SETH G.S. MEDICAL COLLEGE & K.E.M.
HOSPITAL
PAREL, MUMBAI - 12
APPROACH TO PROTEINURIA
& NEPHROTIC SYNDROME
SELF DIRECTED LEARNING SESSION (SEMINAR) - PAEDIATRICS
PAURAS MHATRE
Final Year MBBS Student, August 2020 Batch
Posted in Dr. RKV Unit
NEPHROTIC
SYNDROME
SLO’S
RELEVANT
4 Definition
COMPETENCIES Etiology
5
Student should be able to: 8 Terminologies
PE21.3 Discuss the approach and referral criteria to a child
with Proteinuria
PE21.8 Elicit, document and present a history pertaining to
9 Clinical Features
diseases of the Genitourinary Tract
PE21.9 Identify external markers for Kidney disease, like
16 Management
Failing to thrive, hypertension, pallor, ichthyosis, anasarca
PE21.10 Analyse symptom and interpret the physical findings
and arrive at appropriate provisional/ differential diagnosis 21 Complications
24 SRNS & Congenital Nephrotic Syndrome
DEFINITION
Nephrotic syndrome (NS) is a clinical syndrome defined by massive proteinuria
(greater than 1 g/m²/day or greater than 3 g/day) responsible for hypoalbuminemia
(less than 2.5 g/dL), with resulting hyperlipidemia, edema, and various complications.
04
ETIOLOGY
Nephrotic Syndrome is caused by increased permeability through the damaged
basement membrane in the renal glomerulus. It results from an abnormality of
glomerular permeability that may be primary with a disease-specific to the kidneys or
secondary to congenital infections, diabetes, systemic lupus erythematosus, neoplasia,
or certain drug use.
There are 3 chief varieties of Nephrotic Syndrome:
1. Congenital Nephrotic Syndrome
2. Primary or Idiopathic Nephrotic Syndrome
3. Secondary Nephrotic Syndrome
05
ETIOLOGY - PRIMARY OR IDIOPATHIC NS
Most Common Variety of Nephrotic
Syndrome in Childhood (>85% cases)
Histopathologic Types of Primary
Nephrotic Syndrome:
1. Minimal Change Nephrotic
Syndrome/Glomerulopathy
(MCNS/MCGP) - >75%
2. Focal Segmental
Glomerulosclerosis (FSGS) - 7 to
10%
3. Mesangioproliferative
Glomerulonephritis (MPGN) - 5 to
7% (Image Courtesy: Harsh Mohan’s Textbook of Pathology, 7th edition)
4. Membranous Nephropathy (MN) -
Rare
06
ETIOLOGY - SECONDARY NS
Causes of Secondary Nephrotic Syndrome
Post- Collagen Hematological Malignancy Endocrine Drugs Miscellaneous
Infectious Vascular Ds
Bacterial: SLE Sickle Cell Leukemia Diabetes Captopril Snake Venom
Group A Beta- Rheumatoid Disease Lymphoma Mellitus Fenoprofen Henoch-
hemolytic Arthritis Renal Vein Wilm’s tumour Gold Schonlein
streptococci Peri-arteritis Thrombosis Pheochromo- Lithium Purpura
Viral: nodosa cytoma Mercury Heroin
Varicella Probenecid Addiction
Hepatitis B Trimethadione
HIV Warfarin
Infectious Histopathologic Types seen in Secondary NS:
Mononucleosis 1. Mesangioproliferative Glomerulonephritis (MPGN) - 5 to 7%
Protozoal: 2. Membranous Nephropathy (MN) - 3 to 5% 07
Malaria
TERMINOLOGIES IN COURSE OF ILLNESS
Remission: Urine albumin nil or trace for three consecutive early morning specimens
Relapse: Urine albumin 3+ or 4+ (or proteinuria greater than 40 mg/m²/h) for three
consecutive early morning specimens, having been in remission previously
Frequent relapses: Two or more relapses in the initial six months or more than four
relapses in any 12 months
Steroid dependence: Two consecutive relapses when on alternate day steroids or
within 14 days of its discontinuation
Steroid resistance: Absence of remission despite therapy with daily prednisolone at
a dose of 2 mg/kg per day for four weeks
08
CLINICAL FEATURES - SYMPTOMS
EDEMA
Most common symptom and presenting
complaint
Insidious in onset
Bilaterally symmetrical
More in morning
First noticed around eyes (periorbital),
followed by legs
Soft and pitting in nature
Progresses to generalised edema
(anasarca) in severe cases
Severe edema associated with ascites,
hydrocele, hydrothorax 09
CLINICAL FEATURES - SYMPTOMS
URINARY:
Frothy urine
Rarely, oliguria
Hematuria - Rare in MCNS, could be seen in other types
TIREDNESS, LACK OF APPETITE
10
CLINICAL FEATURES - EXAMINATION
GENERAL EXAMINATION:
Hypertension +/-
Blood Pressure is usually normal.
Sustained elevation is sign of significant lesion/ advanced disease
Growth Retardationon anthropometry in cases of frequent relapsers/ steroids
Edema
Pallor?
