Guess the

diagnosis?
Guess the
diagnosis?
NEPHROTIC
SYNDROME
Dr TRIPTI SRIVASTAVA
MD PAEDIATRICS
AP
DEPARTMENT OF PEDIATRICS
VCSG INSTITUTE OF MEDICAL SCIENCES
  HOPI:
Mayank, a 6-year old male child, hindu by religion s/o Ashish
Kumar, resident of village- Vyaschatti, distict Pauri Garhwal was

CASE admitted in Pediatrics ward of HNB Base Hospital Srinagar on 18

July 2022 with complaints of:
SCENARIO I
1. Swelling over face× 3 days

2. Fever×1 day
3. Loose stools (3 episodes )×1 day
  As stated by the patient’s attendant( father ), he was apparently
asymptomatic 3 days back when he started developing swelling
around eyes and face which was progressive and increased to
extend up to abdomen. There was no history of diurnal variation.
HOPI  The patient also developed fever 1 day back, acute in onset,
continuous , not documented, not associated with chills or rigor.
 The patient also had 3 episodes of loose stools, watery in
consistency , not associated with blood or mucous.
  No history of vomitings, cough, sore throat,difficulty in breathing,
palpitations, chest pain,bluish discoloration
 No history of decease in urine volume and frequency
 No history of jaundice, blood in urine, burning micturition, cola
coloured urine.
HOPI  No history of headache, altered sensorium, seizures.
 No history of recurrent infection, skin rashes ,boils, joint pain,
weight loss.
 No history of drug intake.
 No history of insect bite.
  PAST HISTORY:
Patient presented with similar complaints in May 2021, was
admitted in this hospital diagnosed and treated as a case of
Steroid sensitive Idiopathic Nephrotic syndrome. Patient had
similar episode in May 2022,was admitted and treated in our
HISTORY hospital as first relapse.
FAMILY HISTORY:
No history of similar complaints in other family members.
No history of DM, TB, HTN , obesity,allergies ,asthma or any other
chronic renal illness.
No history of consanguineous marriage.
  ANTENATAL AND NATAL HISTORY :
Uneventful ( Term/AGA/ NVD/ immediate cry) G3P3L3A0
 DEVELOPMENTAL HISTORY:
Appropriate for age
 IMMUNISATION HISTORY:
Complete for age as per NIS
Pneumococcal, influenza and varicella vaccines not administered
after previous both episodes

HISTORY  PERSONAL HISTORY:

Normal bowel and bladder habits. Normal sleep wake cycle.
• SOCIOECONOMIC HISORY:
Middle class nuclear family,father is a shopkeeper, with 3 kids ,Patient is
second order child with 12 year old elder sister and a 3 year old younger
brother.
No overcrowding present, water supply from stream water, cooking
on gas stove ,pucca house with 4 rooms with adequate ventilation
and electricity supply, separate kitchen ,cattle shed 50 metres away and
separate washroom .
No mosquito breeding sites around house present.
 GENERAL EXAMINATION
Vitals were stable with-
HR-74/min
RR-28/min
BP = 108/60 mm Hg( between 50 -90 centile)
Temperature-101.8 degree f in axilla
SpO2- 98% on room air
EXAMINATION Anasarca-present in form of periorbital, facial puffiness and abdominal
distension, pitting type
Cyanosis-Not Present
Icterus- Not Present
Lymphadenopathy- Not Present
Clubbing- Not Present
No signs of dehydration present
 Observed Medi inference
an
weight 20 kg 19.3 50-90 centile
kg
height 111.5 cm 114,8 10-50 centile
cm
BMI 16.2 kg/m2 14.9 50-90 centile
kg/m2

ANTHROPOMETRY
 SYSTEMIC EXAMINATION

 ABDOMINAL EXAMINATION- soft, non tender, distended

abdominal girth 64 cm
EXAMINATION shifting dullness present
no visible pulsations or distended veins present.

• Other systemic findings were within normal limits.

