Case Presentation Congenital Nephrotic Syndrome : 19/10/2009 Paediatric Meeting/RI/Dr V Wright 1 DR VICTORIA WRIGHT
ST 2 GP VTS Case Presentation Congenital Nephrotic Syndrome
Case Presentation CE : 19/10/2009 Paediatric Meeting/RI/Dr V Wright 2 Case Presentation CE Background: 2 Year Old Girl
Congenital Nephrotic Syndrome
(Nov 2007)
Bilateral Nephrectomy (April 2009)
Peritoneal Dialysis APD
Hypothyroidism
Factor 12 Deficiency
Febrile Convulsions (Feb 2009)
Case Presentation CE : 19/10/2009 Paediatric Meeting/RI/Dr V Wright 3 Case Presentation CE PC
‘Generally unwell’
HPC
Came 2 days before, treated for tonsillitis with Pen V, improved then worsened again
Clingy (5 days, worsened day of admission)
Off feeds and not drinking (1 day)
1 x Vomit, No Diarrhoea
Not been taking medications (2 days)
Case Presentation CE : 19/10/2009 Paediatric Meeting/RI/Dr V Wright 4 Case Presentation CE Medication (NKDA)
Levothyroxine
Penicillin V
Sytron
Alfacalcidol
Calcichew
EPO
Abidec
Peritoneal Dialysis every night
Case Presentation CE : 19/10/2009 Paediatric Meeting/RI/Dr V Wright 5 Case Presentation CE Immunisations
Up to Date
Development
?‘A little slow’ reviewed and follow up not required
Social History
Only child, lives with mum and dad, very knowledgeable
Family History
No renal conditions
Mum had fits has a child after meningitis
Birth History
36 wks, NVD, 2.81kg, no antenatal concerns, low BM at birth discharge on day 2
Case Presentation CE : 19/10/2009 Paediatric Meeting/RI/Dr V Wright 6 Case Presentation CE On Examination
Temp 35.5, HR 108, RR 32, BP 86/43, Sats 96%, Weight: 10kg, Cap refill normal, looking around
Looked unwell, crying, ‘floppy’, moving all four limbs
HS Normal & No murmur
Chest clear
Abdo soft and non tender
Ears NAD
Case Presentation CE : 19/10/2009 Paediatric Meeting/RI/Dr V Wright 7 Case Presentation CE Then
Started having a left sided focal seizure
A - Maintained
B - Chest still clear, RR 25
C - HS Normal with no murmur, HR 125
D - Responding to Voice
E - Temp 36.3, BM 15
Case Presentation CE : 19/10/2009 Paediatric Meeting/RI/Dr V Wright 8 Case Presentation CE Management plan
Buccal Midazolam (5 mg)
Reassessed:
A - Maintained – O2 given
B - RR 35, Sats 98% on 5 L , CXR requested
C - HS I&II&O, HR 125, Monitored, cannulated (FBC, U&E, LFT, Ca, Mg, INR, glucose, cultures, gases), fluids given (2/3rd maintenance)
D - Responding to Voice
E -Temp 36.4, peritoneal fluid for culture
Case Presentation CE : 19/10/2009 Paediatric Meeting/RI/Dr V Wright 9 Case Presentation CE Differential Diagnosis
Febrile convulsion (Atypical)
Electrolytes disorder
Infection +/- involving the central nervous system
Focal bleed
Case Presentation CE : 19/10/2009 Paediatric Meeting/RI/Dr V Wright 10 Case Presentation CE Treatment
Antibiotic (Cefotaxime)
Antiviral (Acyclovir)
Moved to HDU
Case Presentation CE : 19/10/2009 Paediatric Meeting/RI/Dr V Wright 11 Case Presentation CE Blood results
Hb 7.1
WCC 7
MCV 84
PLT 384
INR 1
Urea 15.7 (baseline 11.2)
Creatinine 488 (base line 374)
K 5.8
Na 133
Mg 1.06
Ca 2.38
Albumin 33
CRP 21.4
Glucose 8.8 Venous Gases
PH 7.461
pCO2 5.84
Po2 7.26
HCO3 30.5
BE 6.7
CXR – Normal
Peritoneal fluid - No growth, Normal WCC
Case Presentation CE : 19/10/2009 Paediatric Meeting/RI/Dr V Wright 12 Case Presentation CE What happened next:
Started on dialysis,
? Needed urgent CT scan ? Needed LP
