmonitor height Q 3 months
8. Osteoporosis
9. Intracranial hypertension
10. Diabetes Mellitus
11. Myopathy (proximal)
12. Adipose tissue hypertrophy (moon face, Bufflo hump, trunkal obesity)
13. Pancreatitis

Cyclophosphamide
1. Alopecia
2. Bone marrow suppression
3. Hemorrhagic Cystitis (prevented by I.V. Mesna)
4. Decreased fertility
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Cyclosporin A
1. Hypertrichosis
2. Hypertension
3. Hyperplasia of gums
4. Nephrotoxicity

Mycophenolate mofetil
1. Leucopenia /anemia
2. GIT ulcerations
Tacrolimus
1. Hyperglycemia
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1. Hyperglycemia
2. Nephrotoxicity
Rituximab
1. Immunosuppression
2. Unclear long term safety profile

1. Overwhelming infections
2. Hypovolemic shock
3. Renal failure
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D.D of generalize edema (Anasarca)
1. Protein losing enteropathy
2. Hepatic failure
3. Heart failure
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3. Heart failure
4. Protein energy malnutrition
5. Acute and chronic glomerulonephritis
1+ Mild pitting
2+ Moderate pitting
3+ Deep pitting
4+ Very deep pitting

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How to confirm diagnosis of nephrotic syndrome
Urinalysis Blood tests Renal biopsy
ADDITIONAL EVALUATION
1. Proteinuria
2. Hyaline casts.
3. Microscopic hematuria in
25% of MCNS
1.Serum albumen: low
2.Serum cholesterol,
triglycerides: increased
3.Serum urea and creatinine:
normal or slightly increased
1. Tuberculin test (high endemicity for
tuberculosis)
2. C3 and antistreptolysin O (gross or
persistent microscopic hematuria)
3. Chest X-ray (positive tuberculin;
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normal or slightly increased
4.Serum C3, C4: normal (low
C3 means a lesion other than
MCNS)
3. Chest X-ray (positive tuberculin;
history of contact with tuberculosis)
4. Hepatitis B surface antigen (recent
jaundice, raised transaminases)
5. Antinuclear antibodies (if features of
systemic lupus erythematosus)
6. Urine culture (if clinical features of
urinary tract infection)

ABDOMINAL ULTRASOUND
CHEST X-RAY
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renal biopsy is not required for children presenting with
idiopathic nephrotic syndrome for the following reasons.
1. About 80% of children 1to 12 years of age with idiopathic have
minimal change nephrotic syndrome.
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minimal change nephrotic syndrome.
2. 93.1 - 97% of patients MCNS respond to corticosteroid therapy
3. 91.8% of steroid responders have minimal change disease.
 A renal biopsy is also NOT required prior to cytotoxic therapy

At onset
Age at onset <9 months or >16 yr
Gross hematuria
Later
Diagnosis of steroid resistance
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Persistent microscopic hematuria
Low serum C3
Renal failure, not attributable to hypovolemia
Suspected secondary causes (SLE, IgA)
Sustained severe hypertension.
Diagnosis of steroid resistance
Therapy with calcineurin inhibitors is
planned

1. steroid resistance (SRNS)
2. Congenital & Infantile forms
5. Presence of syndromic features
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4. Family history of SRNS or FSGS

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Reasons for admission
1. Hypovolemia;
2. severe anasarca
3. Infections: cellulitis; peritonitis
3. Infections: cellulitis; peritonitis
4. Thrombosis
5. First attack for education

Steroid – Sensitive Nephrotic Syndrome
1. MONITORING
2. STEROID THERAPY (SPECIFIC)
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2. STEROID THERAPY (SPECIFIC)
3. GENERAL THERAPY (NON- SPECIFIC) FOR COMPLICATIONS
Steroid – Resistant Nephrotic Syndrome
10% - 15 % of Nephrotic Syndrome

Follow up
1. Urine protein diary
2. Anthropometry
3. Steroid toxicity
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3. Steroid toxicity
4. Steroid resistance
Relapses
Blood creatinine, albumin, electrolytes
SRNS
Hepatitis B, C, and HIV

