Tuesday 4th January 2011
Dr Matthew Home
NEPHROTIC SYNDROME
CASE PRESENTATION
CONTENTS
Case presentation
 Definition
 Causes
 Guidelines
 References

PREVIOUS HISTORY
Born AGH
 Term (40 weeks)
 Apgars 71 / 95
 Well since
 Immunisations
up-to-date

Four brothers (8, 11,
16, 17 yrs) all well
 No regular
medications
 NKDA

PRESENTATION
S/B GP ~14/09/2010
 Facial swelling – particularly periorbitally
 Loss of Appetite
 Flu symptoms (Rhinorheoa, Fevers) a few
weeks before
Arrange bloods and follow-up appointment
Follow-up appointment not attended
S/B GP again on 04/10/2010
 Abdominal pain and distension
 Ankle swelling
 Continued loss of appetite
 “Drinking plenty of fluids”
 Increased urine volume
 No
dysuria, haematuria or offensive urine
Bowels - trace blood (Recent prolapse)
 No rash, fever

BLOODS / URINE DIP (14/09/2010)
Haemoglobin
White Cell Count
Platelets
13.4
8.8
492
g/dL
x109/L
x109/L
11.5 - 17.5
3.7 - 15.5
140 - 450
Sodium
Potassium
Bicarbonate
Urea
Creatinine
Chloride
135
4.4
24.5
2
18
106
mmol/L
mmol/L
mmol/l
mmol/L
umol/L
mmol/L
132 - 143
3.2 - 5.7
13 - 29
1.8 - 9.6
27 - 88
96 - 114
Calcium
Total Protein
Albumin
ALT 12
Alkaline Phosphatase
Total Bilirubin
2.07
35
less thn 10
IU/L
118
6
mmol/L
g/l
2.14 - 2.62
56 - 77
Nov-39
IU/L
umol/L
110 - 302
0 - 34
Vitamin D
Free T4
Ferritin
TSH 8.58
17
8.7
19
miu/L
nmol/L
60 - 150
pmol/L
7.5 - 21.1
ng/mL
14 - 180
0.34 - 5.6
EXAMINATION

P 118, BP 109/63,
SaO2 99% RA


Chest – Clear
HS - I + II + 0
ENT - NAD

Abdomen




moderately distended
(Ascites)
No palpable L/S/K/K
Peripheral odema +
BLOODS ON ADMISSION (04/10/2010)
Haemoglobin
White Cell Count
Platelets
13.7
7.7
437
g/dL
x109/L
x109/L
3.7 - 15.5
140 - 450
11.5 - 17.5
Sodium
Potassium
Bicarbonate
Urea
Creatinine
Chloride
136
4.1
23.8
3.2
13
105
mmol/L
mmol/L
mmol/l
mmol/L
umol/L
mmol/L
132 - 143
3.2 - 5.7
13 - 29
1.8 - 9.6
27 - 88
96 - 114
Calcium
Total Protein
Albumin
Corrected Calcium
Globulin
ALT
Alkaline Phosphatase
Total Bilirubin
2.21
47
16
2.69
31
18
91
8
mmol/L
g/l
g/L
mmol/L
g/L
IU/L
IU/L
umol/L
2.14 - 2.62
56 - 77
31 - 48
2.14 - 2.62
23 - 41
11-39
110 - 302
0 - 34
mmol/L
IU/mL
miu/L
pmol/L
3.0 - 12.0
0 - 200
0.34 - 5.6
7.5 - 21.1
Blood Culture (Aerobic): No growth (5 days)
VZV IgG Antibodies
Plasma Glucose
Antistreptolysin-O
TSH
Free T4
Thyroid Peroxidase
Positive
4.8
1
10.72
7.5
Less than 10
URINE DIP
Protein +++
DIAGNOSIS
1.
2.
Nephrotic Syndrome
Vitamin D Deficiency
NEPHROTIC SYNDROME DEFINITION
Nephrotic range proteinuria (> 1g/m2/day)
 Hypoalbuminaemia (<25 g/l)
 Oedema

Classification
 Idiopathic (primary) nephrotic syndrome
Minimal change (80-90%)
 Focal segmental glomerulosclerosis (FSGS) (10-20%)

Secondary nephrotic syndrome (HSP, SLE, MPGN)
 Congenital nephrotic syndrome

MINIMAL-CHANGE DISEASE (MCD)



Also known as lipoid
nephrosis or nil disease
It refers to a
histopathologic lesion in
the glomerulus
Disorder of T cells,
which release a
cytokine that injures the
glomerular epithelial
foot processes.
FOCAL SEGMENTAL GLOMERULOSCLEROSIS

?viral- or toxin-mediated
damage or intrarenal
hemodynamic changes
such as hyperperfusion
and high
intraglomerular capillary
pressure
1.
2.
3.
Injury to podocytes
shrinkage/collapse of
glomerular capillaries
scarring
(glomerulosclerosis)
NEPHROTIC SYNDROME - CAUSES

Idiopathic NS






MCNS
FSGS
MPGN
Membranous glomerulonephritis (MGN)
IgA nephropathy
Idiopathic crescentic glomerulonephritis

