Nephrotic syndrome is a clinical state characterized by : Massive proteinuria ( > 40 mg /m²/hour), Hypoalbuminaemia ( < 2.5 gm/dl), Generalized edema, Hyperlipidemia ( S. cholesterol >250 mg /dl). 60%-80% present before 6 years. MCNS most commonest type of nephrotic syndrome , about 85% of idiopathic nephrotic syndrome.
3. What is Nephrotic syndrome ?
Nephrotic syndrome is a clinical state characterized by :
Massive proteinuria ( > 40 mg /m²/hour)
Hypoalbuminaemia ( < 2.5 gm/dl)
Generalized edema
Hyperlipidemia ( S. cholesterol >250 mg /dl)
4. EPIDEMIOLOGY :
2-7/lac, <16 years
In Asia, 7-16/lac, < 16 years
60%-80% present before 6 years
MCNS – M:F 2:1,
Median age 2 and half years
FSGS- M:F 1.3:1
6. Mechanism of proteinuria :
Proteinuria results from an increase in glomerular
capillary wall permeability. The cause of the
increased permeability is not well understood.
It may be due to :
T cell dysfunction
Plasma Permeability factor
Mutation of genes
7. T cell dysfunction
Alteration of cytokines
Increase IL4 & IL13
Podocytes express receptors for IL4 & IL13
& become Activated
Disruption of Glomerular physiology
Loss of negatively charged glycoproteins within the glomerular
capillary wall
8. Plasma Permeability factors
Permeability factors are present in circulations and they
increase glomerular permeability in MCD and FSGS.
Important permeability factors are – Vascular endothelial
growth factor (VEGF) and Heparanase.
VEGF-produced by glomerular podocytes and receptors for
these factors are located on glomerular endothelial cell and
mesangial cells
9.
10. Mechanism of edema formation :
Massive urinary protein loss
Hypoalbuminaemia
Decrease plasma oncotic pressure
Transudation of fluid
from intravascular space
to interstitial space
Oedema
Because of the low plasma oncotic
pressure , reabsorbed Na+ & water
Are lost into the interstitial space
Decrease intravascular
Volume
ADH release
Reabsorption of
water in collecting
ducts
Decrease
intrvascular volume
↓ Renal perfusion
Activation of renin
angiotensin
aldosterone system
Distal tubular
reabsorption of Na+
and H2O
11. Mechanism of hyperlipidemia :
The hypoproteinaemia stimulates generalized protein
synthesis in the liver including lipoproteins.
Lipid catabolism is diminished due to decrease plasma
lipoprotein lipase which is lost through urine.
12. Mechanism of hypercoagulability :
A. Increase prothrombotic factor :
Haemoconcentration due to hypovolumia, abuse of diuretics,
dehydration
Increase fibrinogen
Impaired fibrinogenolysis
Thrombocytosis
Relative immobilization
B. Decrease fibrinolytic factor :
Increase urinary loss of protien C,S, antithrombin III
18. • Most commonest type of nephrotic syndrome ,
about 85% of idiopathic nephrotic syndrome.
• Common in male than female (2:1).
• Common in between 2-6 years of age.
• Usually present with mild oedema, initially noted
around the eyes with times oedema become
generalized with development of ascites, pleural
effusion & genital oedema.
• Anorexia, irritability, abdominal pain & diarrhoea are
common.
• Hypertension & gross haematuria are uncommon.
• Bed side heat coagulation test +++/++++
19. • In light microscopy: No appreciable glomerular
pathology is noted.
• Immunofluroscence microscopy : Typically negative.
• In electron microscopy: Effacement of foot processes
of podocytes in glomerular basement membrane.
• More than 95% response to steroid but high
tendency to relapse.
23. • About 10% of idiopathic nephrotic syndrome.
• Occurs in older children.
• Male female ratio 1.3:1.
• The clinical profile is similar to MCNS, though
microscopic hematuria & hypertension may be
present.
• Only 20% response to steroid.
24. • On light microscopy : shows mesangial
proliferation & segmental scarring.
• On immunofluroscence microscopy : shows IgM
& C3 staining in the area of segmental sclerosis.
• On electron microscopy : shows segmental
scarring of glomerulus tuft with the obliteration of
the glomerular capillary lumen.
26. o Usually occurs in older children.
o Male & female are equally affected.
o The clinical profile is similar to MCNS with
haematuria & hypertension.
o About 50 % response to steroid.