  INVESTIGATIONS
Urine protein was 3+ for 5 days,
then 2+ for 3 days, 1+ for 3 days and negative on Day 13 by urine
dipstick.
Urine r/m- 10-12 pus cells/ hpf on Day 1, negative on subsequent
samples.
INVESTIGATIONS Serum albumin-1.3 g/dl
Hb-14 g/dl
WBC count-13940/cumm with 72% neutrophils
CRP-Negative
Blood and urine culture- Sterile on Day 5
LFT , KFT,S Cholesterol and serum electrolytes were within normal
limits.
  Patient was diagnosed as a case of Acute gastroenteritis with no
dehydration with Infrequently relapsing ( second relapse)
Idiopathic steroid sensitive nephrotic syndrome and treated
with iv antibiotics, antipyretics, antacids, oral probiotic , zinc
therapy , lasilactone, high protein diet, salt moderation and low
saturated fat diet.
 Fever and loose stools subsided within 24 hours of therapy and
TREATMENT swelling gradually subsided over 2 weeks.
 Patient was started on oral steroid therapy on day 5 of admission
@ 60 mg/ m2 BSA BD, not to be taken on empty stomach for 7
days.
 On discharge-Patients weight was 18.5 kg and vitals stable on Day
13 of tab. Prednisolone for 5 weeks (@ 40 mg/m2 BSA on
alternate days.
Parent counselling –
 explained about the disease, danger signs & usual
outcome
 Taught to examine protein in urine (by dipstick/boiling
test) 2-3 times per week in remission/ per day if infection
or oedema
 During remission , no dietary restriction
 Record of Medications
Patient was advised 2 doses of varicella 4-8 weeks apart, 1
dose of PCV and 1 dose of influenza vaccine 4 weeks after
completion of steroid treatment.
  Patient is now in remission and regular follow up monthly but not
FOLLOW UP taken vaccines.
  11 year old female patient Shivani, hindu by religion, daughter of
Mr. Ramesh Ram ,resident of Tharali, Chamoli. Informant was her
father. Patient presented to the emergency ward on 30/10/2022
with the chief complaint of:
CASE 1. Swelling over face since 4 week
SCENARIO II 2. Abdominal pain 15days back
3. Pain on deglutination 15 days back
  HOPI-
The patient was apparently asymptomatic 4 weeks back when
she developed undocumented fever which was sudden in onset ,
on/off in nature ,non progressive ,relieved by medication .On day
HOPI 2 of fever she developed swelling around the eyes which was
insidious in onset, gradually progressive in nature , increased
during morning and decreased during evening .started from pre-
orbital area then progressed over the face and then to abdomen ,
lower limbs over 4 weeks duration .
  Patient developed upper abdominal pain which was acute in onset,
non progressive in nature, non radiating started 15 days back
persisted for 3 days, no reliving or aggravating factor was present.
 Patient also developed pain on deglutination started 15 days back
which was acute in onset persisted for 2 days no aggravating factor
present relieved on medication .

HOPI  There is No h/o breathlessness on exertion , palpitaion, cyanosis, chest pain.

 No h/o jaundice , blood in urine, burning micturition.
 No h/o headache ,altered sensorium, seizures.
 No h/o recurrent infection, skin rashes , joint pain ,weight loss .
 No h/o vomiting, loose stools ,cough.
 No h/o of drug intake.
 No h/o insect bite .
  Past History-
No history of similar episode in the past.
 ANTENATAL AND NATAL HISTORY-
Uneventful( Term/AGA/ NVD/ immediate cry)
 DEVELOPMENTAL HISTORY-
Appropriate for age
HISTORY  IMMUNISATION HISTORY-
Complete for age as per NIS
• PERSONAL HISTORY- normal bowel and bladder habits.
Normal sleep wake cycle.
 • SOCIOECONOMIC HISORY:
Child belongs to lower middle class family a/c to modified BG
prasad scale, nuclear family of 4 member residing in pucca house
with 2 room separate kitchen and separate washroom adequate
HISTORY ventilation was present in the house water supply by
cooperation pipe line drinking water is stored in covered
container. There are no cattle or pet in the house. No mosquito
breeding site in the house and near the house.
 GENERAL EXAMINATION
 Patient was normally hydrated, appears puffy and has anasarca
with periorbital swelling and swelling over abdomen and lower
limbs with normal vitals.Oedema was pitting.
 ANTHROPOMETRY
EXAMINATION observed mean inference
Height 133cm 143.3 10th -25thperecentile
Weight 30kg 35.4kg 10th -25thperecentile
BMI 16.95 17.2 25th-50thperecentile
SYSTEMIC EXAMINATION
 ABDOMINAL EXAMINATION- soft, not tender, distended
abdominal girth-56 cm
Shifting dullness present
No visible pulsations or distended veins present.

• Other systemic findings were within normal limits.