D/W Renal Team
Transferred to RMCH
Left sided hemiparesis, urgent MR scan, EEG, LP (blood stained), Cultures –ve, started on phenytoin and aspirin
Discharged: Seizure, ‘Cause unknown’
Nephrotic Syndrome in Children : 19/10/2009 Paediatric Meeting/RI/Dr V Wright 13 Nephrotic Syndrome in Children
Nephrotic Syndrome in Children : 19/10/2009 Paediatric Meeting/RI/Dr V Wright 14 Nephrotic Syndrome in Children Caused by renal diseases that increase the permeability across the glomerular filtration barrier
Classically characterized:
Nephrotic range proteinuria — Urinary protein to creatinine ratio >200mg/mmol
Hypoalbuminaemia — Serum albumin concentration less than 25 g/L
Oedema
Hyperlipidemia
Nephrotic Syndrome in Children : 19/10/2009 Paediatric Meeting/RI/Dr V Wright 15 Nephrotic Syndrome in Children Other features:
Hypertension (rarely)
Foamy urine
May have features of the underlying cause (ie rash : SLE, HSP)
Examination should also exclude other causes of oedema
Nephrotic Syndrome in Children : 19/10/2009 Paediatric Meeting/RI/Dr V Wright 16 Nephrotic Syndrome in Children Commonest glomerular disease of childhood
Incidence is 2-3:100,000 per year
Median age at presentation 4 years
More common in males than females (ratio 3:2)
Nephrotic Syndrome in Children : 19/10/2009 Paediatric Meeting/RI/Dr V Wright 17 Nephrotic Syndrome in Children
Nephrotic Syndrome in Children : 19/10/2009 Paediatric Meeting/RI/Dr V Wright 18 Nephrotic Syndrome in Children Presentation
Non specific presentation (URTI, with onset of oedema, lethargic, irritable and have poor appetite, diarrhoea and abdominal pain)
periorbital, genital and/or dependent oedema
Transudative ascites – (esp in children)
Pleural effusions
Abdominal discomfort (hypovolaemia, ascites or peritonitis)
Diarrhoea and/or vomiting
Nephrotic Syndrome in Children : 19/10/2009 Paediatric Meeting/RI/Dr V Wright 19 Nephrotic Syndrome in Children Investigations
Urine dipstick analysis (protein and blood)
Protein:creatinine ratio
Urine ( microscopy, sensitivity and culture)
Serum electrolytes, albumin, triglyceride and cholesterol, calcium
FBC
Complement C3 and C4 levels
Varicella zoster serology
Hepatitis B and C serology
? Atypical presenting features: ASO titre, anti-DNAse B, lupus antibody serology (ANA, ENA, ds- DNA), ANCA
Finding of heavy proteinuria (3-4+) on dipstick and oedema in a child in the developed world usually means a diagnosis of Nephrotic syndrome
Nephrotic Syndrome in Children : 19/10/2009 Paediatric Meeting/RI/Dr V Wright 20 Nephrotic Syndrome in Children Treatment
The majority of children with nephrotic syndrome will respond to steroid therapy
Symptomatic management
Is important in the early course of therapy as response to steroid therapy may take several weeks
It is the mainstay of therapy in children who fail to respond to steroids
Symptomatic management
Persistent proteinuria: salt and fluid restriction, and diuretics
Prevention of thromboembolic complications: mobilization, hydration, and early treatment of sepsis or volume depletion
Infections: pneumococcal and varicella vaccines
Persistent hypertension are more likely to have chronic kidney disease with poor outcome, ACE inhibitors or angiotensin II receptor blockers
Nephrotic Syndrome in Children : 19/10/2009 Paediatric Meeting/RI/Dr V Wright 21 Nephrotic Syndrome in Children Complications
