Management Of Nephrotic Syndrome
Objectives
To briefly review the definition & etiology of nephroticsyndrome.
To understand the terminology pertaining to clinical course of nephroticsyndrome.
To understand the management of nephroticsyndrome:Specific management & Supportive care and management of complications
Management of congenital nephrotic syndrome
2. Objectives
• To briefly review the definition & etiology of nephrotic
syndrome.
• To understand the terminology pertaining to clinical
course of nephrotic syndrome.
• To understand the management of nephrotic
syndrome:
Specific management
Supportive care and management of complications
Management of congenital nephrotic syndrome
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
3. Definition
Nephrotic syndrome, is a manifestation of glomerular
disease (due to various etiologies) characterized by,
Nephrotic range
proteinuria
• Early morning urine protein is 3+/4+
(on dipstick or boiling test) or
• Spot protein/creatinine ratio >2
mg/mg, or
• Urine albumin excretion >40 mg/m2
per hr (on a timed-sample) or
• Urine protein excretion > 50 mg/kg/24
hr
Hypoalbuminemia • Serum albumin < 2.5 g/dL
Hyperlipidemia • Serum cholesterol >200 mg/dL
Generalised Edema
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
4. Etiology of nephrotic syndrome
In 95% cases there is primary
glomerular abnormality.Remaining
are secondary to systemic disorder.
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
6. Evaluation at onset
• Essential investigations:
Urinalysis: Proteinuria, red cells, casts; Spot urine protein creatinine ratio
Blood levels of urea, creatinine, albumin, cholesterol
Complete blood count
Tuberculin test
• If required:
C3 and ASO titres (gross or persistent microscopic hematuria)
Chest X-ray (positive tuberculin test, history ofTB contact)
HIV, HBV, HCV serology in highrisk groups
ANA (if features of SLE are present)
Urine culture (if clinical features of UTI are present)
USG abdomen (to ruleout anomalies in kidney)
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
7. Indications for renal biopsy
• At Onset (If cause other than minimal change nephrotic
syndrome is suspected)
• Age of onset <1 year.
• Gross hematuria, persistent microscopic hematuria or low serum
C3.
• Sustained hypertension.
• Renal failure not attributable to hypovolemia.
• Suspected secondary causes of nephrotic syndrome.
• After InitialTreatment
• Proteinuria persisting despite 4-weeks of daily corticosteroid
therapy – steroid resistance.
• Before treatment with Cyclosporin A orTacrolimus.
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
8. Management of the initial episode
• Appropriate therapy at the first episode is an
important determinant of the long term course of the
disease.
• Prednisolone is the drug of choice.
• It is given at a dose of 2 mg/kg per day (maximum 60
mg in single or divided doses) for 6 weeks, followed by
1.5 mg/kg (maximum 40 mg) as a single morning dose
on alternate days for the next 6 weeks; therapy is then
discontinued.
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
9. Following initial treatment with steroids for 12 weeks,
the disease may take any of the following course:
Remission
Urine albumin nil or trace (or proteinuria <4
mg/m2/hr) for 3 consecutive early morning
specimens.
Relapse
Urine albumin 3+ or 4+ (or proteinuria >40
mg/m2/hr) for 3 consecutive early morning
specimens, having been in remission previously.
Frequent
relapses
Two or more relapses in initial six months or more
than three relapses in any twelve months.
Infrequent
relapses
Three or less relapses a year.
Steroid
dependence
Two consecutive relapses when on alternate day
steroids or within 14 days of its discontinuation.
Steroid
resistance
Failure to achieve remission despite therapy with
daily prednisolone at a dose of 2 mg/kg per day for
4 weeks. Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
10. Treatment of relapse
• Relapse is defined as urine albumin 3+ or 4+ (or proteinuria
>40 mg/m2/hr) for 3 consecutive early morning specimens,
having been in remission previously.
• An URTI or some other infection usually precipitates a
relapse.
