Nephrotic Syndrome in

children
Dr Chisambo Mwaba,2016
Objectives
1.Define nephrotic syndrome
2.Describe causes of nephrotic syndrome in children
3.Pathophysiology of nephrotic syndrome
4.Investigations
5.Complications
6.Clinical assessment
7.Treatment of nephrotic syndrome
What is the nephrotic syndrome?
• Not a disease, it’s the occurrence of four features in a patient which
results from massive loss of protein in the urine

Odema
Proteinuria-Nephrotic range
Hypertriglyceridemia/hypercholesteremia
Hypoalbumineamia <25g/L
Classification –age based
1. Congenital nephrotic syndrome- occurs before 3 months of age
2. Infantile nephrotic syndrome- 3 months to 1 year
3. Childhood nephrotic syndrome
Causes/ Aetiological classification
• Congenital Nephrotic syndrome
 TORCHES
NPHS1 and NPHS2 mutations
Syndrome associated e.g nail-patella syndrome, Galloway-mowatt,
Frasier, pierson, denys-drash
Autoimmune e.g sle, maternal anti endopeptidase
Drug reaction
Causes
• Childhood Nephrotic syndrome
Idiopathic-90%
Genetic
Infections- HIV, HCV,HBV (viral), malaria, leshmaniasis (parasites),
syphilis, infected shunt, SABE (bacterial)
Malignancy- Hodgkin's lymphoma
Autoimmune/connective tissue disease- SLE, Wagener's
granulomatosis, microscopic polyangiitis, IgA nephropathy, HSP
Drugs/toxins e.g mercury, lead, NSAIDS
IDIOPATHIC NEPHROTIC SYNDROME
• 90 % of childhood nephrotic syndrome
• Associated with non-specific abnormalities of kidneys including
FSGS,MCD,MP-mesangioproliferative
• Fusion of epithelial foot process on EM
• No significant immune deposits on immunoflorescence
Normal glomerulus
Minimal change
Focal Segmental Glomerulosclerosis
Mesangial proliferation
IDIOPATHIC NEPHROTIC SYNDROME
• Commonly 2-7 year olds
• Boys> girls
• More common in asians
PATHOPHYSIOLOGY
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THE GLOMERULAR FILTRATION
BARRIER
Pathophysiology :
The split diagram
Pathophysiology of protein loss and
hypoalbuminaemia
• Increased amounts of albumin in the urine as a result of dysfunctional
filtration barrier- genetic or immunological
• This overwhelms the proximal tubules capacity to reabsorb albumin
thus appearing in the urine.

Nephrotic range proteinuria

-24 hour urine collection- > 40mg/m2/hr or > 50 mg/kg/day
-urine protein /creatinine ratio-0.2g/mmol or > 2g/g
-dipstick-
Other proteins that are lost through the
glomerulus and the consequences
• Thyroid binding protein
• Insulin like growth factors
• Anti-coagulation proteins
• Immunoglobulins
• Complement proteins
Pathophysiology of oedema
• Underfill theory
• Overfill theory
Pathophysiology:
Hyperlipidaemia
• Increased hepatic synthesis of of cholesterol,trigylcerides,lipoproteins
• Decreased catabolism of lipoproteins- deficiency lipoprotein lipase
COMPLICATIONS OF NEPHROTIC
SYNDROME
• Thrombo-embolic phenomena
• Infections
• Renal failure
• Cardio-vascular disease
Patient assessment
• ABC
• Systemic approach in both history and examination
Investigations
• FBC
• UEC,LFT, lipid profile
• CXR, mantoux, varicella zoster IgG levels, measles IgG levels
• ANA,C3/C4, HBV,HCV,HIV,RPR
• +/_ renal biopsy
TREATMENT-STEROID SENSITIVE NS
STEROID SENSITIVE NEPHROTIC SYNDROME

FREQUENT INFREQUENTLY
RELAPSING RELAPSING

STEROID DEPENDANT
First episode SSNS
• Treat for total 12 weeks
-2mg/kg or 60mg/m2/day OD for 4 weeks
- 1.5 mg/kg or 40 mg/m2 alt day for 4 weeks
- taper steroids over 4 weeks
Some useful terms to remember
• Remission –negative or trace dipstix proteinuria for 3 or more days
• Relapse – 2+ or more proteinuria on dipstick for 3 or more days
• Steroid resistant nephrotic syndrome- failure of proteinuria to resolve
following at least 28 days of prednisolone at a dose of 60 mg/m2/day.
• Steroid dependant nephrotic syndrome—children who relapse while
onsteroid therapy or within 14 days of discontinuation of steroid therapy.
• Frequently relapsing nephrotic syndrome—children whorelapse two or
more times in the first 6 months after presentation or four times or more
within any 12-month period
.Oxford sub-specialist handbook in paediatric nephrology
Infrequently relapsing- treating relapse
• prednisolone 60 mg/m2/day or 2mg/kg/day until dipstick negative or
trace 3 days continuously
• Then 40 mg/m2/day or 1.5 mg/kg/day alternate day for 4 weeks
• Taper over 4 weeks
Steroid dependant or frequently relapsing
• Steroid to as low a dose as possible without side effects as long as
responsive
if unresponsive

• +/- biopsy
• Levimasole 2.5 mg/kg/ alt day for 2 years
• Alkylating agents e.g chlorambucil, cyclophosphamide
• Calcineurin inhibitors e.g cyclosporine, tacrolimus
• Biologics e.g Rituximab anti-CD 20 antibody ( depletes B cells)
STEROID RESISTANT NS

• Biopsy +/- genetic studies

• Calcinurein inhibitors or alkylating agents
• Anti-proteinureic measures
• Diuretics