27. o On light microscopy : shows diffuse increase in
mesangial cell & matrix.
o Immunofluroscence microscopy : shows slight
deposition of IgM in mesengial cell.
o Electron microscopy : shows increse number of
mesengial cells & matrix as well as effacement of
the epithelial cell foot process.
29. Nephrotic syndrome is present at birth or appears
within three months of life.
Renal biopsy should be performed in all cases.
The commonest form is the autosomal recessive
Finnish nephrotic syndrome due to defective
production of Nephrin.
There is no specific therapy, appropriate supportive
care is instituted.
32. The Finnish type congenital nephrotic syndrome is
an autosomal recessive disease.
Infants with the Finnish type of congenital nephrotic
syndrome are born prematurely, often with large
placenta.
Nephrotic syndrome is present at or soon after birth.
33. Clinical presentation:
Failure to thrive,
Repeated infection,
Delayed development,
Ascites,
Spontaneous vascular thrombosis.
Biopsy shows cortical microcysts, representing
dilated proximal convoluted tubules, glomeruli may
show mesangial proliferation and increased
mesangial matrix.
36. Interpretation of HCT :
Keep the tube in front of newspaper
Read newspaper Amount of protein
mg/dl
Clearly read Trace 10-20
Can read but with
difficulty
+ 30-100
Can’t read , only
see writing
++ 100-300
Only paper is seen +++ 300-1000
Nothing is seen ++++ >10000
39. Remission:
Protein free urine (urinary protein excretion <4mg /
m² /hr or urine protein negative/trace) for 3
consecutive days.
Relapse :
Proteinuria (urinary protein excretion > 40 mg/ m² /hr
or urine protein +++ or more) for 3 consecutive days
( plus edema), in a patient having previously in
remission .
40. Frequent relapse :
When relapses ≥ 4 times in a 12 months period (who
respond previously with prednisolone therapy).
Infrequent relapse :
When ≤ 3 relapses in a 12 months period (who
respond previously with prednisolone therapy).
41. Steroid dependent :
Patient relapse while on alternate day steroid therapy
or within 28 days of completing a successful course
of prednisolone therapy.
Steroid resistant :
Children who failed to respond to prednisolone
therapy within 8 weeks of therapy are termed steroid
resistant.
42. Late responder :
Patient with initial resistance who responds
later.
Late resistance :
Initial responder who subsequently fails to
respond to steroid therapy.
46. To exclude secondary nephrotic syndrome :
-Serum creatinine
-Serum C3, C4
-Serum electrolyte
-For cause identificatin :
HBsAg, Anti HCV
ANA, Anti ds DNA
HIV screening
VDRL
Renal USG
Renal biopsy
47. Renal biopsy
Indication :
Age of onsent < 1 year or >12 years
Haematuria
Sustained hypertension
Renal failure
Persistent ↓C3 ,C4
Steroid resistance nephrotic syndrome
Suspected secondary cause of nephotic
syndrome
Before cyclosporine or tacrolimus therapy
49. Criteria for hospital admission :
First attack ( for counseling)
With complications
Need for renal biopsy
Doubtful compliance
50. Aim of management :
Achieve remission
Prevention of relapse
Avoidance of complications & side effects
of drugs
51. Treatment of Nephrotic Syndrome
Supportive & Symptomatic management
Specific management
Prevention and treatment of complications
52. Supportive & symptomatic treatment:
Dietary management & daily activities
Control of oedema
Prevention and treatment of infections
Counseling of parents and psychosocial support.
53. Dietary Management
A balance diet, adequate in protein and calories
Protein : An adequate protein intake (1.5-2
gram/kg/day)
Patient with persistent proteinuria should
receive 2-2.5gm /kg/day.
Fat : <30% of the diet
Supplements vitamins and minerals
Salt intake restricted up to remission
55. Management of Oedema :
Mild to moderate oedema :
Salt restriction up to remission
No fluid restriction no diuretics
56. Massive oedema :
Salt restriction
Fluid restriction
Diuretics :
Oral frusemide (1-3mg/kg) in 1-3 divided
doses or iv 4-10 mg/kg /day.
Spironolactone (1-3mg/kg/day) added in
case of higher or prolonged duration of
treatment.
57. Hydrochlorthiazide (1-3 mg/kg/day) or
metolazone (0.1-0.5 mg/kg/day) may be
added with frusemide in severe case.
I/V 20 % human albumin (0.5-1 gm /kg
/dose over 1-2 hours) when fluid restriction
& diuretics are not effective.
