This document provides an overview of nephrotic syndrome in children. It defines nephrotic syndrome as a glomerular disease characterized by heavy proteinuria, hypoalbuminemia, edema, and hyperlipidemia. The document discusses the epidemiology, etiology, pathophysiology, clinical features, investigations, treatment, complications, and prognosis of nephrotic syndrome. It notes that the majority of nephrotic syndrome cases in children are primary or idiopathic in nature and often steroid-responsive. The long-form document provides detailed information on different types of nephrotic syndrome and their clinical management.

1. BY
DR. EKE EGHOSASERE PAUL
DEPT. OF PAEDIATRICS
FEDERAL MEDICAL CENTRE, KEFFI, NASARAWA
STATE

2. OUTLINE
 Introduction/Definition
 Epidemiology
 Aetiology
 Pathophysiology
 Clinical Features
 Investigations
 Differentials
 Treatment
 Complications
 Prevention
 Prognosis
 Conclusion
 References 2

3. INTRODUCTION
 Nephrotic Syndrome (NS) has been described by
physicians as far back as the 17th century
 Theodore Zwinger III of Basel (1658-1724) described
the oedema of NS at length
 Domenuco Cotugno (1736-1820) in Naples described
the proteinuria associated with the oedema
 Leiter first introduced the term “Nephrotic Syndrome”
in 1931
3

4. INTRODUCTION Contd.
 Nephrotic Syndrome (NS) is primarily a paediatric
disorder
 It is the most common chronic renal disease of
childhood
 Long term and day-to-day management of a child with
NS should be a collaboratory effort between the
primary care physician and paediatric nephrologist
4

5. DEFINITION
Nephrotic Syndrome (NS) is a manifestation of
glomerular disease characterized by
 Heavy proteinuria > 3.5g/day or > 40mg/m2/hr or 3+ or
4+ (albustix) or early morning spot urine
Protein:Creatinine of > 2-3:1
 Hypoalbuminaemia < 2.5g/dL
 Massive generalized oedema
 Hyperlipidaemia: cholesterol level > 250mg/dL or >
6mMol/L
5

6. EPIDEMIOLOGY
 Among Caucasians, idiopathic NS constitutes about
90% of their cases, with minimal change disease being
responsible for 85% of these
 In Africa, membranoproliferative and focal segmental
glormerulosclerosis (FSGS) are common
 FSGS is currently the most common glomerular
disorder resulting in end stage kidney disease in
children and young adults in US and many parts of the
world
6

7. EPIDEMIOLOGY Contd.
 31% of 2266 Nigerian children treated for renal disease
were found to have Nephrotic Syndrome (Okoro and
Okafor, 1998)
 Incidence: 2-4 new cases/100,000 population per year
 Peak age incidence in most Nigerian centres occurs in
the school age as against pre-school age reported in
Caucasian series
 Commoner in males, M:F = 2:1
7

8. AETIOLOGY
There are 3 varieties of Nephrotic Syndrome:
 Primary (Idiopathic) Nephrotic Syndrome
 Secondary Nephrotic Syndrome
 Congenital Nephrotic Syndrome
8

9. A. PRIMARY NEPHROTIC SYNDROME
 Minimal change nephrotic syndrome
 Focal segmental glomerulosclerosis
 Membranoproliferative glomerulonephritis
 Membranous Nephropathy
9

10. MINIMAL CHANGE NEPHROTIC
SYNDROME (MCNS)
 Most common histologic form of primary NS in children
 More than 80% of children under 7 years of age with NS
have MCNS
 Children 7 to 16 years old with NS have a 50% chance of
having MCNS
 M:F = 2:1
 Response to steroids= 90%
10

11. FOCAL SEGMENTAL
GLOMERULOSCLEROSIS (FSGS)
 Accounts for approximately 10-20% of children with primary
NS
 May present like MCNS, or with less impressive proteinuria
 FSGS may develop from MCNS or present as a separate entity
 A circulating factor that increases glomerular permeability is
found in some patients with FSGS
 Over 1/3 of children with FSGS progress to renal failure
 Response to steroids: 15-20%
11

12. MEMBRANOPROLIFERATIVE
GLOMERULONEPHRITIS (MPGN)
 Characterized by hypocomplementaemia with signs of
glomerular renal disease
 Present in 5-15% of children with primary NS
 Typically persistent
 Has a high likelihood of progression to renal failure over
time
 Response to steroids: not established
12

13. MEMBRANOUS NEPHROPATHY
 Occurs in less than 5% of children with primary NS
 Seen most commonly in adolescents and children with
systemic infections like hepatitis B, syphilis, malaria
and toxoplasmosis
 Also seen in those receiving drug therapy (gold salts,
penicillamine)
 Response to steroids: may be slow progression
13