Secondary nephrotic syndrome

Infections





Drugs


Genetic nephrotic syndrome/congenital nephrotic
syndrome











Finnish-type congenital nephrotic syndrome (NPHS1,
nephrin)
Denys-Drash syndrome (WT1)
Frasier syndrome (WT1)
Diffuse mesangial sclerosis (WT1, PLCE1)
Autosomal recessive, familial FSGS (NPHS2, podocin)
Autosomal dominant, familial FSGS (ACTN4, α-actinin4; TRPC6)
Nail-patella syndrome (LMX1B)
Pierson syndrome (LAMB2)
Schimke immuno-osseous dysplasia (SMARCAL1)
Galloway-Mowat syndrome
Oculocerebrorenal (Lowe) syndrome








Congenital syphilis, toxoplasmosis, cytomegalovirus, rubel
la
Hepatitis B and C
HIV/acquired immunodeficiency syndrome (AIDS)
Malaria
Penicillamine
Gold
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Interferon
Mercury
Heroin
Pamidronate
Lithium
Systemic disease




Systemic lupus erythematosus
Malignancy - Lymphoma, leukemia
Vasculitis -Wegener granulomatosis, Churg-Strauss
syndrome, polyarteritis nodosa, microscopic polyangiitis,
Henoch-Schönlein purpura (HSP)
Immune-complex–mediated - Poststreptococcal
glomerulonephritis
NEPHROTIC SYNDROME - IDIOPATHIC
Typical Features
Atypical Features
Age 1-10 years
<1yr, >10years
Normotensive
Hypertensive
Normal Adrenal Function
Elevated Creatinine
+/- microscopic
haematuria
Macroscopic Haematuria
NEPHROTIC SYNDROME - INVESTIGATIONS







Blood: FBC, U+E’s; Creatinine; LFT’s; ASOT; C3/C4; Varicella
titres
Urine: Urine culture and Urinary protein/creatinine ratio
BP
Urinalysis including glucose
A urinary sodium concentration can be helpful in those at
risk of hypovolaemia.
Varicella status should be known in all children commencing
steroids.
Hepatitis B status may be appropriate in children at high
risk.
NEPHROTIC SYNDROME - REFERRAL
Age < 1 yr
 Age > 10-12 yrs
 Persistent hypertension
 Macroscopic haematuria
 Low C3/C4
 Failure to respond to steroids within 4 weeks

NEPHROTIC SYNDROME - COMPLICATIONS

Hypovolaemia
 Despite

Infection
 Loss

odema may be intra-vascularly depleted
of complement components
Thrombosis
 Loss
of proteins and exacerbated by hypovolaemia
TREATMENT

Prednisolone

Penicillin prophylaxis

Salt/Fluid Restriction

Vaccination
+/- Ranitidine

Albumin where
indicated
+ Frusemide midinfusion
MONITORING
Remission – 3+ days of trace / - protein on
dipstick testing
Up to 60 - 70 % of children may have one or more
relapse.
Urine check twice weekly initially, then weekly
TREATMENT OF RELAPSING NS
Prednisolone
 Albumin
 Salt Restriction
 Penicillin
 Varicella vaccine

 Consider
between relapses in children who are
varicella seronegative.
REFERRAL OF RELAPSING NS
Referral to / Discussion with Paediatric
Nephrology if
Frequent relapsers
 Steroid dependency
 Steroid toxicity

FREQUENT RELAPSES
Frequent relapsers are diagnosed if there is:
 2 or more relapses within the first 6 months of
presentation
 4 or more relapses within any 12 month period
This becomes steroid dependency if the relapses
are occurring during steroid tapering.
 Varicella status should be repeated 6 monthly in
those who are non-immune.

TREATMENT OF FREQUENT RELAPSES
Low Dose Alternate Day Prednisolone
 Levamisole
 Cyclophosphamide
 Cyclosporin
 Mycophenylate Mofitil (MMF)

OUR CASE - PLAN





Prednisolone 60mg/m2
Ranitidine
Penicillin V
Dalavit Vit D Suppliments
HAS 20% @ 5ml/kg with Frusemide 1mg/kg half way through x3

Urinalysis with each void
Monitor daily urine output
Daily weights – adjust fluid restriction accordingly
Fluid restrict to 600ml/day

D/W Leeds renal team



CASE PROGRESS
Review 15/10/10
 Odema settled
 Persistent Proteinuira Pro+++
 Penicillin V stopped
 Continue Prednisolone
Review 29/10/10
 Persistent Pro+++
 Prednisolone changed to
40mg/m2 - 25mg alt days
Review 22/10/10
 Odema settled
 Persistent Proteinuira Pro+++
 Penicillin V stopped
 Continue Prednisolone
Review 13/11/10
 Persistent Pro+++
 Restart Penicillin V 125mg BD
 Referred to Paediatric renal team
for ?renal biopsy
REFERENCES
www.gpnotebook.co.uk/
 http://emedicine.medscape.com/
 http://www.clinicalguidelines.scot.nhs.uk/
 www.newcastle-hospitals.org.uk/