Hypovolaemia
Renal vein thrombosis
Arterial thrombosis
Infection
Iron deficiency due to loss of transferrin and iron
Muscle wasting
Accelerated atherosclerosis
Indications for Renal Biopsy
<12 months, >12 years
Increased BP
Macroscopic haematuria
Impaired renal function
Decreased C3/4
Failure to respond after 1 month of steroid therapy
Nephrotic Syndrome in Children : 19/10/2009 Paediatric Meeting/RI/Dr V Wright 22 Nephrotic Syndrome in Children The prognoses
Minimal change disease
A third have just one episode
A third have infrequent relapses
A third have frequent relapses throughout childhood which abate during adulthood; life expectancy is normal
Focal segmental glomerulosclerosis
A third remit after a prolonged course
A third have continuing haematuria and proteinuria but have normal renal function
A third progress to end stage renal failure
Congenital Nephrotic Syndrome : 19/10/2009 Paediatric Meeting/RI/Dr V Wright 23 Congenital Nephrotic Syndrome
Congenital Nephrotic Syndrome : 19/10/2009 Paediatric Meeting/RI/Dr V Wright 24 Congenital Nephrotic Syndrome Congenital Nephrotic syndrome is very rare
Presents at birth or within the three first months of life
Later onset, between three months and one year of age, is called infantile nephrotic syndrome
Most of these children have a genetic basis for the renal disease and a poor outcome
The precise diagnosis of the glomerular lesion is based on clinical, laboratory and histological criteria
Congenital Nephrotic Syndrome : 19/10/2009 Paediatric Meeting/RI/Dr V Wright 25 Congenital Nephrotic Syndrome Primary
Congenital Nephrotic Syndrome – ‘Finnish’ Microcyctic disease
Diffuse Mesangial Sclerosis
Minimal change nephrotic syndrome
Focal Segmental glomerulosclerosis
Drash syndrome
Secondary
Syphilis
Toxoplasmosis
Cytomegalovirus
Mercury
Nail-Patella Syndrome
Congenital Nephrotic Syndrome : 19/10/2009 Paediatric Meeting/RI/Dr V Wright 26 Congenital Nephrotic Syndrome Symptoms
Low birth weight
Large placenta
Swelling (total body)
Decreased urine output
Foamy appearance of urine
Poor appetite
Cough
Congenital Nephrotic Syndrome : 19/10/2009 Paediatric Meeting/RI/Dr V Wright 27 Congenital Nephrotic Syndrome Treatment
Early and aggressive treatment
Diuretics
ACE inhibitor
Non-steroidal anti-inflammatory drugs
Antibiotics may be needed
Dietary modifications
Fluids restriction
Removal of the kidneys, dialysis, and kidney transplant may be required
Congenital Nephrotic Syndrome : 19/10/2009 Paediatric Meeting/RI/Dr V Wright 28 Congenital Nephrotic Syndrome Prognosis
Many fatal within the first year
May be successfully controlled with early and aggressive treatment, including early kidney transplantation
Complications
Frequent, severe infections
Malnutrition and related diseases
Thrombosis
Acute kidney failure
Chronic kidney failure
End-stage kidney disease
Congenital Nephrotic Syndrome – ‘Finnish’ Microcyctic Disease : 19/10/2009 Paediatric Meeting/RI/Dr V Wright 29 Congenital Nephrotic Syndrome – ‘Finnish’ Microcyctic Disease Autosomal Recessive Inheritance
1.2:10,000 births in Finland (With prenatal screening, the incidence has fallen to 0.9 per 10,000 births)
Massive proteinuria at birth – enlarged placenta
Severe outcome
Due to mutations in the NPHS1 Gene encoding nephrin
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