 INVESTIGATIONS
Urine protein was 4+ for 3 days,
then 3+ for 9 days, 1+ for 2 days and negative on Day 14 by urine
heat coagulation test.
Urine r/m- Bacteria- Positive; 0-1 pus cells/hpf on Day 1, negative on subsequent samples.
Serum albumin-1.1 g/dl 2.1 g/dl (on day 10 of admission)
Hb-12.9 g/dl
WBC count-8400/cumm
CRP-Negative, ASO- Negative, Fever Profile- Negative
Blood culture- Sterile
Urine culture- E. coli sensitive to fosfomycin
LFT , KFT, serum electrolytes, Cholesterol and viral markers were within normal limits.
Koch’s Workup- Negative
ANA, Anti dsDNA, C3 were within normal limit
USG Abdomen- mild ascites
ECG- Sinus Bradycardia
XRAY Chest, 2d ECHO- WNL
 Patient was diagnosed as a case of Acute Urinary Tract infection
with Idiopathic steroid sensitive nephrotic syndrome and
treated with iv antibiotics, antacids, furosemide, high protein diet,
salt moderation and low saturated fat diet. Tab Enalapril was
added on Day 10 due to high blood pressure.
 Swelling gradually subsided over 2 weeks.
 Patient was started on oral steroid therapy on day 7 of admission
@ 60 mg/ m2 BSA BD, not to be taken on empty stomach for 6
weeks.
 On discharge-Patients weight was 27 kg and vitals stable on Day
17. Tab Prednisolone (for 5 weeks @ 60 mg/m2 BSA daily followed
by @40mg/m2/day alternate day) with Tab Envas and Antacid.
Parent counselling –
 explained about the disease, danger signs & usual
outcome
 Taught to examine protein in urine (by dipstick/boiling
test) 2-3 times per week in remission/ per day if infection
or oedema
 During remission , no dietary restriction
 Record of Medications
Patient was advised 2 doses of varicella 4-8 weeks apart, 1
dose of PCV and 1 dose of influenza vaccine 4 weeks after
completion of steroid treatment.
 Patient is now in remission and on regular follow up monthly but
not taken vaccines.
INTRODUCTION  Nephrotic syndrome consist of a group of symptoms
which is seen in any condition that seriously damages
INTRODUCTION
the glomerular capillary membrane , causing increased
glomerular permeability with loss of protein in urine.
MOST COMMON KIDNEY DISEASE IN CHILDHOOD
 Characterized by
1. Nephrotic range Massive Proteinuria
(40mg/m2/hr, 1gm/m2/24hrs, UP/UC Ratio
>2.0mg/mg)
2. Hypoalbuminemia <2.5 gm/dl (3 gm/dl a/c to
ISPN 2021)
3. Edema – pitting & soft
• Hyperlipidemia >200 mg/dl sometimes
• Hematuria & Hypertension occasionally present
NEPHRON
GLOMERULI
  1.2 to 16.9 cases per 100,000 children per year

 Higher in underdeveloped countries ( South east Asia )

INCIDENCE  Occurs at all ages but is most prevalent in children between the
ages 1.5-6 years.

 It affects more boys than girls, 2:1 ratio.

 In Adolescents ratio is same.

  Genetic –
a. Finnish type Congenital Nephrotic Syndrome
b. Focal Segmental Glomerulosclerosis
c. Diffuse Mesangial Sclerosis
d. Denys-Drash Syndrome
e. Nail – Patella Syndrome
f. Alport Syndrome
CAUSES g. Charcot-Marie-tooth disease
h. Cockayne syndrome
i. Laurence- Moon- Beidl-Bardet Syndrome
j. Galloway-Mowat Syndrome
 Idiopathic or Primary (>90% of all causes)
 Secondary
  Congenital – Oligomeganephronia (Renal Hypoplasia)
 Amyloidosis
 Infectious – Hepatitis (B,C) , HIV-1, Plasmodium malariae
Syphilis, Toxoplasmosis
 Inflammatory – Post Streptococcal Glomerulonephritis ,
IgA Nephropathy
SECONDARY  Immunological – Castleman Disease, Kimura Disease, Bee
CAUSES sting, Food allergens , SLE (butterfly rash , arthralgia) ,IgA
Vasculitis (HSP)(palpable purpura on extensor surfaces,
buttocks ,deranged kidney function, symmetrical
arthralgia/arthritis of long joints like hips, knees, abdominal
pain)
 Neoplastic – Lymphoma, Leukemia
 Traumatic ( Drug induced ) – Penicillamine , Gold,
NSAIDS, Pamidronate, Mercury, Lithium , Heroin use
  Based on Renal Histology -

1. Minimal Change disease ( >80 % )

RENAL
HISTOLOGY 2. Nephrotic Syndrome with Significant lesion-
 Mesangial proliferation(7-8%)

 Focal segmental Glomerulosclerosis (7-8%)

 Membranous Nephropathy(rare )