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In patients who fulfill all of the following clinical criteria:
1. Age older than 1 year and younger than 10 years of age (this is in general,
because in our practice we prescribe steroid for age > 10 year)
2. None of the following findings: hypertension, gross hematuria, marked
elevation in serum creatinine
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4. No extra renal symptoms, such as malar rash or purpura

1.5 mg/kg (Max 40 mg) on alternate day single morning dose X 6 weeks
Prednisolone: 2mg/kg/day(Max 60 mg) , divided into twice or three doses X 6 weeks
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If not responded till 8th week of prednisolone = Steroid resistant (SR)
Few patient respond after 4-6 weeks of prednisolone = Late responder
Most patient respond by end of 2nd week of prednisolone = Early responder

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40 mg/m² per alternate day or 1∙5 mg/kg/alternate day (max 40 mg) × 4 weeks
30 mg/m² per alternate day × 8 days (maximum 30 mg)
5 mg/m2/day per alternate day × 8 days
Then cease

Complete
remission:
Absence of
proteinuria (Up/Uc
ratio <0.2 g/g);
Partial remission:
Non nephrotic
proteinuria (Up/Uc
ratio of 0.2 to 2.0
Non remission:
Persistent nephrotic-
range proteinuria
(Up/Uc ratio >2 g/g),
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ratio <0.2 g/g);
serum albumin >2.5
g/dL; no edema
complete remission
90%
ratio of 0.2 to 2.0
g/g); scrum albumin
>2.5 g/dL; no edema
partial remission
80%
(Up/Uc ratio >2 g/g),
scrum albumin <2.5
g/dL or edema
non-remission 50%

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1. Up to 85% of children respond to corticosteroids
2. One third single episode
3. 40-50% frequent relapses or steroid dependence; often prolonged course
4. Long term issues
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4. Long term issues
1. Risk for relapses
2. Adverse effects of treatments
3. Renal function usually stable
5. Frequent relapsing nephrotic syndrome of childhood can persist after
puberty in >20% of patients
6. 10-15% of children are refractory to corticosteroids

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Nephrotic range
proteinuria
1. Urine protein 3+ or 4+;
2. urine protein to creatinine ratio (Up/Uc) >2 mg/mg in first
morning urine disease;
3. proteinuria >40 mg/m2/hr
Remission Urine protein nil or trace (Up/Uc <0.2 mg/mg) for 3 consecutive
early morning specimens
Relapse Urine protein >3+
Relapse Urine protein >3+
(Up/Uc >2 mg/mg) for 3 consecutive early morning specimens,
having been in remission previously
Frequent relapses • Two or more relapses in the first 6-months after stopping
initial therapy
≥ 3 relapses in any 6-months; or
≥ 4 relapses in one yr

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Steroid
dependence
• Two consecutive relapses when on alternate day steroids, or within
14 days of its discontinuation
Steroid
resistance
• Lack of complete remission despite therapy with daily
prednisolone at a dose of 2 mg/kg (or 60 mg/m2) daily for 6 weeks
1. Initial resistance-Non response to initial steroid therapy
2. Late resistance- failure to respond in subsequent relapses after
initial response to steroids
initial response to steroids
Complicated
relapse
Relapse associated with life-threatening complications:
1. hypovolemia requiring inpatient care,
2. severe infection (peritonitis,cellulitis, meningitis), or (iii)
thrombosis

1. Onset < 4-yr
2. Initial therapy < 8- wk
3. Initial remission < 6-mo
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4. Boys
5. Prolonged time to first remission
6. Infection, hematuria with first episode

Alternate-day prednisolone
1. Levamisole
2. Cyclophosphamide
3. Mycophenolate mofetil
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3. Mycophenolate mofetil
4. Tacrolimus, Cyclosporin
5. Rituximab

Definition:
Lack of complete remission despite therapy with daily prednisolone at a dose
of 2 mg/kg (or 60 mg/m2) daily for 6 weeks (update)
Late steroid resistance Remission after initial therapy , but failure to respond
during a subsequent relapse
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during a subsequent relapse
Evaluation
Diagnostic kidney biopsy
Estimated GFR
Measure, urine protein excretion
Routine evaluation for genetic mutations: not recommended

Cyclosporine + Prednisolone + Enalapril
Cyclosporine 4-5mg/kg/day
12 – 36 months +
Prednisolone tapering doses
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Prednisolone tapering doses
18 months +
Enalapril
0.3 – 0.6 mg/kg/day (is associated with decrease in proteinuria, control
hypertension)

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Bed rest
This is not required and usually not practical unless the child has gross
oedema.
Diet
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Diet
A normal protein diet with adequate calories is recommended. Previous
recommendations of high protein diet had not been shown to improve
serum albumin concentration.
Salt intake should be reduced during the oedematous state.