• Appropriate therapy of an infection before starting therapy
might result in spontaneous remission.
• Prednisolone is administered at a dose of 2 mg/kg/day
(single or divided doses) until urine protein is trace or nil
for three consecutive days.
• Subsequently, Prednisolone is given in a single morning
dose of 1.5 mg/kg on alternate days for 4 weeks, and then
discontinued.
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
11. Infrequent Relapsers
• An infrequent relapser is defined as initial responder
with three or less relapses a year.
• They are managed using standard prednisolone
regimen for each relapse.
• Such children are at a low risk for developing steroid
toxicity.
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
12. Management of Frequent Relapsers and
Steroid Dependence
• Frequent relapse is defined asTwo or more relapses in
initial six months or more than three relapses in any twelve
months.
• Steroid dependence is defined as occurrence two
consecutive relapses when on alternate day steroids or
within 14 days of its discontinuation.
• Following treatment of a relapse, prednisolone is gradually
tapered to maintain the patient in remission on alternate
day dose of 0.5-0.7 mg/kg.
• A close monitoring of growth and blood pressure, and
evaluation for features of steroid toxicity (cushingoid
features – obesity, hirsutism, striae, hypertension, impaired
glucose tolerance, posterior subcapsular opacities,
emotional problems & growth retardation) is essential.
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
13. Management of Frequent Relapsers and
Steroid Dependence contd.
• If prednisolone threshold to maintain remission less than
0.5-0.7mg/kg on alternate day and there is no steroid
toxicity, it is continued for 9-18 months.And then
breakthrough relapses are treated with standard therapy of
relapse.
• If prednisolone threshold to maintain remission greater
than 0.5-0.7mg/kg on alternate day and there is steroid
toxicity, addition of following immunomodulators is
suggested.
• Levamisole
• Cyclophosphamide
• Calcineurin inhibitors: Cyclosporin (CsA),
Tacrolimus
• Mycophenolate mofetil (MMF) Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
14. Levamisole
• Immunostimulant drug.
• Dose & duration: 2-2.5 mg/kg on alternate days for 12-
24 months
• Concomitant steroid therapy: Prednisolone dose is
gradually tapered to 0.25-0.5 mg/kg over a period of 8
months. Occasionally, it might be possible to
discontinue Prednisolone.
• Side effects: Neutropenia, flu-like symptoms, liver
toxicity, convulsions and skin rash.
• Monitoring:The leukocyte count should be monitored
every 3-4 months.
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
15. Cyclophosphamide
• Immunosuppressive drug.
• Dose & duration: 2-2.5 mg/kg/day for 12 weeks. Should
be started following remission of proteinuria.
• Concomitant steroid therapy: Prednisolone dose is
gradually tapered to 1 mg/kg over a period of 6
months and then stopped.
• Side effects: Hemorrhagic cystitis, alopecia, nausea
and vomiting, gonadal toxicity.
• Monitoring:Total leukocyte counts are monitored
every 2 weeks;temporarily discontinued if the count
falls below 4000/mm3.
• Use of more than one course (12 weeks) should
preferably be avoided in view of gonadal toxicity.Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
16. Calcineurin inhibitor : Cyclosporin (CsA)
• Immunosuppressive agent.
• Dose & duration: 4-5 mg/kg daily for 12-24 months.
• Concomitant steroid therapy: Prednisolone is gradually tapered
to 0.25-0.5 mg/kg over 8 or more months. Occassionally it can
be discontinued.
• Side effects: Hypertension, gum hypertrophy, hirsutism,
nephrotoxicity, hypercholesterolemia and elevated
transaminases.
• Monitoring: Plasma CsA levels should be kept between 80-120
ng/mL.
• Serum creatinine is monitored every 2-3 months.
• Lipid profile is checked annually.
• A repeat kidney biopsy, to examine for histological evidence of
nephrotoxicity, should be done if duration of treatment is
extended beyond 2 years.