 Membranoproliferative glomerulonephritis
Features Minimal Lesion Significant Lesion
Age 2-6 years Older
Sex > In Boys Equal
Hematuria Minimal Usual
Edema Significant always Less significant
Blood Pressure Normal Normal or Increased
GFR Normal Normal or Decreased
Renal Biopsy
Light Microscopy- No significant Sclerosis in glomerular tuft
Immunoglobulin deposits / C3
Electron Microscopy- Non specific obliteration of foot
processes

Immunofluorescence- Mesangial IgM deposits

Serum C3 Normal Low in MPGN

Selectivity of Proteinuria High Low

Response to Steroids Remission in >95% Unsatisfactory

Prognosis Good (Relapses stop by 2nd Variable progression to renal
decade) damage
PATHO-
PHYSIOLOGY  2 Opposing theories, the underfill hypothesis and overfill
(2 SCHOOL OF hypothesis have been proposed as mechanism of Nephrotic
Edema
THOUGHTS)
 Massive Proteinuria

Hypoalbuminemia
Beta - LipoProteins

Decreased Plasma Oncotic Pressure

Hyper
Cholesterolemia

UNDERFILL Interstitial edema

HYPOTHESIS
Hypovolumia Increased
Increased RAAS ADH

Enhances
Na – H2O Retention
 Primary sodium retention (due to epithelial sodium channel in distal

tubule)

OVERFILL Volume expansion

HYPOTHESIS
Leakage of excess fluid into interstitium
• This explains the clinical picture of some patients with oedema
presenting with intravascular volume overload with HT
 Obscure
1. Derangement of cell mediated immunity
which alters the perm selectivity of the
PATHO- glomerular filter – Proteinuria
GENESIS 2. T helper 2 cells polarization
3. Derangement in T regulatory / T helper 17
axis.
 • Onset – Insidious
• Excessive weight gain due to-
Edema – peri-orbital initially , then in extremities , increases in the
morning , soft & pitting,
(Non pitting in Filariasis due to lymphatic obstruction)
CLINICAL hydrothorax ,ascites , scrotal oedema [hydrocoele] /labial swelling
FEATURES may be present.
Bloated appearance is misleading, severe muscle wasting after loss
of edema.
• Urine changes-decreased volume ,frothy and pale
• Edema of intestinal mucosa may lead to anorexia (loss of
appetite), poor intestinal absorption , diarrhea ,abdominal pain.
 • Hematuria
• Dysuria
• Fatigue , lethargic, irritability.
• Blood pressure may be normal or slightly decreased due to
CLINICAL decreased intravascular volume , might be increased/sustained ( in
FEATURES significant glomerular lesion)
• Fever may be present at the onset/ relapses.
• Dyspnea may be seen due to pleural effusion , huge ascites ,
pneumonia and other type of fluid.
FFA
PERIORBITAL
EDEMA
  Decreased micturition volume and frequency
 Rashes, Pyoderma, Sore Throat, Fever ,cough
 Joint pain ,bony pain

Present /Past  Abdominal pain, Diarrhea , Vomiting, Jaundice, blood in vomitus or

stool
History  Drug History, Insect bite, Allergies
 Headache, Blurring of vision ,Seizures, Altered sensorium
 Blood in urine, Burning Micturition, C0la coloured urine
• Breathlessness on exertion, Palpitations, chest pain ,cyanosis

Family History • Nephrotic syndrome

• Asthma and Allergies
• Renal diseases
• Tuberculosis
• Diabetes, Obesity,HT
  Protein losing enteropathy –H/O frequent diarrhoea
 Hepatic failure –Portal Hypertension {Triad
Jaundice ,Oesophageal Varices (Hemetemesis), Splenomegaly,
Superficial veins prominent}
 Heart failure- H/O Breathlessness, Palpitations, Cyanosis,
DIFFERENTIAL Tachycardia, feed intolerance, chest pain
DIAGNOSIS  Acute/Chronic Glomerulonephritis –HT, Cola coloured
urine ,H/O sore throat ,pyoderma
 Protein Malnutrition (Kwashiorkor)age 6 moths to 59 moths
 Severe Anaemia
 Hypothyroidism
  Urinalysis –EARLY MORNING /FIRST
 Proteinuria- 3+ to 4+
{Trace (10-30mg/dl); 1+ (30-100 mg /dl); 2+ (100-300 mg/dl)
3+(300-1000 mg /dl), 4+(more than 1gm/dl)}
 Gross hematuria ,straw colour ,frothy, cola coloured,occ microscopic
hematuria not uncommon