58. Indication of albumin infusion in NS :
Serum albumin < 1.5 gm/dl
Oedema not improve even after maximum
dose of diuretics
Child with signs of hypovolumia
Severe complication of diuretic therapy
59. Prevention & treatment of infection by
appropriate antibiotics
60. Specific Management for
First Attack
Relapse
Steroid dependent nephrotic syndrome
Steroid resistant nephrotic syndrome
Frequent relapse
Infrequent relapse
61. First attack
Prednisolone :
60mg/m2/day (max. 80mg) 2-3 divided doses
for 6 weeks. Then
40mg/m2/every alternate day – single morning for
dose for 4 weeks. Then slowly tapered &
discontinued over the next 4-8 weeks.
62. Relapse
Prednisolone :
60mg/m2/day - till urine become protein free for 3
consecutive days.
Followed by 40mg/m2/every alternate day single
morning for dose for 4 weeks & gradually
tapered over 4-8 weeks
63. Alternative drugs used in Nephrotic
Syndrome :
o Levamisole
o Cyclophosphamide & chlorambucil
o Cyclosporine
o Mycophenolate mofetil
o Tacrolimus
o Methyl prednisolone
64. Frequent relapses /
Steroid dependennce
Prednisolone– 60 mg /m²/ day till remission then
Alternate day prednisolone to maintain remission
Steroid threshold
<0.5 mg/kg on
alternate day
Alternate day
prednisolone
for 9-18 months
Threshold >0.5 mg/kg on
alternate day or
Severe complication, or
steroid toxicity
Levamisole ,
Cyclophosphamide,
Tacrolimus,
Cyclosporin A,
Mycophenolate mofetil
65. Frequent relapses & Steroid dependence :
Following treatment of a relapse, prednisolone is
gradually tapered to maintain the patient in remission
on alternate day dose of 0.5 mg/kg, which is
administered for 9-18 months. If the prednisolone
threshold to maintain remission is higher or if
features of steroid toxicity are seen, additional use of
the following immunomodulators are suggested :
66. Levamisole :
2-2.5 mg /kg on alternate days for 12-24 months.
Prednisolone 1.5 mg/kg on alternate days for 2-4
weeks.
Gradually reduced by 0.15-0.25 mg/kg every 4 weeks
to a maintenance dose of 0.25-0.5 mg/kg that is
continued for 6 or more months.
67. Cyclophosphamide :
2-2.5 mg/kg for 12 weeks
Prednisolone 1.5 mg/kg on alternate days for 4 wks.
Followed by 1mg/kg for next 8 weeks.
Steroid therapy tapered & stopped over the next 2-3
months.
68. Cyclosporine (CsA) :
4-5 mg/kg daily for 12-24 months
Prednisolone 1.5 mg/kg on alternate days for 2-4
weeks .
Gradually reduced by 0.15-0.25 mg/kg every 4 weeks
to a maintenance dose of 0.25-0.5 mg/kg that is
continued for 6 or more months.
69. Tacrolimus :
0.1-0.2 mg/kg daily for 12 – 24 months.
Mycophenolate mofetil (MMF) :
20-25 mg/kg/day 12 hourly for 12-24 months
tapering doses of prednisolone for 12 -24 months.
70. Adjunct therapy :
ACE inhibitor
Angiotensin II blocker
These drugs causing efferent arteriolar dilation &
reducing glomerular filtration pressure & thus
reducing proteinuria in steroid resistant nephrotic
syndrome.
71. Rituximab:
Is an anti CD-20 monoclonal antibody
1-2 dose Rituximab significantly reduces relapse
rate in FRNS and SDNS
Dose : 375 mg/m2 i.v infusion
72. Steroid Resistance Nephrotic Syndrome :
The choice of therapy in steroid resistant nephrotic
syndrome include:
calcineurin inhibitors with alternate day prednisolone,
IV methylprednisolone followed by cyclophosphamide
or cyclosporine.
Angiotensin converting enzyme inhibitors and
angiotensin receptor blockers reduce the intensity of
proteinuria.
Hypertension should be controlled, aiming to achieve
reduction of blood pressure to the 50th percentile.
Statins are used to control hyperlipidaemia
73. Treatment protocol of steroid
resistant NS of BSMMU
Failure to remission after 8weeks of prednisolone
therapy(60mg/m2)
Do renal biopsy and if it is MCNS with steroid resistant
Oral cyclosporin (100mg/m2/day) or
Tacrolimus (50-70mg/day) plus
alternate day prednisolone(1.5mg/kg/day) for 1-2 years.
74. Another protocol-
Pulse methylprednisolone (20-30mg/kg)alternate
day for 5-6 days followed by tapering dose of oral
prednisolone (1.5mg/kg) every alternate day for 1-
2 years.