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
17. Calcineurin inhibitor :Tacrolimus
• Immunosuppressive agent.
• Dose & duration: 0.1-0.2 mg/kg daily for 12-24 months.
• Concomitant steroid therapy: Prednisolone is gradually
tapered to 0.25-0.5 mg/kg over 8 or more months.
Occassionally it can be discontinued.
• Side effects: Hyperglycemia, diarrhea and rarely
neurotoxicity (headache, seizures).
• Preferred especially in adolescents, because of lack of
cosmetic side effects (Gum hypertrophy & hirsutism).
• Monitoring: Serum creatinine and glucose every 2-3
months.
• A repeat kidney biopsy, to examine for histological
evidence of nephrotoxicity, should be done if duration of
treatment is extended beyond 2 years.
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
18. Mycophenolate mofetil (MMF)
• Immunosuppressive agent.
• Dose & duration: 800-1200 mg/m2/day for 12-24
months.
• Concomitant steroid therapy: Prednisolone is
gradually tapered over 12-24 months. Recent trials
supported its use as a steroid sparing agent.
• Side effects: Gastrointestinal discomfort, diarrhea
and leukopenia.
• Monitoring: Leukocyte counts every 1-2 months;
Withheld if count falls below 4000/mm3
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
19. Choice of immunomodulator:
• First choice is Levamisole or
Cyclophosphamide.
• Cycloposphamide is preferred in patients
showing poor compliance or difficult follow-
up, where 12 weeks therapy is beneficial.
• Relapses occurring during immunomodulator
therapy must be treated with regular
Prednisolone relapse regimen.
• If there are two or more relapses over 6
months while on treatment with any of them,
its replacement with an alternative
medication should be considered.
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
20. Management of patients with steroid sensitive nephrotic syndrome
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
21. Steroid resistant nephrotic syndrome
• Failure to achieve remission despite therapy with
daily prednisolone at a dose of 2 mg/kg per day for 4
weeks is called steroid resistance.
• Incidence approximately 10-20%.
• Initial resistance: Lack of remission at the first
episode.
• Late resistance: Steroid sensitive initially, but show
steroid resistance during subsequent relapse.
• All chidren with steroid resistant nephrotic
syndrome should under go renal biopsy.
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
22. SRNS - renal biopsy rationale
• Most patients with steroid sensitive nephrotic syndrome
(90%) show minimal change nephrotic syndrome on renal
histology.
• 30-40% of SRNS patients show minimal change nephrotic
syndrome,30-40% show FSGS.
• 20% patients with SRNS show membranoproliferative
glomerulonephritis, membranous nephropathy, IgA
nephropathy and amyloidosis.These conditions differ in
their evaluation and treatment.
• The response to therapy is determined by renal histology;
patients with minimal change nephrotic syndrome show
satisfactory response to therapy, while presence of FSGS
or chronic tubulointerstitial changes is associated with
unsatisfactory outcomes.
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
23. Treatment regimens for SRNS
There is lack of consensus regarding the most
appropriate regimen, the choice of initial treatment
depends on the preference of the physician. Duration of
therapy is for 2-3 years. Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
24. SRNS - Management
• All patients with SRNS should receive treatment
with angiotensin converting enzyme inhibitors (e.g.,
Enalapril, Ramipril).
• These agents should be avoided if the estimated GFR
is <30 ml/minute/1.73 m2.
• Angiotensin receptor blockers (e.g.,
Losartan,Valsartan) may be used in patients
intolerant to ACE inhibitors, or as add-on therapy to
achieve better antihypertensive and antiproteinuric
effect.
• Dyslipidemia should be managed by HMG CoA
reductase inhibitors (e.g.Atrovastatin 10-20 mg
daily).Target LDL level is <130 mg/dL.
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
26. Dietary management
• A balanced diet, adequate in protein (1.5-2 g/kg) and
calories is recommended.
• Patients with persistent proteinuria should receive 2-
2.5 g/kg of protein daily.