ESSENTIAL LAB  Persistent Microscopic Hematuria (>5 red cells/hpf ,urine

centrifuged @400gm for 4-5 mins , on 3 or more occasions)-significant
INVESTIGATION lesion(PSGN ,SLE,HSP, C3GLOMERULOPATHY)

@ Onset  Hyaline/Granular/Red Cell casts

 Spot Urine Protein/Creatinine ratio > 2.0
Urinary Protein Excretion > 40 mg/m2/hr or > 1gm/m2/day
 If more than 5pus cells /hpf then can suspect UTI
URINE Culture & Sensitivity
 BLOOD INVESTIGATIONS –
Serum Creatinine – normal or elevated
Blood Urea – Normal / Elevated in hypovolemia/severe dehydration , fall
in renal perfusion, severe edema , >72 hrs of diuretic therapy ,oliguria/anuria
 Serum Albumin - < 2.5 gm/dl (<3 gm/dl as per ISPN 2021) /
Serum Total Proteins
 Serum Cholesterol – elevated (>200 mg/dl)
 Serum Electrolytes levels (1.severe edema 2. >72 hrs of diuretic
therapy 3. dehydration/hypovolemia 4.oliguria/anuria)

 CBC ( for suspected systemic infection/hypovolemia)

 GBP, CRP ,ESR
 BLOOD CULTURE & SENSITIVITY
 Tuberculin Test ( Montoux Test)-TB causes NS and rule out TB,
can be activated /fulminant by steroids.
 Viral Markers- HIV 1 and 2, HbsAg, Anti HCV
  Chest Radiography
 if Positive Mantoux test
 history of contact
Additional  suspected LRTI

Evaluation  Renal USG

 if Plan for Kidney Biopsy
at  Gross Hematuria
Onset/Relapse  Renal Vein Thrombosis
 In severe hyp0v0lemia- Decreased IVC diameter and Increased
Collapsibility Index(110)
 Suspicion of CAKUT
  Complement C3 /C4/ Anti Nuclear Antibody / ASO titer–
 Gross Hematuria
 Persistent Microscopic Hematuria
 Sustained Hypertension

Additional Suspected Secondary Causes ( SLE/IgA Vasculitis/ C3
Glomerulopathy)
Tests  To Exclude Poststreptococcal Glomerulonephritis
 Liver Function Test –
 Serum Transaminases
 History of Jaundice / Liver Disease
 Serum Total IgG and IgM Levels
 1. Age below 12 months (genetic/congenital causes)& >16 yrs >12
years with persistent microscopic hematuria, low C3 & steroid
resistant.
2. Gross or persistent microscopic hematuria
3. Low blood C3
INDICATION 4. Persistent Hypertension
FOR KIDNEY 5. Impaired renal Function

BIOPSY 6. Failure of steroid therapy (Steroid Resistance)

7. Before starting Calcineurin Inhibitors (Cyclosporine A &
Tacrolimus) ,also after prolonged therapy(>30-36 months) &
Reduced Kidney function with decline in Estimated GFR that
persists after reduction in CNI doses.
8. Fever, Rash & Arthralgia(Systemic symptoms)
9. Acute Kidney injury not related to Hypovolemia
Minimal Change Disease
  Height/Weight/BMI for Malnutrition (in assessment for edema –Daily
weight recording from same weighing machine& bysame person)
 Vitals (Temperature, PR, HR, CRT, RR, BP)
 Abdominal girth if ascitis
 Salt moderation

MANAGEMENT  High protein diet (130-140 % of RDA) – 1.5-2 gm /kg/day in small

children
OF 1st EPISODE  Low Fat (Saturated)
NEPHROTIC  Treatment of infections/ INH prophylaxis for 6 months if

SYNDROME- Tuberculin test (Mantoux Test)positive with history of contact

Supportive  Parent Education –

explain about the disease & usual outcome
Taught to examine protein in urine (by dipstick/boiling test
with acetic acid excludes froth or coagulum due to inorganic
phosphates)2-3 days per week in remission/ per day if
infection or edema.
During remission , no dietary restriction needed
 vaccination
MANAGEMENT
OF EDEMA

IV albumin 5% or 20%
  Fluid Overload If Renal
Side Effects of Dysfunction
IV Albumin  Pulmonary Edema
Specific treatment ---
Corticosteroid therapy with Prednisolone or
prednisone – ( 2mg/kg per day or 60 mg/m2/day for 6 weeks followed by 1.5
mg/kg /40mg/m2single morning dose on alternate days for 6 weeks ) not on empty
stomach , BD or OD dosing
Remission occurs usually 10-14 days after starting therapy.