14. B. SECONDARY NEPHROTIC
SYNDROME
1. Post infectious:
a. Protozoal:
Plasmodium malariae: very important here, in late 1960’s
said to have accounted for 80% of patients with NS in
Ibadan, ¼ of cases seen in Zaria
P. falciparum: rarely
Toxoplasmosis
b. Bacterial: post streptococcal AGN, syphillis (rarely)
c. Viral: HBV, CMV, Varicella, HIV
d. Parasitic: S. mansoni (sometimes haematobium), filariasis
14

15. SECONDARY NS Contd.
2. Multisytemic and connective tissue diseases: SLE, Henoch
Schonlein purpura, Sarcoidosis, Amyloidosis
3. Allergic disorders: bee sting, serum sickness, poison ivy,
pollens
4. Drugs and heavy metals: mercury, lead, gold,
penicillamine, trimethadione
5. Neoplastic: lymphomas, leukaemias, Wilms tumour
15

16. SECONDARY NS Contd.
6. Heredo-familial disorders: SCD, Alport syndrome,
Wegener vasculitides
7. Metabolic: Diabetes mellitus, hypothyroidism
8. Transplant rejection
16

17. C. CONGENITAL NEPHROTIC
SYNDROME
 Presents during the 1st 2 months of life, 2 common types
 The Finnish type: autosomal recessive, more common in
persons of Scandinavian descent, due to a mutation in
the nephrin protein component in the glomerular
filtration slit
 Second type: heterogenous group of abnormalities
including diffuse mesangial sclerosis and conditions
associated with drugs or infections; prenatal onset is
supported by elevated levels of maternal alpha-
fetoprotein 17

18. PATHOPHYSIOLOGY
 Underlying abnormality: increased permeability of
glomerular capillary wall
 On biopsy: extensive effacement of podocyte foot
processes, normal negative charge which restricts filtration
of serum proteins is lost
 Idiopathic NS: Complex disturbances in T-cell mediated
immunity
 FSGS: mutations in podocyte proteins (podocin, α-actinin
4) and MYH9 (podocyte gene)
 Steroid resistant NS: mutations in NPHS2 (podocin) and WT1
genes
18

19. 19

20. 20

21. PATHOPHYSIOLOGY Contd.
 Massive proteinuria results in decline of serum
proteins (albumin)
 Reduced plasma oncotic pressure leads to fluid shift
from vascular to interstitial compartment, and plasma
volume contraction
 Oedema enhanced by activation of renin-angiotensin-
aldosterone system
 Liver lipoprotein synthesis is increased, leading to
elevated serum lipids (cholesterol, triglycerides)
21

22. CLINICAL FEATURES
1. Oedema:
 Usually starts from the face (periorbital swelling),
limbs, abdomen, genitalia
 Subsides with ambulation
 Weight increase in spite of poor appetite
 Patients present late (sometimes about 1-2 months)
after onset of symptoms
22

23. CLINICAL FEATURES Contd.
2. Abdominal swelling, abdominal pain
3. Diarrhoea
4. Anorexia
5. Frothy urine,  decreased urinary output
6. Change in quality of hair: related to protein deficiency
23

24. CLINICAL FEATURES Contd.
7. Pallor and shiny skin
8. Ascites
9. Blood Pressure: usually normal in early stage, could be
raised in MPGN
10. Respiratory difficulty from pleural effusion
11. Features of infection: pneumonia, UTI
24

25. INVESTIGATIONS
1. Urinalysis:
 Dip stick: 3+ or 4+ proteinuria
 Microscopic haematuria (20% of children)
Other tests of proteinuria:
 24 hour urinary protein excretion = >2g/day
 Spot urine Protein : Creatinine > 2-3: 1
2. Urine microscopy: RBC, WBC casts 25

26. INVESTIGATIONS Contd.
3. Serum electrolytes, urea and creatinine:
 Na+ normal/low
 Ionized Ca2+ normal, total Ca2+ reduced
 Creatinine: normal/increased
 Cl-, K+, HCO3
-, urea: usually normal
4. Serum albumin ↓, < 2.5g/dL
5. Cholesterol ↑, > 250mg/dL
6. Stool: S. mansoni ova
7. Others: FBC, Hepatitis B and C testing, HIV, serum
complement
26

27. INVESTIGATIONS Contd.
8. Renal biopsy; indications include:
 Age of onset < 1 year or > 8 years
 Steroid resistance
 Frequent relapses or steroid dependency
 Significant chronic nephritic manifestations:
haematuria, hypertension, renal insufficiency,
hypocomplementaemia
27

28. DIFFERENTIALS OF NEPHROTIC
SYNDROME
 Acute glomerulonephritis
 PEM (Kwashiokor)
 CCF (Right heart failure)
 Chronic liver disease
 Beri-Beri
28