• Not more than 30% calories should be derived from
fat.
• Treatment with corticosteroids stimulates appetite, so
adequate physical activity is to be ensured to prevent
excessive weight gain.
• Patients on prolonged (>3 months) treatment with
steroids should receive daily supplements of oral
calcium (250-500 mg/day) and vitamin D (125-250
IU/day).
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
27. Dietary management contd.
• Salt restriction is not necessary in most patients with
steroid sensitive nephrotic syndrome
• Reduction of salt intake (1-2 g per day) is advised for
those with persistent edema. Salt should not be added
to salads and fruits, and snacks containing high salt
avoided.
• Fluid restriction is needed in addition to Sodium
restriction in children with persistent edema.
• Severe edema: Intake of fluid restricted to insensible
water loss
• Moderate edema: Fluid intake = Insensible water loss
(400 mL/m2/day) + Previous day's urine output
• Mild edema: Fluid is minimally restricted Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
28. Edema – Underfill hypothesis
Heavy proteinuria
Hypoalbuminemia
Decreased plasma oncotic pressure
Transudation of fluid from intravascular to interstitial space
Decreased circulating blood volume (Underfill)
Activation of Renin-Angiotensin System
Elevated Aldosterone, ElevatedVasopressin
Sodium and water retention
Edema
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
29. Edema – Overfill hypothesis
Heavy proteinuria
Proteolytic enzymes enter
tubular lumen
Activation of Epithelial
Sodium Channels (ENaC)
Increased blood volume
(Overfill)
Edema
Hypoalbuminemia
Low plasma oncotic pressure
Intrinsic
resistance of
kidney to
ANP (Atrial
Natriuretic
Peptide)
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
30. • Prednisolone therapy usually results
in diuresis with in 5-10 days.
• Diuretics shouldn’t be given to
patients with diarrhea, vomiting or
hypovolemia. .
• Gradual reduction of edema over one
week is preferred.
• Spironolactone added for patients
requiring Furosemide dose
>3mg/kg/day or used >1 week.
• Monitor weight, urine output, BP,
heart rate & serum electrolytes of
patients who are on IV diuretic
therapy.
• In case of refractory ascites
interfering with respiration,
paracentesis should be done.Patients receiving Albumin should be observed for
respiratory distress (pulmonary edema), hypertension and
congestive heart failure.
Edema – Management
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
31. Hypovolemia
• May occur during severe disease relapse, following diuretic
administration particularly in children with poor oral
intake, diarrhea and vomiting.
• Symptoms: Dizziness, lethargy, abdominal pain and leg
cramps.
• Signs: Dry mucous membrane, orthostatic
hypotension,raised hematocrit, elevated blood urea, uric
acid, tachycardia, feeble pulses, cold extremities, slow
capillary refill, low FENa & high urinary Potassium.
• Treatment: Rapid infusion of normal saline (10-20 mL/kg)
over 20-30 minutes. Repeat another bolus if features of
hypovolemia persist.
If no response with two blouses,Albumin infusion (5%
Albumin at 10-15 mL/kg or 20% Albumin at 0.5-1 g/kg) is
given. Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
32. Infections
Children with nephrotic syndrome are prone to develop
infections because of:
• Low IgG levels
• ImpairedT-lymphocyte function
• Edema fluid acting as potential culture medium
• Impaired tissue perfusion due to edema
• Low factor B (C3 pro-activator) & Factor D levels -
decreased bacterial opsonization
• Immunosuppressive therapy
• Skin breaks due to stretching of edematous skin, are easy
portal of entry for organisms.
ESR, leukocyte count are poor markers of infection in
nephrotic syndrome. CRP, pro-calcitonin can be helpful
instead. Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
33. Infections contd.
Spontaneous bacterial peritonitis:
• Streptococcus pneumoniae is the most common cause.
Streptococcus pyogenes, gram negative organisms (E.coli,
Hemophilus) are the other causative organisms.