Steroid Sensitive (SSNS)

Body
Surface Area 1. >90% Minimal Change
2. 50% Mesangioproliferative
Calculation 3. 30% FSGS
 Definitions of Disease Course & Severity in Nephrotic Syndrome
Nephrotic Range Urine protein 3+ or 4+; urine protein to creatinine ratio (Up/Uc) >2 mg/mg in
Proteinuria first morning urine sample; proteinuria >40 mg/m2/h , 1 gm/m2/day

Remission Urine protein nil or trace (Up/Uc <0.2 mg/mg) for 3 consecutive early morning
specimens

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 or
(50% cases) during initial therapy ; ≥3 relapses in any 6-months; or ≥4 relapses in one yr
1
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
(3-10% cases) of 2 mg/kg (or 60 mg/m2) daily for 6 weeks

Complicated Relapse associated with life-threatening complications:

Relapse (i) hypovolemia requiring inpatient care
(ii) severe infection (peritonitis, cellulitis, meningitis)
(iii) Thrombosis
Significant Steroid Hyperglycemia (fasting glucose >100mg/dl, post prandial glucose >140
Toxicity mg/dL, or HbA1c >5.7%)
Obesity (body mass index >95th percentile ) Cushingoid features
Short stature (height <-2 SDS for
age) with height velocity (<-3 SDS for age)
Raised Intraocular pressure; cataract(s)
Myopathy ,Osteoporosis ,Osteonecrosis; or psychosis
Hypertension

Difficult to Treat Steroid Both of the following: (i) frequent relapses, or significant steroid toxicity
Sensitive Disease with infrequent relapses; and (ii) failure of ≥2 steroid sparing agents
(including levamisole, cyclophosphamide, mycophenolate mofetil)
  Parent Education
 Symptomatic therapy for infections in case of low grade
MANAGEMENT proteinuria (1+ - 2+)
 If Persistent high grade proteinuria ( 3+ - 4+ ) – –
OF Prednisolone ( 2mg/kg/day or 60 mg/m2/day until
INFREQUENT protein is negative/trace for 3 consecutive days )
RELAPSE  Followed by 1.5 mg/kg or 40 mg/m2 on alternate
days for 4 weeks )
 Treatment lasts for 5-6 weeks.
 Features of Hypovolemia during Relapse of Nephrotic Syndrome

Clinical Features
Abdominal Pain , Vomiting , Lethargy
Prolonged CFT , Cold Extremities
Tachycardia , Low volume Pulse
Low Blood pressure, Postural Hypotension

Biochemical Indices
Elevated Hematocrit
Fractional excretion of Sodium <0.5%
Urinary Potassium index (Urine K+/Urine Na+K) > 0.6
Ultrasonography – Decreased Inferior vena cava diameter , Increased Collapsibility index (110)
 Frequently relapsing, steroid dependent nephrotic syndrome

Prednisolone – 2mg/kg/day till remission , (0.5-0.7 mg/kg on alternate days

for 6-12 months ; daily 5-7 days during minor infections
MANAGEMENT Frequent relapses; steroid toxicity
OF Steroid threshold >1 mg/kg alternate

FREQUENT days
>1 complicated relapse
RELAPSES  No
Significant steroid toxicity
Yes Mycophenolate mofetil(high
Frequent dose
Levamisole Relapses Cyclophosphamide
Mycophenolate mofetil Difficult - to-Treat
(low dose) Disease
Cyclosporine, tacrolimus

Rituximab
Medication Dose Duration Adverse Effects Recommended Monitoring
Prednisolone 0.5-0.7 mg/kg on 6-12 Cushingoid features; Short stature hypertension hypertension
alternate day months raised intraocular pressure Anthropometry q 3-6 mo;
Glucose intolerance cataract ,elevated eye evaluation q 6-12 month; blood
Transaminases sugar and transaminases q 3-6 month

Levamisole 2-2.5 mg/kg on 2-3 years Leukopenia, ANCA positive vasculitis, high Blood counts q 2-3 month;
Alternate day transaminases, Seizures transaminases q 4-6 month
Cyclo-Phosphamide 2-2.5 mg/kg/day 8-12 week Leukopenia, alopecia, infections; discolored nails; Blood counts q 2 weeks
orally hemorrhagic cystitis; gonadal toxicity and Maintain hydration; discontinue during
malignancies significant infections Co-administer with
prednisolone 1 mg/kg AD