Signs of infection +/-
11
CLINICAL FEATURES - EXAMINATION
PA EXAMINATION:
Ascites +/-
Hepatomegaly +/-
Ballotable Kidneys?
RS EXAMINATION:
Signs of Pleural Effusion +/-
CVS EXAMINATION:
Usually Normal
Signs of Pericardial Effusion +/- in advanced cases
CNS EXAMINATION
Usually Normal
Complications +/- in advanced cases
12
EVALUATION - INVESTIGATIONS
TO CONFIRM DIAGNOSIS:
CBC - Anemia, Leukocytosis +/-
ESR - Elevated
Urine Routine Analysis
Proteinuria > 3+
Hematuria +/-
Pyuria +/-
Casts - Fatty/ RBC
Sr. Albumin - < 2.5 g/dL
Sr. Cholesterol - Elevated
BUN and Sr. Creatinine - Normal in MCNS, Elevated +/- other types
13
EVALUATION - INVESTIGATIONS
TO RULE OUT INFECTIONS: SUPPLEMENTARY:
Blood Culture, if leukocytosis + USG Abdomen
Mantoux Test Renal Doppler
X-Ray Chest Ascitic Tap
Urine Culture
PSMP
HBsAg
VDRL
14
EVALUATION - INVESTIGATIONS
IN CASES OF ATYPICAL PRESENTATION/
FREQUENT RELAPSES/ SRNS:
To rule out nephritis
Sr. Complement Levels
ASLO
Throat Swab for culture & smear
Secondary NS is suspected:
ANA
dsDNA
RA Test
Frequent Relapses/ Steroid Resistance:
Kidney Biopsy
15
MANAGEMENT- INITIAL EPISODE
Very Important as this decides the long term course of disease
SYMPTOMATIC
High Protein Diet
Salt Restriction - No Extra Salt
Treatment of Associated Infections, Screening of Parents for Tuberculosis
Diuretics, if edema is significant - Should be used cautiously
Furosemide (1-4 mg/kg/day in 2 divided doses)
+/- Spironolactone (2-3 mg/kg/day in 2 divided doses)
16
MANAGEMENT- INITIAL EPISODE
DEFINITIVE
Steroids is the mainstay of treatment
Prednisolone or Prednisone
60 mg/m²/day (max. 60 mg) in single or divided doses for 6 weeks, followed by,
40 mg/m²/day (max. 40 mg) in single morning dose on alternate days for 6 weeks
Then therapy is stopped
Remission (abolition of proteinuria) usually by 10-12 days followed by diuresis and
loss of edema
Counselling of parents for completion of therapy is important
17
MANAGEMENT- RELAPSE
Relapses are often trigerred by minor infections
Low grade (1-2+) Proteinuria: Treatment of infection will cause remission
High grade (3-4+) Proteinuria: Requires definitive treatment
Prednisolone or Prednisone is the mainstay
60 mg/m²/day in single or divided doses until urine protein negative or trace,
followed by,
40 mg/m²/day in single morning dose on alternate days for 4 weeks
Then therapy is stopped
First 2-3 relapses treated as above, after which relapse pattern is known and
therapy is individualised accordingly. Infrequent relapsers treated like above SOS.
18
MANAGEMENT- FREQUENT RELAPSES & SDNS
Drug Dose Duration Adverse Effects
0.3-0.7 mg/kg on Cushingoid body habitus, hypertension, short stature,
Prednisolone 9-18 months
alternate days cataract, hirsutism
2.0-2.5 mg/kg on
Levamisole 1-2 years Leukopenia, rash, flu-like symptoms
alternate days
Leukopenia; alopecia; gonadal toxicity; nail discoloration.