• Presentation:Abdominal pain, nausea, vomiting, fever,
diarrhea, tenderness & rigidity.
• Other causes of abdominal pain in nephrotic syndrome:
splanchnic ischemia due to hypovolemia & gastritis due to
steroid intake.
• Diagnosis: Examination of ascitic fluid (hazy/turbid),
presence of leukocytes (>75-100/mm3) with >50%
neutrophils & culture.
• Treatment: IV Ampicillin and Aminoglycoside or
monotherapy with IV Ceftriaxone for 7-10 days.
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
35. Infections contd.
Tuberculosis:
• Mantoux test is to be done before starting steroid
therapy.
• Those with Mantoux positive but show no evidence of
TB, should receive INH prophylaxis (10 mg/kg/day) for
6 months.
• Those showing evidence of active tuberculosis should
receive standard anti-tubercular therapy.
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
36. Infections contd.
Varicella:
• Varicella may be a severe illness in patients with nephrotic
syndrome receiving corticosteroids or other
immunosuppressive drugs.
• Susceptible patients (unimmunized / no history ofVaricella),
who are exposed to a case of chickenpox should therefore
receive a single dose of Varicella Zoster Immunoglobulin
(VZIG) or 400 mg/kg Intravenous Immunoglobulin (IVIG)
within 96 hr of exposure.
• Patients who develop varicella should receive intravenous
acyclovir (1500 mg/m2/day in 3 doses) or oral acyclovir (80
mg/kg/day in 4 doses) for 7-10 days.
• The dose of prednisolone should be tapered to 0.5
mg/kg/day or lower during the infection.
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
37. Stress doses of corticosteroids
• Children who have received high doses of
corticosteroids (>1mg/kg daily) for more than 2 weeks
in the past year are at risk of HPA (hypothalamo-
pitutary-adrenal) axis suppression.
• Such children, during the periods of stress (infection,
surgery & anesthesia) should be given,
IV hydrocortisone at 2-4 mg/kg/day, followed by
Oral Prednisolone 0.3-1 mg/kg/day
– for the duration of stress and then tapered rapidly.
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
38. Immunization
• Patients receiving prednisolone at a dose of 2
mg/kg/day or greater, or total 20 mg/day or greater for
more than 14 days are considered
immunocompromised.
• Such patients should not receive live attenuated
vaccines; inactivated or killed vaccines are safe.
• Live vaccines can be administered once the child is off
immunosuppressive medications for at least 4 weeks.
• Administration of some vaccines, e.g., Hepatitis B,
Measles-Mumps-Rubella or Meningococcal vaccines
may rarely precipitate a relapse.
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
39. Immunization contd.
PneumococcalVaccines:
• Children below 2 yr of
age
2-4 doses of the heptavalent conjugate
pneumococcal vaccine
• Previously
unimmunized children
between 2-5 yr
A priming dose of the conjugate vaccine
should be followed 8 weeks later, by the 23-
valent polysaccharide vaccine.
• Children older than 5 yr
Only a single dose of the polysaccharide
vaccine.
Revaccination after 5 yr is considered for children (<10-yr-old) with active
nephrotic syndrome.
Varicella vaccine:
Patients in remission and not on immunosuppressive therapy should
receive the varicella vaccine.
12 months and 12 yr of age – Single dose
13 yr or older – 2 doses separated by an interval of at least 4 weeks
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
40. Thromboembolism
• Incidence 2-5%. More common in steroid resistant nephrotic
syndrome than steroid sensitive nephrotic syndrome.
• Venous thrombosis more common than arterial thrombosis.
• Predisposing factors:Urinary loss of Anti-Thrombin III, protein C,
protein S; elevated Fibrinogen levels; volume depletion caused by
diuretic therapy or diarrhea; immobilization.
• Renal vein thrombosis:Oligoanuria, hematuria, flank pain
• Saggittal sinus & cortical vein thrombosis: Convulsions, vomiting,
altered sensorium and neurologic deficits.
