Oke Rina Ramayani

Departement of Pediatrics
H Adam Malik General Hospital/ Faculty of Medicine
North Sumatera University - Medan

Education
• Medical doctor : Faculty of Medicine, North Sumatera University 1997
• Doctoral : Faculty of Medicine, North Sumatera University
• Pediatrician : Departement of Child Health, Faculty of Medicine, North
Sumatera University, 2005
• Consultant : Nefrology of Indonesian Pediatric College 2013
Position
MB
Organization
Indonesian Pediatric Society
Complicated Nephrotic Syndrome

Oke Rina Ramayani

Pediatric Department, University of Sumatera Utara
Introduction
• Nephrotic syndrome (NS)
• Commonest glomerular
disease affecting
children
• Frequently encountered
in general paediatrics
• A boy, 7th y.o with oedema
for first time
• Massive proteinuria
• Hipoalbuminemia
• Hypercholesterolemia
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 What happens in NS?
Hypoalbuminemia

Reduced intravascular oncotic pressure

Loss of fluid into intrerstisial

space
Increased albumin production Reduced plasma volume
and lipoprotein synthesis
Increased serum tryglyseride Increased aldosterone Decreased renal function
& low density lipoproteins secretion
Salt and water retention
Lipiduria Oedema
Complicated NS

Related to Related
reduced to loss of
oncotic proteins
pressure in urine

Related to
therapy

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 COMPLICATIONS

Due to ↓ oncotic Due to loss of

pressure proteins in the urine

• Hypovolemia  ARF • Immunoglobulin

• Anasarca ↑susceptibility to infection
risk of cellulitis, • Antithrombin III & proteins C,S
bacterial peritonitis/SBP  thromboembolism
large pleural effusions or • Vit D–binding protein  vit D def
pulmonary edema • Transferrin Iron deficiency
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The five major complication related
to underlying NS
• Infection
• Hipovolemic crisis
• Acute renal failure
• Tromboembolism
• Anasarca

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Infection
• In children with NS, Streptococcus pneumoniae is known to be the
most important organism in primary peritonitis.
• Other organisms such as
β-hemolytic streptococci,
Haemophilus and
Gram-negative bacteria are also frequently found.
• Cellulitis is also the result of β-hemolytic streptococci or a variety
of Gram-negative bacteria.

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 Management of common infection
Infection Clinical features Common organism Treatment

Peritonitis Abdominal pain, S. pneumoniae, Cefotaxime or Ceftriaxone

tenderness, diarrhoa, S.pyogenes, E. coli Ampi + Aminoglycoside
vomiting
Pneumonia Fever, tachypnea, S.pneumoniae Ceftriaxone or Ampi +
cough H.influenzae Aminoglycoside
Amoxicillin or Coamoxiclav
for mild
Cellulitis Redness, tenderness or β haemolytic streptococci, Ceftriaxone with Cloxacillin
induration H.influenzae, pneumococci, followed by oral cloxacillin
staphylococci and cefixime

Practical Ped Nephrology, 2005

Prevention
• These children must be vaccinated against these bacteria because
of waning immunity over time
• Patients undergoing treatment for NS with immunosuppressants are
also at continued risk of infections, and febrile illnesses in this
population require close follow-up.

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Anasarca
• Ascites and pleural effusions frequently occur
• Pericardial effusion is rare unless cardiac
function is abnormal.
• Severe/symptomatic oedema – potential skin
breakdown/cellulitis, gross scrotal/vulval
oedema, increased work of breathing from
pleural effusion
• Oedema is caused by increased glomerular
permeability and hypoalbuminemia, resulting
in decreased plasma oncotic pressure and
functional hypovolemia.
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Hypovolemic Crisis
• Risk factors for hypovolemic crisis include severely Ouch.
depressed albumin levels, high dose diuretics, and .very

vomiting.
sick

• The clinical manifestations:

• tachycardia,
• cold extremities,
• poor capillary refill, and
• moderate to severe abdominal pain

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Acute Renal Failure
• Acute renal failure (ARF) is an alarming complication of
nephrotic syndrome (NS).
• Causes include:
• rapid progression of glomerular disease
• renal vein thrombosis
• interstitial nephritis (antibiotics, diuretics, NSAIDs).
• haemodynamic derangements .

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How to differentiate circulation volume?

