The document provides an overview of nephrotic syndrome, detailing its characteristics, epidemiology, pathophysiology, etiology, and types. It discusses the mechanisms of proteinuria, edema formation, hyperlipidemia, and hypercoagulability, as well as management strategies including dietary considerations, medication protocols, and complications associated with the condition. The content also outlines specific types of nephrotic syndrome such as minimal change nephrotic syndrome and focal segmental glomerulosclerosis, along with their clinical presentations and treatment approaches.

1. WELCOME
TO
SEMINAR

2. NEPHROTIC
SYNDROME
PRESENTED BY-
DR. SYED KAMRUL HASAN
IMO, DEPARTMENT OF PAEDIATRICS,
JRRMCH, SYLHET

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

5. PATHOPHYSIOLOGY

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

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

13. ETIOLOGY

14. Idiopathic Nephrotic Syndrome: (90%)
a. Minimal change nephrotic syndrome (85%)
b. Focal segmental glomerulo-sclerosis (10%)
c. Mesangial proliferation (5%)

15. Secondary Nephrotic Syndrome : (10%)
 Infection : Hepatitis B & C, HIV, malaria, syphilis,
toxoplasmosis, cytomegalovirus(CMV), bacterial
endocarditis
 Drugs : Penicillamine, Gold, NSAIDS, Interferone,
Lithium, Captopril, Mercury, Phenidione.
 Allergic Disorder : Bee sting, Food allergens
 Malignant Disease : Chronic lymphocytic
leukaemia, Hodgkin’s lymphoma
 Systemic disease : SLE, HSP, Amyloidosis,
Polyarteritis , Diabetes mellitus

16. Congenital Nephrotic Syndrome : Rare
Finnish Type
Denys Drash Syndrome

17. MINIMAL CHANGE NEPHROTIC SYNDROME

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.

20. Minimal Change
Nephrotic Syndrome

22. FOCAL SEGMENTAL GLOMERULOSCLEROSIS

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.

25. MESENGIAL PROLIFERATION

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.

28. CONGENITAL NEPHROTIC SYNDROME

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.

30. Causes of congenital nephrotic syndrome:
 Classic' Finnish 'type.
 Diffuse mesangial sclerosis -
*with pseudohermaphroditism (Denys-Drash
syndrome).
*with microcephaly ,development delay and hiatal
hernia(Galloway-Mowat syndrome).
*idiopathic.
 Primary focal segmental glomerulosclerosis
 Congenital infections : cytomegalovirus, syphilis,
rubella, toxoplasma, hepatitis B.

31. FINNISH TYPE CONGENITAL
NEPHROTIC SYNDROME

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.

34. Relation of edema with hypoalbuminaemia :
Serum albumin Oedema
20 - 25 gm/l Periorbital oedema
18 - <20 gm/l Dependent oedema
15 - < 18 gm/l Ascites
< 15 gm/l Genital oedema

35. Heat Coagulation Test

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

38. Terminology Related To
Nephrotic Syndrome

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.

43. INVESTIGATION

44. For diagnosis :
- Urine R/M/E ( 3+ or 4+ proteinuria , granular &
hyaline casts)
- Spot urine protein creatinine ratio (>2.0)
- 24 hours urinary total protein (>1gm/m2/day )
- Serum albumin (<2.5 gm/dl)
- Serum cholesterol (> 250mg/dl )

45. For infection screening :
- CBC
- Blood culture
- Urine culture
- Chest X -ray
- HBsAg
- MT

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

48. MANAGEMENT

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

54. DAILY ACTIVITIES
 Physical activity as tolerated
 May attend school

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

76. COMPLICATIONS OF
NEPHROTIC SYNDROME

77. Complication related to disease :
1.Infections:
 UTI
 Pneumonia
 Spontaneous bacterial peritonitis
 Cellulitis
 Septicemia
 Meningitis
 Bone & joint infection
 Flair up of tuberculosis
 Varicella, Measles

78. 2. Thromboembolism :
 Deep vein thrombosis
 Renal vein thrombosis
 Pulmonary vein thrombosis
 Cerebral venous sinus thrombosis
3. Hypovolumia & shock
4. Hypocalcaemia
5. Diarrhea & vomiting
6. Acute renal failure
7. Anaemia

79. 8. Abdominal pain due to :-
Peritonitis,
Mesenteric ischaemia,
UTI,
Renal vein thrombosis,
Steroid induced gastritis

80. COMMON ORGANISM CAUSING INFECTION IN
NEPHROTIC SYNDROME
Bacterial :
Streptococcus pneumoniae
Haemophilus influenzae
E.coli
Klebsiella
Pseudomonas
Mycobacterium tuberculosis
Virus :
Measles
Varicella

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.

83. Complication due to drug

84. STEROID
 Cushingoid face
 Obesity
 Cataract
 Buffalo hump
 Hypertension
 Avascular necrosis
 GF
 More chance to develop infection
 Osteoporosis
 Hyperglycaemia
 Peptic ulcer

85. Low hair line
Cataract
Facial Plethora
Buffalo Hum
Gynaecomashia
Stria
Hypertension
Abdominal fat

86. WHAT TO DO?
Stop steroid when toxicity develop
Go for Alternative drug
Counseling the parents

87. CYCLOPHOSPHAMIDE
Side effect:
 Neutropenia
 Disseminated varicella
 Reversible alopecia
 Hemorrhagic cystitis
 Sterility
 Risk of future malignancy

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.

89. CYCLOSPORINE
Side effect:
Hypertension
Nephrotoxicity
Hirsutism
Tremor
Gum hypertrophy
What to do?
Blood level of urea creatinine should be measured
every 4-6 weeks.

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