• Femoral vein thrombosis, mesenteric vein thrombosis & deep vein
thrombosis leading to pulmonary embolism can occur.
• Diagnosis:USG, Doppler studies and MRI.
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
41. Thromboembolism contd.
• Management: Correction of dehydration, IV Heparin or SC
LMWH initially followed by oral-anti coagulants on the long
term.
• Prevention:Avoid prolonged bed rest, maintenance of
hydration, avoid injudicious use of diuretics
• Prophylactic anti-coagulant therapy such as low dose aspirin
is not routinely recommended in nephrotic syndrome.
• Prophylactic anti-coagulant therapy can be given in the
setting of:
• Previous history of thromboembolism
• An underlying hypercoagulation disorder other than
nephrotic syndrome
• Presence of a central venous catheter
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
42. Thromboembolism contd.
• Management: Correction of dehydration, IV Heparin or SC
LMWH initially followed by oral-anti coagulants on the long
term.
• Prevention:Avoid prolonged bed rest, maintenance of
hydration, avoid injudicious use of diuretics
• Prophylactic anti-coagulant therapy such as low dose aspirin
is not routinely recommended in nephrotic syndrome.
• Prophylactic anti-coagulant therapy can be given in the
setting of:
• Previous history of thromboembolism
• An underlying hypercoagulation disorder other than
nephrotic syndrome
• Presence of a central venous catheter
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
43. Hyperlipidemia
• Hyperlipidemia in nephrotic syndrome is
characterized by elevated LDL, IDL,VLDL and
Lipoprotein (a). HDL levels are reduced or unchanged.
LDL/HDL ratio is increased.
• Mechanism: Hypoalbuminemia upregulates HMG-CoA
reductase and downregulates lipoprotein lipase,VLDL
receptor and hepatic triglyceride lipase.
• In steroid sensitive nephrotic syndrome,
hyperlipidemia is associated with relapse and lipid
levels fall once remission is achieved.
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
44. Hyperlipidemia contd.
• Patients with steroid resistant nephrotic syndrome
with frequent relapses and persistent proteinuria tend
to have continued dyslipidemia and require drug
therapy.
• Management:
Dietary fat should be restricted to <30% of calories.
Saturated fat should be <10% of total calorie intake.
Dietary cholesterol intake should be <300 mg/day.
When dietary modification is not effective, HMG-CoA
reductase inhibitors (Atrovastatin) can be used.
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
45. Hypertension
• Hypertension may be present at the onset or may
appear late due to steroid toxicity.
• Goal is to maintain blood pressure to <90th percentile
of normal.
• Management:
Low salt diet, exercise, weight reduction.
ACE inhibitors and Angiotensin Receptor Blockers
are the first line agents as they also reduce
proteinuria.
Calcium channel blockers and β2 agonists can also be
used.
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
46. Education of parent
• Parents should be provided information about the
course, complications & outcome of the disease.
• Urine examination with dipstick or by boiling method
at home. Daily during relapse or during periods of
infection. Once or twice a week during remission.
• Maintain a dairy containing information about
proteinuria, medications & infections.
• Ensure that the child participates in all activities and
sports during periods of remission. No restrictions are
imposed.
• As infections constitute significant proportion of
morbidity, need for appropriate immunization should
be stressed.
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
48. Onset with in 3 months of life
Congenital nephrotic
syndrome
Onset after 3 months of life
but before 1 year of life
Infantile nephrotic syndrome
Onset after 1 year of life
Childhood nephrotic
syndrome
Most common varieties of congenital nephrotic
syndrome are:
• Finnish type due to Nephrin gene (NPHS1) mutation
&
• Diffuse mesangial sclerosis due to Wilms tumor
suppressor 1 (WT1) gene mutation.