Mycophenolate 600-1200 2-3 Abdominal pain, diarrhea, nausea, weight loss; Screen for adverse effects
Mofetil mg/m2/day in years viral warts; Blood counts and
divided doses; AUC leukopenia; elevated transaminases transaminases q 3-6 mo
>45 mg·h/L
Cyclosporine 4-5 mg/kg/day 2-3 Both: Nephrotoxicity, hyperkalemia, Screen for cosmetic side
in divided doses; years hepatotoxicity effects, tremors, diarrhea,
trough 80-120 Cyclosporine: Gingival hyperplasia, hypertrichosis; hypertension
ng/mL hypertension; dyslipidemia,6H Creatinine, potassium at 2-4 weeks, q 3-
Tacrolimus: Tremors, seizures, headache; diarrhea; 6 mo
Tacrolimus 0.1-0.2mg/kg/d in 2-3 glucose intolerance; hypomagnesemia Liver function tests, glucose, uric acid,
divided doses; years magnesium and lipids q 3-6 mo
trough 4-8 ng/mL
Rituximab 375 mg/m2, slow IV 2 doses, Chills, fever; serum sickness; bronchospasm ,Acute lung Pre dose: Blood counts,
infusion 1-week injury ,Neutropenia;P. jirovecii pneumonia; reactivation of transaminases; hepatitis
apart hepatitis B or JC virus; Hypogammaglobulinemia and HIV serology; immunoglobulin G (IgG) level
Post therapy: CD19 counts; blood counts; IgG;
consider cotrimoxazole prophylaxis
 Cyclophosphamide is avoided in Children (<5-7
year old) due to reduced efficacy & in Peri-
Pubertal Boys due to Risk of Gonadal Toxicity.

 Rituximab is avoided in Young Children due to

risk of Hypogammaglobulinemia.
 1) Edema (fluid overload & pulmonary edema)
2) Infections –
• Varicella
• St pneumoniae
• Gram –ve organisms may presents as -
• Peritonitis( low grade fever, diarrhoea, abdominal discomfort)
• Cellulitis
COMPLICATION • Pneumonia

S • Meningitis
• Sepsis
Rx -Antibiotics , Acyclovir, Vaccines when off steroid for 4 weeks
3) Thrombotic complications – Cerebral , Pulmonary , Renal vein
thrombosis.
 Rx-LMWH & Oral anticoagulants.
 Aggressive use of diuretics, Venipuncture of deep veins (brachial,
femoral), Hypovolemia
4)Hypovolemia and Acute renal Failure
5)Steroid Toxicity
 Management of Serious Infections
Infections Organism Diagnosis Treatment
Peritonitis S.Pneumoniae Ascitic fluid >100 cells/mm3 Ceftriaxone or Cefotaxime for 7-10
S.Pyogenes >50% neutrophils days
E.Coli Ascitic fluid – Culture , Latex Ampicillin and
Gram –ve bacteria agglutination, PCR Gentamicin/Amikacin for 7-10 d

Pneumonia S, Pneumoniae , S.aureus Chest Xray, Blood culture, Sputum Oral- Amoxicillin, Coamoxiclav,
H.Influenzae , for gram stain & culture cefuroxime * 10-14 days
IV Ceftriaxone & Amikacin *7-10d
H1N1 influenza Throat swab for H1N1 Oseltamivir for 5 days
M.tuberculosis Tuberculin test, pleural tap, Therapy as per NTEP
gastric aspirate, Sputum CBNAAT

Cellulitis S.Aureus , S.pyogenes Pus for culture, Sensitivity , Blood IV Coamoxiclav , Cloxacillin with
H. Influnzae culture Ceftriaxone * 7-10 days
Gram –ve bacteria
Sepsis S.Pneumoniae , Gram –ve CBC , CRP Ceftriaxone & Amikacin * 10-14 days
bacteria Procalcitonin , Blood culture