Circulation volume Circ. volume Decreased

Normal
Difference core to peripheral < 2 °C > 2 °C
temperature
Acral red bluish
Capillary refill time < 2 sec > 2 sec
Heart rate Normal Increased
Blood pressure Normal Decreased
urine output volume Normal Decreased
urine sodium > 20 mmol/L < 10 mmol/L
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Management
Assess severity of oedema

Moderate/severe,symtomatic Mild,asymtomatic
Fluid restriction
Assess intravascular volume status Dietary sodium restricton
Monitoring body weight
Intravascular expansion Intravascular depletion
Fluid restriction
Hypotension Normotension
Furosemide and spironolactone
10 ml/kg 0.9% NaCl or
4.5% albumin 20% albumin over 4 hours
Double doses furosemide
10 ml/kg 0.9% NaCl or
Add HCT
4.5% albumin
Iv bolus furosemide or infusion
PICU Pediatr Nephrol ,2014
20% Albumin + furosemide
Thromboembolism (TE)

Indirect • Children >12 years of

• Platelet hyper-
aggregability
mechanism age
• Hypercoagulation • Congenital NS
• Hyperviscosity • Severe proteinuria
• Decreased endogenous
anti-coagulants • Hyperlipidemia • Previous episodes of
• Decreased activity of • RBC hyperaggregation thrombosis/DVT
fibrinolytic system • Central line access
• Endothelial cell injury

Significant
Pathogenesis association
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 TE LOCATION AND MANAGEMENT
• Deep vein thrombosis, pulmonary embolus
• Renal vein thrombosis – macroscopic
haematuria, palpable kidney, loin tenderness,
raised creatinine, hypertension
• Cerebral vein thrombosis - headache,
vomiting, impaired conscious state or focal
neurology
• Early aggressive heparin therapy followed by
oral anticoagulants is necessary for a
favorable outcome.
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 Calsium & vit.D metabolism alteration
• Hypocalcemia is also attributed to the decreased albumin level, which
results in reduced bound and ionized calcium in 50 to 80% of cases
• Children with NS often have hypocalciuria due to decreased
gastrointestinal absorption of calcium and increased renal tubular
reabsorption of calcium.
• The possibility of an abnormality in vitamin D metabolism due to
increased filtration of vitamin D metabolites bound to vitamin D-binding
globulin.

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Management
• However, bone disease is rarely shown in NS
patients, and therefore, routine treatment with vitamin
D is not recommended.
• Nevertheless, special concern should be given to
subclinical mineral bone disorder like secondary
hyperparathyroidism

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Management complication due to CS
• Adrenal suppression • alternate day therapy.
• Impairment of growth • sparing agents, GH th/
• Osteoporosis • Calcium, vitamin D suppl
• Peptic ulceration • H2 blockers
• Hypertension • anti-hypertensive agents
• Catarac • low dose CS, opthalmology
consult
• Behavioral changes
• reduce or withdraw CS.

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Complication related to CPM
• bone marrow suppression
• alopecia Check list at clinic:
• gastrointestinal upset, CBP and reticulocyte count
Urine for RBC
• hemorrhagic cystitis, and Pubertal change/menstruation
infections pattern in pubertal girl
• late complications of Fertility issue
possible malignancies
• impaired fertility, .
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Management related to CPM
• There is a dose-dependent relationship between sperm
counts and the cumulative dose of CPM.
• To avoid gonadal toxicity, CPM should not be used for
more than 12 weeks (2 mg/kg, single oral dose)
• should be withheld if the white blood cell count is less
than 5,000/mm3during CPM use.
• High fluid intake is recommended to elude hemorrhagic
cystitis.
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Complication related to CsA

 Nephrotoxic
 Liver dysfunction. Check list at clinic:
 Hypertension,  RFT, K+, Mg ++
hyperkalemia.  Serum CsA
 Hyperglycemia.
 Consider renal biopsy
 Viral infections
 Predispose to cancer.
 Hirsutism
 Neurotoxicity (tremor).
 Gum hyperplasia.
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 Management related to CsA
• The lowest effective dose of CsA is recommended for the
maintenance treatment in NS , with slow tapering over one
year to 1 to 3 mg/kg/day.
• The combined treatment of CsA and MMF did not prevent the
development of chronic CsA nephrotoxicity, but MMF
treatment after CsA withdrawal improves chronic CsA
nephrotoxicity.

Fujinaga S et al.Arch Dis Child. 2006;91:666–670.

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Yang et al. Kidney Int. 2002;62:20–30
Measure to control complicated NS
 Edema control
 Judicious use of diuretics
 Severe cases : iv albumin
 Antibiotics if needed
 Immunization for prevention
 Dietary protein according to RDA
 Vit D supplementation if indication
 Anticoagulant for TE
 Known adverse effect of drug and follow up

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Thank you