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
50. Clinical features
• Proteinuria starts in-utero
• Born premature with large placenta (Weight of placenta
>25% of birth weight of the baby)
• Edema soon after birth, abdominal distension, umbilical
hernia, wide cranial sutures and fontanelle
• Failure to thrive, delayed development, hypothyroidism,
repeated infections, spontaneous vascular thrombosis
• Prone for both hypotension and hypertension
• Galloway Mowat syndrome: Hiatal hernia, microcephaly,
psychomotor retardation, hypotonia and seizures.
• Pierson syndrome: Microcoria
• Denys Drash syndrome:Ambiguous genitalia
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
51. Investigations
• Nephrotic range proteinuria
• Low serum albumin
• ElevatedTSH
• Dyslipidemia (Elevated
triglycerides, elevated LDL
cholesterol & low HDL
cholesterol)
• Deranged renal function is
seen beyond infancy
• Typical features are seen in
renal biopsy done at 3-8
months of age
• USG findings depend on the
age. (Kidney size is normal
and corticomedullary
differentiation is intact till 2
months of age)
• TORCH serology to detect
congenital infections
Prenatal Diagnosis:
• Prenatal genetic testing by
amniocentesis or chorionic
villous biopsy to detect
mutations
• Elevated AFP in amniotic
fluid
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
52. Management
• Goals:To provide good nutrition, control edema, prevent
thrombosis, prevent infection and allow the child to reach
weight (9Kg) suitable for renal transplantation.
• Immunosupression has no role in the management of
congenital nephrotic syndrome.There may be response to
appropriate antimicrobial therapy for congenital syphilis
and toxoplasmosis.
• Nutritional support:
• Calories 130 kc/kg/day
• Proteins 4 g/kg/day
• Vitamin D2 400 IU/day
• Vitamin E 2.5 - 3.0 mg/day
• Magesium
40-60 mg/day in the absence of renal
failure
• Calcium
500 mg/day for <6 months
750 mg/day for 6-12 months
1000 mg/day for >12 months Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
53. Management contd.
• Aggressive control of edema: By usage of loop and thiazide
diuretics.Albumin infusion (3 to 4 g/kg/day) with
Furosemide 0.5 mg/kg/day may be needed for refractory
edema.
• Thyroxine supplements:Thyroxine (6.25-12.5 μg/day)
adjusted toTSH levels to control clinical or subclinical
hypothyroidism
• Reduction of proteinuria:
o ACE inhibitors: Captopril 3-4 mg/kg/day or Enalapril 0.2-
0.5 mg/kg/day
o Indomethacin: 1-2 mg/kg/day
o Unilateral nephrectomy
o Bilateral nephrectomy with continuous peritoneal
dialysis
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
54. Management contd.
• Anticoagulant therapy: Low dose Aspirin or Dipyridamole
and Warfarin to keep PartialThromboplastin Time (PTT) at
20% to 30% of normal.
• Control of infections: Prophylactic use of antibiotics is not
required but even minor infections need to be treated
promptly.
• Renal transplantation: Done once the child reaches 9 Kg of
weight.
Recurrence in transplanted kidney may respond to Steroids,
Cyclophosphamide, Plasma Exchange or Rituximab (Anti-
CD20).
Prognosis: Patient survival after 5 years is >90%. Graft
survival after 5 years is >80%.
Due to the risk of chronic allograft nephropathy, second
transplantation is inevitable when these patients become
young adults. Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati
55. References:
• NelsonTextbook of Pediatrics – 19th edition
• IAPTextbook of Pediatrics – 5th Edition
• Indian Society of Pediatric Nephrology - Guidelines on
the management of steroid sensitive nephrotic
syndrome 2008
• Indian Society of Pediatric Nephrology - Guidelines on
the management of steroid resistant nephrotic
syndrome 2009
• Principles and Practice of Pediatric Nephrology by M.
Vijaykumar, B.R. Nammalwar – 2nd Edition
• Pediatric Nephrology – R.N. Srivastava & Arvind Bagga
– 5th Edition
Dr Naveen Kumar Cheri
S.V. Medical College, Tirupati