Precipitated by
1. Sepsis
2. Diarrhea
3. Use of diuretics
Clinical features
 Abdominal pain, vomiting, lethargy
 Prolonged capillary refill time; cold extremities
 Tachycardia, low volume pulses
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 Tachycardia, low volume pulses
 Low blood pressure; postural hypotension
Biochemical indices
 Elevated hematocrit
 Fractional excretion of sodium <0.5%
 Elevated ratio of urea to creatinine,
Management
 Discontinue diuretics
 Hypotensive : isotonic saline bolus and/or 5% albumin
 Oral / iv hydration/ albumin infusion

Category Mild Moderate Severe
% of wt gain <7% 8-15% >15%
Management Salt Diuretics Diuretics
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Management
of edema
Salt
restriction
Diuretics Diuretics

Assess
for
hypovolemia
No
Mild edema Salt restriction
Moderate to severe edema Diuretics
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Assess
for
hypovolemia
Yes
Hypovolemic shock: NS or 5% albumin bolus
No evidence of shock: ensure urine output then IV albumin 0.5-1
g/kg ± furosemide 0.5-1 mg/kg

Risk of worsening hypertension, respiratory distress and heart failure
Ensure urine output before infusion
Slow infusion followed by diuretics preferred
The use of intravenous albumin is indicated in cases with:
Symptomatic hypovolemia
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Symptomatic hypovolemia
10 – 20 ml /kg of 4.5 – 5% albumin should be infused.
Symptomatic edema + Marked ascites (respiratory compromise)
0.75 – 1 g/kg of 20% albumin, infused over 2 hours
In order to expand the circulating volume followed by furosemide 1mg/kg.
Close monitoring to avoid overload/pulmonary edema

Agent Time period
NO
contraindication for
vaccination
Live vaccine <5 days
Contraindication for Varicella immunoglobulin 125 <10 days preferably less
More than 5 minutes of face-to-face contact with individual with varicella or zoster, while
indoors
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Contraindication for
vaccination
Varicella immunoglobulin 125
IU/10 Kg body wt, max 625 IU im
<10 days preferably less
than 4 days
Acyclovir 80 mg/Kg, 4 divided
doses *7d
6-10 days after exposure
Valacyclovir 60 mg/Kg, 3 divided
dose * 7d
IVIG 400 mg pe Kg <10 days

Acute Adrenal Crisis
 This may be seen in children who have been on long term corticosteroid
therapy (equivalent to 18 mg/m2 of cortisone daily) when they undergo
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therapy (equivalent to 18 mg/m2 of cortisone daily) when they undergo
situations of stress.
Adequate cover with corticosteroids during these periods of stress is
recommended to be given in 3 divided doses.
Hydrocort 100mg/m2 followed by 25 mg/m2

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Up to 85% of children respond to corticosteroids
MCNS
30% : Single relapse
20%: infrequent relapsing
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20%: infrequent relapsing
50 — 60%: frequent relapsing
Steroid resistant NS :
poor ,
progressive renal insufficiency

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Dr. Reyad Ahmed Abdu Mansoor
consultant pediatrician in university of Science & Technology Hospital ,
consultant pediatrician . in Al-sabeen Hospital
Associated Member Of The Arabic Board

Types of proteinuria
Symptoms
Symptomatic Asymptomatic
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Symptomatic
Refer to nephrologist
Asymptomatic
Transient persistent
Orthostatic(Postural) Fixed

is the most common cause
In 10% of children who undergo random urinalysis
usually does not exceed 1-2+ on the dipstick
1. Dehydration
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1. Dehydration
2. Emotional stress
3. Fever
4. Heat injury
5. Intense physical activity
6. Most acute illnesses
7. Orthostatic (postural )disorder
8. PREGNANCY

defined as increased protein excretion in the upright position which returns to
normal when the patient is recumbent
is the most common cause of persistent proteinuria in school-aged children and
adolescents
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occurring in up to 60% of children with persistent proteinuria
diagnosis of orthostatic proteinuria
a condition in which the 24-hr urinary protein excretion rarely exceeds 1 g
The absence of proteinuria (dipstick negative or trace for protein and urine Pr : Cr ratio <0.2) in the
first morning urine sample for 3 consecutive days