Cyclophosphamid
2.0-2.5 mg/kg/day 12 weeks (Hemorrhagic cystitis; nausea and vomiting are more
e
common with IV administration)
19
MANAGEMENT- FREQUENT RELAPSES & SDNS
Drug Dose Duration Adverse Effects
20-25 mg/kg/day
Mycophenolate
or 600-1000 1-3 years Gastrointestinal discomfort, diarrhea; leukopenia
Mofetil
mg/m²/day
Acute and chronic nephrotoxicity, elevated
Cyclosporine CsA: 4-5 mg/kg/d transaminases (both agents); hirsutism, gum hyperplasia,
12-36
(CsA) Tac: 0.1-0.2 hypertension or hyperlipidemia (CsA > Tac);
months
Tacrolimus (Tac) mg/kg/d hyperglycemia, neurotoxicity with headache and seizures
(Tac > CsA)
375 mg/m² IV Infusion reactions (fever, rash, bronchospasm);
Rituximab 1-2 doses
once per week neutropenia
20
COMPLICATIONS
Edema:
Salt Restriction (Usual amounts in food)
Oral Furosemide +/- Spironolactone
Albumin Infusion for severe hypoalbuminemia causing poor renal perfusion &
oliguria
Infections:
Common organisms: S. pneumoniae, gram negative organisms, Varicella
Severe infections like peritonitis, cellulitis, pneumonia, meningitis
Varicella treated with oral acyclovir x 7 days, IV in severe
Immunization with pneumococcal and varicella vaccines once patient is off
steroid for 4 weeks
21
COMPLICATIONS
Thrombotic:
Renal, Cerebral and Pulmonary veins
Risk Factors: Aggresive use of Diuretics, Frequent puncture of deep veins,
Hypovolemia
Treatment: Low Molecular Weight Heparin followed by Oral Anticoagulants
Albumin Infusion for severe hypoalbuminemia causing poor renal perfusion &
oliguria
Steroid Toxicity:
Features: Cushingoid features, short stature, hypertension, osteoporosis,
subcapsular cataract
Withdraw/reduce dose and start steroid sparing agents
22
COMPLICATIONS
Hypovolemia and Acute Renal Failure:
Features: Abdominal Pain, Lethargy, Dizziness, Leg cramps,Tachycardia,
Hypotension, Delayed CRT, Low Volume Pulses, Clammy distal extremities
Investigation Findings: ↑ Blood Urea:Creatinine Ratio; High Hematocrit, Urine
Sodium <20 mEq/L, 0.2-0.4% Fractional excretion of sodium, Urinary potassium
index [(urine K+)/(Urine K+ + Urine Na+)]> 0.6
Discontinue Diuretics
Rapid Infusion of Saline (10-20 mL/kg) over 20-30 min
If NR, 5% Albumin (10-15 mL/kg) or 20% Albumin (0.5-1.0 g/kg)
23
STEROID RESISTANT NS (SRNS)
DEFINITION/ DIAGNOSTIC CRITERIA:
Lack of remission despite treatment with prednisolone, at a dose of 2 mg/kg/day (60
mg/m²/day) for 4 weeks followed by 1.5 mg/kg (40 mg/m²/day) on alternate days for
another 4 weeks. Exclusion of systemic infections causing persistent proteinuria is
essential.
INVESTIGATIONS:
Baseline Assessment: Renal Function, Blood levels of Albumin and Cholesterol,
Estimation of Proteinuria
Evaluation for secondary causes
Children should undergo renal biopsy before instituting specific treatment
24
MANAGEMENT - STEROID RESISTANT NS
Patients with SRNS secondary to MCNS, FSGS and MPGN are treated similarly.
Chief factor predicting outcome is response of proteinuria to therapy rather than
histopathologic type.
DEFINITIVE TREATMENT
Drug options are:
Calcineurin Inhibitors - Cyclosporine or Tacrolimus
Cyclophoshamide - IV (pulses) or Oral
High Dose Corticosteroids with Cyclophosphamide - MPS (in pulses) with
Prednisolone (in tapering doses)
25
MANAGEMENT - STEROID RESISTANT NS
ADJUNCTIVE TREATMENT
ACE Inhibitors for control of proteinuria and hypertension
ARB’s if dry cough as ADR of ACEI’s, or as on add-on (?Better antiproteinuric effect)
HMG-CoA reductase inhibitors for persistent hypercholesterolemia
Management of infections with appropriate antibiotic/antiviral therapy
Diuretics judiciously for edema
Albumin infusion for hypovolemia, with close monitoring to avoid fluid overload and
pulmonary edema
26
CONGENITAL NEPHROTIC SYNDROME
Presents in first 3 months of life with anasarca,
hypoalbuminemia, oliguria
Etiology is heterogenous. Examples:
Finnish form: NPHS1 gene mutation, AR inheritance
Denys Drash Syndrome: WT1 gene mutation - Congenital
NS, Male Pseudohermaphroditism, Wilms Tumour
Management:
Appropriate Nutrition
Control of Edema
Thyroxin Supplements
Control of Proteinuria: ACEI’s and/or Indomethacin
Regular use of IV albumin infusions: Mx of anasarca,
Prophylactically 27
(Vinod K Paul, Arvind Bagga. Ghai Essential Pediatrics. CBS Publishers and
Distributors.
BIBLIOGRAPHY & REFERENCES
Aruchamy Lakshmanaswamy. Clinical Paediatrics. Jaypee Brothers Publishers.
Mayoor K. Chheda. Practical Aspects of Pediatrics. CBS Publishers and
Distributors.
Tapia C, Bashir K. Nephrotic Syndrome. [Updated 2022 Jun 5]. In: StatPearls
[Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan.
Eddy AA, Symons JM. Nephrotic syndrome in childhood. Lancet. 2003 Aug
23;362(9384):629-39. doi: 10.1016/S0140-6736(03)14184-0. PMID: 12944064.
Kumar, Abbas, Aster. Robbins & Cotran Pathologic Basis of Disease. Elsevier, Inc.
Harsh Mohan. Textbook of Pathology. Jaypee Brothers Publishers.
Medical Council of India. Competency based Undergraduate curriculum for the
Indian Medical Graduate, 2018. Vol. 2.
Maharashtra University of Health Sciences. Third MBBS Paediatric Syllabus.
28
THANK
YOU