For other than MCNS with steroid resistant
Injection cyclophosphamide (500mg/m2/month) for
6 months plus alternate day prednisolone
(1.5mg/kg) for 1-2 years.
75. CONGENITAL NEPHROTIC SYNDROME
• There is no specific treatment
• The disease is resistant to corticosteroid &
cytotoxic drugs.
Nephrectomy
Dialysis up to weight 10 kg or 1 year of age
Renal transplantation
81. Prevention of infection
Immunization:
Administration of live vaccines measles,
mumps, rubella, oral polio, varicella is avoided
until steroid therapy discontinued for 4 weeks.
Other vaccines pneumococcal, Hib, Hepatitis
B may be given.
Patient in remission should receive the
varicella vaccine.
82. If the child with nephrotic syndrome is on
continuous immunosuppression , siblings
should receive the inactivated polio vaccine
instead of OPV.
Siblings can safely receive the MMR &
varicella vaccines without a risk of
exposing the patient to the attenuated
viruses.
88. What to do?
- Blood count –weekly during the first 4 weeks
of treatment than 2 weekly.
-If TC of WBC <5000/ cmm –drug is withheld
till normal
-Maintain high urine output to prevent
hemorrhagic cystitis and use MESNA ( sodium 2-
mercaptoethane sulfanate ) if iv cyclophosphamide
given.
90. LEVAMISOLE
Side effect:
GIT upset
Influenza like symptoms
Skin rash may associated with leukocytoclastic
vasculitis
Neutropenia
Liver toxicity
Convulsion
91. What to do?
Monitor blood leucocyte count for every 2-
4 month
All the side effect diminishes after drug
withdraw
92. Tacrolimus :
Side effect :
Septicemia
Cardiac damage
Hypertension
Hepatotoxicity
Nephrotoxicity
Electrolyte imbalance
Hyperglycemia
What to do ?
Blood level of creatinine & glucose should estimated
every 2-3 months
93. SOME SPECIAL SITUATION
NS WITH TB:
Clinical feature
low grade fever
persisting cough
Investigation:
Chest X-Ray
MT
Treatment:
At first start anti tubercular drugs , after 2 weeks
start prednisolone therapy.
94. NS WITH VARICELA
Treatment:
oral acyclovir 80 mg/kg daily in 4 divided dose for 7-
10 days.
Patient exposed to varicella:
VZIG 125 unit/10 kg body weight ( minimum
125unit , maximum 625unit) should be given within
96 hours of significant exposure.
Intravenous immunoglobulin 400mg/kg may be
used.
95. NS WITH HEPATITIS B
Lamivudin 2 week before steroid given &
continue 6 weeks to 6 month after the end
of the treatment.
Interferon should also be given.
96. NS WITH MEASLES
Measles causes a serious danger to
patients receiving steroid & cytotoxic drug.
NS less than <1 year is uncommon , so
most patients are already vaccinated
before they get NS.
After 2 weeks start prednisolone therapy.
97. COUNSELING
Should be trained how to test urine for albumin &
maintain a diary.
Parents should be explained about the naturel
history of the disease.
Should be provided with a booklet covering all
information about the condition.
Normal activity & schooling
Parents compliance & co operation is essential.
98. Prognosis :
Depends on whether the patient is steroid
responsive or resistant.
In Steroid sensitive Nephrotic Syndrome:
The final outcome is excellent . Most of the patient
stop getting relapses between the age of 14-20 years
without any residual renal dysfunction. The
subsequent course of steroid responsive NS are-
25-40% have infrequent relapse
40% have frequent relapse
20% steroid dependence
99. In Steroid resistant Nephrotic Syndrome :
Generally have much poorer prognosis.
Develop ESRD over 10 years requiring dialysis
& or transplantation.
100. FOLLOW UP
During hospital admission:
Daily- Vital signs,
- Weight
- Fluid intake
- Urine out put
-Abdominal girth
-Edema
-Any sign of infection
.
101. During discharge:
Mother should know when to return
If the child develop edema with any sign of
infection such as fever, cough, diarrhea,
vomiting then mother should test urine for
albumin.
If the urine for albumin 3+ or more for 3
consecutive days then she must return to
the hospital.
102. BAD PROGNOSTIC SIGNS OF NS
Very young (<1 yr) & (>10yr)
Persistent heavy hematuria
Hypocomplementemia
Hypertension
Renal failure
No Response within 28 days of adequate
prednisolone regimen