Fixed proteinuria is defined as
a first morning urine sample that is ≥1+ on dipstick testing with a urine specific gravity >
1.015 or with a urine protein-to-creatinine ratio of ≥ 0.2.
Fixed proteinuria indicates a potential kidney disease caused by either
glomerular or tubular disorders.
Glomerular Proteinuria
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Glomerular Proteinuria
The glomerular capillary wall consists of three layers: the fenestrated capillary
endothelium, the glomerular basement membrane, and the podocytes (with foot processes
and intercalated slit diaphragms)
Glomerular proteinuria results from alterations in the permeability of any of the layers of
the glomerular capillary wall to normally filtered proteins and occurs in a variety of renal
diseases.

How to approach a child with proteinuria???
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History and physical examination
Asymptomatic Symptomatic

History
• The duration of proteinuria
• Symptoms of NS
• Symptoms of collagen
physical examination
• Blood pressure
• Test for edema
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• Symptoms of collagen
vascular disease
• [fever, rash, joint pain)
• Drug history
• Family history of any renal
disease

Child with asymptomatic proteinuria
Abnormal urine dipstick analysis >1+
Repeat urine analysis, one week apart
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Repeat urine analysis, one week apart
Negative
Transient proteinuria
No further workup
Still positive
Persistent proteinuria
Orthostatic proteinuria Fixed proteinuria

Single urine positive for protein
Obtain:1) first morning void Pr/Cr 2) UA in office
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Pr/Cr and UA normal
Transient Proteinuria
Pr/Cr normal, UA positive
Orthostatic Proteinuria
Both specimens abnormal
Persistent Proteinuria

should have periodic re-evaluation
every 4-6 mos unless the patient is symptomatic
consisting of
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consisting of
1. physical examination
2. blood pressure determination
3. Urinalysis
4. measurement of serum creatinine
5. first morning voided urine protein / creatinine ratio

Abnormal urine dipstick analysis + edema
Obtain urine? sample for Upr/Ucr ratio
Serum albumen
Serum cholesterol and TG
Serum urea and creatinine
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Serum urea and creatinine
Serum electrolytes
Serum complement (C3)
Nephrotic range proteinuria + hypoalbuminemia+ hyperlipidemia +edema
Confirm diagnosis of nephrotic syndrome

• In patients who fulfill all of the following clinical
criteria:
1. Age older than 1 year and younger than 10
years of age (this is in general, because in
our practice we prescribe steroid for age >
10 year)
2. None of the following findings:
hypertension, gross hematuria, marked
4. No extra renal symptoms, such as malar
• Features of non minimal change NS
1. Age: >10 years
2. Presence of nephritic manifestations
(hematuria,. HTN, renal impairment,
lowC3)
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4. No extra renal symptoms, such as malar
rash or purpura
IF no response to treatment after 2
ms
Renal biopsy should be done
before starting treatment

1. Perform Orthostatic Test
2. CBC
3. BUN
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4. Creatinine
5. Electrolytes
6. 24-hr urine excretion
< 1.5g/day  repeat UA and blood work in 1 year
> 1.5g/day  refer to Pediatric Nephrologist

1. Renal ultrasound
2. Serum complement levels (C3 and C4)
3. ANA
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4. Streptozyme testing,
5. Hepatitis B and C serology
6. HIV testing

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A. Specific treatment; Successful treatment of the cause will remain the corner
stone of therapy.
B. Non-Specific treatment:
1. Dietary protein intake. (+) to O.6gm/day+ urine loss.
2. ACE inhibitors: It should be avoided of the serum creatinine is above 2.7mg/dl or
increasing by its use.
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increasing by its use.
3. ARBs: may be superior to ACE inhibitors.

LECTURE NEPHROTIC SYNDROME.pdf

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LECTURE NEPHROTIC SYNDROME.pdf