Nephrotic Syndrome
Dr. Yasmin
Objectives
Determine transient vs.
pathologic proteinuria
Recognize the presentation of
nephrotic syndrome
Distinguish between idiopathic
and secondary forms of nephrotic
syndrome
Identify possible complications of
nephrotic syndrome
PROTEINURIA
Proteinuria
Transient
◦ Fever
◦ Exercise
◦ Convulsions
Orthostatic
◦ Noted when child is upright
◦ Check early morning urines
Glomerular
◦ Nephrotic
◦ Glomerulonephritis
NEPHROTIC
SYNDROME
Nephrotic Syndrome
Increasedpermeability of the
glomerulus causing
◦ Proteinuria
◦ Edema
◦ Hypoalbuminemia < 2.5 gm/dL
◦ Hyperlipidemia
Glomerular Anatomy
Proteinuria
Defined as
> 40 mg/m2/hr
4+ on urine dipstick
◦ Spot urine protein:creatinine ratio >
0.2
Pathophysiology of Edema
Liver Hyperactivity
Hypoalbuminemia stimulates
liver protein synthesis causing
◦ Hyperlipidemia
◦ Hypercoagulable state from increase
production of clotting factors and
loss of antithrombins in urine
Infection Risk
Immunoglobulins and
complement also lost through
urine
Greater risk for infections with
encapsulated organisms
◦ H. influenza
◦ Strep pneumo
◦ N. meningitidis
Causes
Idiopathic
◦ Minimal Change Disease
◦ Focal Segmental Glomerulosclerosis
◦ Membranous Nephropathy
Secondary to infection
Drug induced (NSAIDs)
Sickle cell disease
Secondary to malignancy
(leukemia, lymphoma)
Infectious Causes of
Nephrotic Syndrome
GN Infection
Membranous Malaria (P. malariae)
Hepatitis B
Schistosoma
Leprosy
Loa Loa
Syphiis
FSGS HIV
Schistosoma
Proliferative GN Strep
Staph
Schistosoma
Leprosy
Wuchereria bancrofti
Onchocerciasis
Primary glomerular disease without a systemic
cause
IDIOPATHIC
NEPHROTIC
SYNDROME
Minimal Change Nephrotic
Syndrome (MCNS)
Most common cause of idiopathic
nephrotic syndrome
Boys > girls
Peak age 2-6 years
Symptoms usually follow minor
infections
◦ May confuse with PSGN
Normal glomeruli on biopsy
95% of children will respond to
steroid therapy
Clinical Symptoms
Periorbitaland lower extremity
edema initially
◦ Dependent edmea
Generalized edema
◦ Edema of the intestinal wall loose
stools (diarrhea)
Ascites
Pleural effusions
Clinical Symptoms
Anorexia
Irritability
Abdominal pain
Absence of hypertension and
gross hematuria
◦ BP usually normal or low
Periorbital
Edema
At what time of day is periorbital edema most
prominent?
Periorbital
Edema
Where does the edema move throughout the
day?
Pedal Edema
Testicular Edema
Ascites
PLEURAL EFFUSIONS
Notice the layering
Differential Diagnosis
Hepatic failure
Heart failure
Acute or chronic
glomerulonephritis
◦ FSGS
Protein malnutrition
Diagnosis
Urinalysis
◦ 3-4+ proteinuria
◦ Microscopic hematuria present in 20%
24-hour
protein collection >
40mg/m2/hr
◦ Normal < 4 mg/m2/hr
◦ Proteinuria 4-40 mg/m2/hr
◦ Nephrotic > 40 mg/m2/hr
Spot urine protein:creatinine ratio
> 0.2
Diagnosis
Creatinine usually normal
◦ May be elevated if severely reduced
plasma volume (prerenal)
Electrolytes (hyponatremia)
Albumin < 2.5 g/dL
Elevated serum
cholesterol/triglycerides
Elevated Hb (hemoconcentration)
Evaluation for causative infections
◦ Malaria, hepatitis, HIV
Renal Biopsy?
Renal biopsy not indicated
symptoms consistent with MCNS
Consider biopsy if
◦ Gross hematuria
◦ Hypertension
◦ Renal insufficiency
◦ Hypocomplementemia
◦ Age <1 yr or >8 yr
◦ Poor response to steroid treatment
Treatment
Priorto starting treatment, screen for
symptoms of TB infection
Treatment
◦ Prednisone 60 mg/m2/day (maximum daily
dose, 80 mg) as a single daily dose for 4-6
consecutive wk
>80% of patients respond within 3 weeks
◦ Prednisone 40 mg/m2/day given every
other day as a single daily dose for at
least 4 wk
◦ Taper off prednisone over next 1-2 months
When to Hospitalize?
Severe symptomatic edema
◦ Large pleural effusions
◦ Ascites
◦ Severe genital edema
Respiratory distress
Signs of infection
◦ Spontaneous bacterial peritonitis
with ascites
Hospital Management
Sodium and fluid restriction
Diuresis with caution
◦ Diuresis decreases plasma volume
and can precipitate thrombosis
Initiate
steroid treatment
Monitor for complications
◦ Pleural effusions
◦ Ascites
◦ Infection
Relapse
Relapse rates: 30-40%
Relapse Treatment
◦ Prednisone 60 mg/m2/day (80 mg
daily max) in a single am dose until
the child enters remission (urine
trace or negative for protein for 3
consecutive days).
◦ Then changed to alternate-day
dosing as noted with initial therapy,
and gradually tapered over 4-8 wk.