29. TREATMENT
 1st episode of NS with mild/moderate oedema may be
managed as outpatients
Indications for admission:
 Generalized oedema severe enough to cause respiratory
distress
 Tense scrotal or labial oedema
 Complications: sepsis, peritonitis, pneumonia,
thromboembolic phenomenon, FTT
 Patient or family compliance with treatment is in doubt
29

30. TREATMENT Contd.
 Children 1-8 years with uncomplicated NS most likely
steroid responsive, steroids can be commenced
without renal biopsy
 Prednisone 2mg/kg/day (60mg/m2/day, maximum
60mg/day), divided into two to four doses per day for
4-6 weeks
 Then, tapered down to 40mg/m2/day given every other
day as a single daily dose for at least 4 weeks
30

31. TREATMENT Contd.
 Remission: diuresis, urine trace or negative for protein for 3
consecutive days
 Relapse: 3-4+ proteinuria plus oedema; prednisone
60mg/m2/day in a single AM dose until remission, then
switched to alternate day dosing, tapered over 4-8weeks
 Steroid dependent: relapse while on alternate day steroid
therapy, or within 28 days of completing therapy
 Frequent relapsers: respond well to prednisone therapy but
relapse > 4 times in a 12 month period
 Steroid resistant: proteinuria (2+ or greater) after 8 weeks
of steroid therapy 31

32. TREATMENT Contd.
 For steroid resistant NS: cyclophosphamide (2mg/kg over
8-12 weeks), chlorambucil, cyclosporine A, levamisole
 Oedema:
 Restriction of salt intake
 Loop diuretics eg. Frusemide, with spironolactone
 If severe: cautious administration of 25% albumin (0.5-
1.0g/kg IV over 1-2 hours) with an IV loop diuretic
 Albumin is rapidly excreted, salt restriction and diuretics
should be continued
32

33. TREATMENT Contd.
 Acute hypertension is treated with β-blockers or
calcium channel blockers
 Persistent hypertension usually responds to angiotensin-
converting enzyme (ACE) inhibitors
 ACE inhibitors and angiotensin II blockers also helpful as
adjunct therapy to reduce proteinuria in steroid-resistant
patients
33

34. TREATMENT ALGORITHM FOR NS
34

35. COMPLICATIONS
1. Increased susceptibility to infections (peritonitis: S.
pneumoniae, E. coli, Klebsiella)
 Reduced immunoglobulins
 Oedema fluid acting as a culture medium
 Reduced bactericidal activity of leococytes
 Immunosuppressive therapy
 Reduced perfusion of the spleen due to hypovolaemia
 Loss in urine of factor B (alternative pathway
particularly significant in opsonization of
encapsulated organisms)
35

36. COMPLICATIONS Contd.
2. Hypovolaemia: diarrhoea, diuretics
3. Hypercoagulative state, thromboembolism: increased
prothrombotic factors (fibrinogen) and loss of
fibrinolytic factors (antithrombin III, proteins C and S)
4. Hyperlipidaemia: increased risk of atherosclerotic
vascular disease
5. Chronic renal insufficiency, failure
36

37. PREVENTION
 General health education
 Specific protection
 Early diagnosis and treatment
 Limitation of disability
 Rehabilitation
37

38. PROGNOSIS
 Nearly 80% of children with MCNS experience relapse
(heavy proteinuria that persists for 3 or more
consecutive days)
 Steroid responsive patients have little risk of chronic
renal failure
 FSGS: may initially respond to steroids, later not
respond, may progress to end stage renal failure
 Recurrence of FSGS occurs in 30% of children who
undergo renal transplantation
38

39. S.M.
M
4yrs 2/12
39

40. 40

41. 41

42. CONCLUSION
 Nephrotic Syndrome is a manifestation of glomerular
disease characterized by heavy proteinuria,
hypoalbuminaemia, hypercholesterolaemia and oedema
 Most children with NS have a form of primary or
idiopathic NS
 Children between 1 and 8 years with uncomplicated NS
are likely to have steroid responsive MCNS, steroid
therapy may be commenced without renal biopsy
 Nearly 80% of them will experience relapse 42

43. REFERENCES
 Nelson Textbook of Paediatrics, 19th Edition; Chapter 521: Nephrotic
Syndrome
 Nelson Essentials of Paediatrics, 6th Edition; Chapter 162: Nephrotic
Syndrome and Proteinuria
 Current Paediatric Diagnosis and Treatment, 15th Edition; Chapter 21, pg 616:
Idiopathic Nephrotic Syndrome of Childhood
 Paediatric and Child Health in a Tropical Region by Azubuike and
Nkanginieme, 2nd Edition; Chapter 59: Nephrotic Syndrome and Acute
Glomerulonephritis
 Renal Medicine; History of Nephrotic Syndrome:
http://www.renalmed.co.uk/history-of/nephrotic-syndrome
 Wikipedia; Nephrotic Syndrome:
http://en.wikipedia.org/wiki/Nephrotic_syndrome
43

44. THANKS
FOR
LISTENING!!!
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