Varicella Varicella zoster virus Clinical IV acyclovir (1500 mg/m2/day in

three doses) or oral Acyclovir (80
mg/kg/day in four doses) * 7-10 d
  Diagnosis – Lack of complete remission despite therapy with daily
STEROID – prednisolone at a dose of 2 mg/kg (or 60 mg/m2) daily for 6 weeks
 Indication for renal biopsy
RESISTANT  Etiology – 20-30% - Genetic/Sporadic (homozygous / compound
NEPHROTIC heterozygous mutations in genes)
 Encoding Podocyte proteins Podocin (NPHS2) , Nephrin
SYNDROME (NPHS1) , Wilms Tumor (WT1) , other >70 genes mutations
also present.
 • Indications for mutational analysis :
Congenital Nephrotic Syndrome
Family History of SRNS
Sporadic resistance to steroids
Girls with steroid resistant FSGS
STEROID –
• Management-
RESISTANT  Steroids + Calcineurin inhibitors + ACE inhibitors / ARBs’ +
NEPHROTIC HMG coenzyme-A + Diuretics
ACE inhibitor – Enalapril- 0.3-0.6 mg/kg/day /Ramipril –
SYNDROME 6mg/m2/day
 Role- Decrease in Proteinuria & Control of hypertension
 Side effect – 1.Dry Cough
 2. Hyperkalemia
 3.Decline in Renal Function
  Angiotensin Receptor Blockers – Losartan / Valsartan
 Indication – Persistent dry cough due to ACE
inhibitors
STEROID –  Add on therapy for better Anti Proteinuric effect
RESISTANT
NEPHROTIC  HMG Coenzyme A Reductase inhibitors – used in
SYNDROME Persistent Hypercholesterolemia
  Presents in first 3 months of life
 Anasarca, hypoalbuminaemia, oliguria
1)‘Finnish’ Type Nephrotic Syndrome- Autosomal
recessive – NPHS 1 - Nephrin
 Antenatally detectable
CONGENITAL  Raised AFP in maternal serum and amniotic fluid
NEPHROTIC  Renal Histology – At birth – Ultrastructural abnormality of
GBM
SYNDROME  After Few months of life – Microcystic dilatation of
proximal tubules
 Complications –
 Failure to thrive
 Recurrent Infections
 Hypothyroidism
 Renal Failure ( 2 – 3 yrs )
 2) Denys-Drash Syndrome- mutation in WT1 gene
 Presents as Male Psuedohermaphroditism
 High risk of Wilms Tumor (B/L)
 Progressive Renal failure
 Renal Histology – Diffuse mesangial sclerosis

CONGENITAL 3) Gallaway Mowat Syndromes – features of Nephrotic syndrome +

NEPHROTIC Developmental delay

SYNDROME  Other causes

 Intra Uterine infections eg Syphilis, CMV & Toxoplasmosis , Mutations in
PLCE1/NPHS2 genes(Podocin)
 Rx- Appropriate nutrition
- Control of oedema
- Thyroxin supplements
- Reduction of proteinuria by ACE inhibitors / Indomethacin
- Regular IV Albumin infusion every 2-3 weeks for marked
Hypoalbuminemia & oedema
 Principles of Immunization with Live Vaccines in Pateints with Nephrotic Syndrome
Immunosupression Advice
Receiving high dose prednisolone (>2mg/kg/d , >20 Vaccinate immediately after discontinuing
mg/day if >10 kg ) for <14 day treatment

Receing high dose prednisolone (>2mg/kg/d , >20 Vaccinate 1 month after discontinuing
mg/day if >10kg) for >14 days corticosteroids
Receiving low-moderate dose Prednisolone (<2 No live vaccines , until discontinuation of steroid
mg/kg/d or equivalent , <20 mg/d ) therapy
Low dose alternate day prednisolone and pressing Live vaccine may be administered
need for Vaccine
Pateints receiving Cyclophosphamide Avoid live vaccines until off therapy for 3 months

Patients receiving Calcineurin inhibitors , Avoid live vaccines until off therapy for 1 month
Levamisole or Mycophenolate mofetil
Therapy with Rituximab Avoid live vaccines until after B-cell recovery (6-9
months)
Immunocompetent siblings & household contacts Do not administer OPV , may receive MMR ,
Rotavirus & Varicella vaccine
Household contacts older than one year Administer influenza vaccine annually
 Specific Vaccines for Patients with Nephrotic Syndrome
Vaccine Age Previously received Vaccine Schedule
Pneumococcal 6-72 Completely immunized (3 PCV 13/10 One dose >2 year old
Conjugate (PCV , months doses at 6,10 & 14 weeks ,
13 valent booster at 12-15 months) PPSV23 One dose when >2 year old & >8
preferred to 10 week after last PCV 13/10 dose
valent) Incompletely immunized PCV 13/10 2 doses , >8 weeks apart
Polysaccharide
(23 valent , PPSV23 1 dose when >2 year old & >8
PPSV23) week after last PCV 13/10 dose
>6 years Completely immunized PPSV23 1 dose
Incompletely immunized PCV 10/13 1 dose
PPSV23 1 dose >8 weeks after last
PCV13/10 dose
Varicella >15 months No evidence of immunity Live 2 doses 4-8 weeks apart
Attenuated
Influenza >6 months Inactivated Anually
Hepatitis B Any No , or Anti-HBs Subunit 3 doses at 0,1 & 6 months, or in
<10mIU/mL (10 microG/0.5 accelerated schedule with >4
mL) week gap between doses 1 & 2 ,
>8 week between doses 2&3 , &
>16 week between dose 1 & 3
THANK YOU