Relapse
Steroid dependent
◦ Relapse while on alternate-day
dosing or within 28 days of
completing therapy
Frequent relapsers
◦ Respond well to steroids but >4
relapses within one year
Steroid resistant
◦ No response within 8 weeks of
steroid therapy
◦ Often caused by FSGS
Alternatives During
Relapse
To avoid chronic side effects of
steroids
Cyclophosphamide
◦ 2 mg/kg) is as a single oral dose for
a total duration of 8-12 wk
◦ Continue alternate-day steroids
during course
Complications: Infection
Complications:
Thrombosis
Arterialor venous thrombosis
Prevention
◦ Avoid aggressive use of diuretics
◦ Avoid indwelling central catheters
RENAL VENOUS
THROMBOSIS
Lack of venous Doppler pulsations on
left
Prognosis
Repeated relapses
◦ Decrease in frequency with age
Ifno relapses in the first 6 months
after treatment, likely infrequently
relapser
Steroid resistant – poorer
prognosis
◦ FSGS likely
◦ Progression to renal failure, dialysis,
transplant
Focal Segmental
Glomerulosclerosis (FSGS)
Lesions that are both focal (present
only in a proportion of glomeruli)
and segmental (localized to ≥1
intraglomerular tufts)
Biopsy positive for IgM and C3 on
immunofluorescence
Only 20% respond to steroid therapy
Progressive, usually leads to renal
failure
Infectious Nephroses
Most common infectious causes
of nephrotic syndrome in
developing countries
◦ Malaria
◦ Schistosoma
Can cause differing types of
nephrotic disease
◦ Membranous
◦ FSGS
◦ Membranoproliferative
Primary Renal Diseases
Causing Nephrotic Syndrome
CASE EXAMPLES
A 4-year-old previously healthy boy
presents with 1 day of scrotal swelling.
His mother noted his scrotum to be
markedly swollen and thinks his eyes
are puffy. Examination reveals an
afebrile child with a BP of 90/50 mm Hg.
He is alert with significant bilateral
periorbital edema. His abdomen has
ascites with no organomegaly. His
scrotum and lower extremities have
tense pitting edema.
The initial laboratory test most
likely to point to the etiology of
his illness is as which of the
following?
(A) chest radiograph
(B) liver biopsy
(C) urine analysis
(D) hepatitis panel
(E) stool guaiac and pH
The initial laboratory test most
likely to point to the etiology of
his illness is as which of the
following?
(A) chest radiograph
(B) liver biopsy
(C) urine analysis
(D) hepatitis panel
(E) stool guaiac and pH
Subsequent testing reveals a serum
albumin of 1 g/dL, a cholesterol level of
560 mg/dL (nL109–189 mg/dL), and
normal complement and liver enzyme
levels. The most likely diagnosis for this
patient is which of the following?
(A) membranous glomerulonephritis
(B) focal segmental glomerulosclerosis
(C) poststreptococcal glomerulonephritis
(D) membranoproliferative
glomerulonephritis
(E) minimal-change disease
Subsequent testing reveals a serum
albumin of 1 g/dL, a cholesterol level of
560 mg/dL (nL109–189 mg/dL), and
normal complement and liver enzyme
levels. The most likely diagnosis for this
patient is which of the following?
(A) membranous glomerulonephritis
(B) focal segmental glomerulosclerosis
(C) poststreptococcal glomerulonephritis
(D) membranoproliferative
glomerulonephritis
(E) minimal-change disease
Which of the following statements regarding
this patient’s most likely condition is true?
(A) It almost never responds to steroid
therapy.
(B) Spontaneous bacterial peritonitis is not
a concern.
(C) These patients have an increased
tendency to hemorrhage.
(D) A low-salt diet is essential during flares
of the illness.
(E) Nonresponse to therapy for at least 1
year should prompt a nephrology referral
for biopsy.
Which of the following statements regarding
this patient’s most likely condition is true?
(A) It almost never responds to steroid
therapy.
(B) Spontaneous bacterial peritonitis is not
a concern.
(C) These patients have an increased
tendency to hemorrhage.
(D) A low-salt diet is essential during flares
of the illness.
(E) Nonresponse to therapy for at least 1
year should prompt a nephrology referral
for biopsy.
Summary
Nephrotic syndrome is defined by
proteinuria, edema, low albumin,
elevated cholesterol
Most common causes are MCNS
and secondary to infection
(malaria and schistosoma)
Treatment is empiric; renal
biopsy only needed if poor
response to treatment
A 5-year-old boy presents with fever, cough,
and body aches. Physical examination reveals a
temperature of 38.6°C, heart rate of 86
beats/minute, respiratory rate of 20
breaths/minute, and blood pressure of 106/60
mm Hg. He has rhinorrhea and tonsillar
erythema. Urinalysis demonstrates a specific
gravity of 1.020, pH of 6, 2+ protein, and no
blood. Of the following, the MOST likely cause
for this patient's urinary findings is
A. Alport nephritis
B. false-positive effect of urine pH
C. fever
D. minimal change disease
E. poststreptococcal glomerulonephritis
A 5-year-old boy presents with fever, cough,
and body aches. Physical examination reveals a
temperature of 38.6°C, heart rate of 86
beats/minute, respiratory rate of 20
breaths/minute, and blood pressure of 106/60
mm Hg. He has rhinorrhea and tonsillar
erythema. Urinalysis demonstrates a specific
gravity of 1.020, pH of 6, 2+ protein, and no
blood. Of the following, the MOST likely cause
for this patient's urinary findings is
A. Alport nephritis
B. false-positive effect of urine pH
C. fever
D. minimal change disease
E. poststreptococcal glomerulonephritis
QUESTIONS?
