Nephrosis and Nephritis
Dr M White, Paediatric SpR
TCD Lecture
Mon 11th May 2009
1) Nephrotic Syndrome
2) Glomerulonephritis
Nephrotic Syndrome
Nephrotic Syndrome
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Characterised by proteinuria (3.5g
per 24 hours), hypoalbuminemia
(serum <30g/dL), oedema,
hypercholesterolemia
Almost always idiopathic in childhood
Classification
 Primary
vs Secondary
 Histology
 Therapeutic
Primary Nephrotic Syndrome
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Post-infectious aetiologies
Congenital Nephrotic Syndrome
Collagen vascular disorders (SLE/RA/PAN)
Henoch-Schonlein Purpura
Hereditary Nephritis
Sickle cell disease
Diabetes Mellitus
Amyloidosis
Malignancy
Secondary Nephrotic Syndrome
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Group A beta-haemolytic strep
Syphilis
Malaria
TB
Viral infections (varicella, HBV, HIV-1,
infectious mononucleosis)
Histological Classification
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Minimal-change nephrotic syndrome
(MCNS) = 84.5%
Focal Segmental glomerulosclerosis
(FSGS) = 9.5%
Mesangial proliferation = 2.5%
Membranous nephropathy & others =
3.5%
Therapeutic Classification
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Steroid sensitive (85-90%)
Steroid resistant (10-15%)
Steroid dependent
Frequently relapsing
Pathophysiology
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Two important issues; 1)mechanism of
glomerular injury 2)proteinuria
Circulating non-immune factors in MCD and
FSGS
Circulating immune factors in disorders
membranoproliferative GN, poststreptococcal GN
and SLE nephritis
Mutations in podocyte or slit diaphragm in
inherited form of congenital, infantile or
glucocorticoid resistant nephrotic syndrome
Incidence = 2-7 cases per 100,00 per
year
 15 times more common in children
than adults
 Age of onset varies with type of
disease
 Mortality rate related to primary
disease process
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Definitions
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Remission – negative urinalysis on 1st
morning urine for 3 consecutive mornings
Relapse – 3+ proteinuria on 3 or more
consecutive 1st morning urines
Frequently relapsing – 2 or more relapses
within 6 months of diagnosis; or 4 or more
relapses per year
Steroid resistant – no remission after 4
weeks of prednisolone 60mg/m2/day
Presentation
First sign usually facial swelling –
periorbital oedema
 Increasing oedema over days to
weeks
 Lethargy, poor appetite, weakness,
abdominal pain
 May follow an apparent viral URTI
 Haematuria/hypertension unusual
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Differential Diagnoses
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Congestive heart failure
Cirrhosis
Protein losing states
Physical Examination
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Overall inspection
Vital signs
Physical Examination
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Periorbital oedema
Pitting oedema of legs
Scrotal oedema
Sacral oedema
Ascites
Loss of skin creases
Laboratory studies
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Diagnosis based on history and clinical findings
Urine dipstick
24 hour urine collection
U&E
FBC
+/- Hepatitis serology, HIV, serum complement,
varicella serology
Renal US
Others – Antistreptolysin O titres, serum protein
electrophoresis, antinuclear antibodies
Renal biopsy
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Rarely performed in Paediatric cases
Consider if;
Congenital Nephrotic Syndrome
> 8 years at onset
Steroid resistance
Frequent relapses
Significant nephritic manifestations
Treatment
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Prednisolone 60mg/m2/day x 4 weeks, 40mg/m2
alternate days for 4 weeks then STOP
For relapse – prednisolone 60mg/m2/day until
remission, then 40mg/m2 alt doses for 3 doses,
and reduce alt day dose by 10mg/m2 every 3
days until 10mg/m2 alt days – then 5mg/m2 alt
days for three doses then STOP
Consider antithrombotic agents, oral penicillin
VZIG for varicella contacts, aciclovir for varicella
infection
Frequently Relapsing or
Steroid dependent NS
Cyclosporin A
 Tacrolimus
 Cyclophosphamide
 Mycophenolate mofetil
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SRNS
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Should be referred to specialist unit
Full remission not achieved
Aim to reduce proteinuria so not in
nephrotic range
Significant chance of hypertension and
progression to renal failure
If histology shows FSGS – 20-40% chance
of recurrence post transplant
Clinical Features
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SSNS
Toddler, pre-school
No HTN
Mild, intermittent
haematuria
Normal renal function
Excellent prognosis, even
if frequently relapsing
Usually not biopsied
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SRNS
<1 year, > 8 years
HTN common
Persistent haematuria
Renal function often
abnormal
Risk of long term HTN
and renal failure
Usual histology FSGS
Complications
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Infection – typically with Strep pneumoniae
(pneumonia or peritonitis) (oedema &peritoneal
fluid, loss of immunoglobulins,
immunosupression)
Thrombosis – loss of antithrombin III and
proteins S&C in urine, increased procoagulant
factors by liver, increased haematocrit, relative
immobility, steroid therapy
Hypovolemia – shift of fluid from intravascular
space, symptoms – oliguria, abd pain, anorexia,
postural hypotension
Drug toxicity – side effects of steroid treatment,
nephrotoxcity from cyclosporin A or tacrolimus
Congenital Nephrotic Syndrome
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Onset in first 3 months of life
Large placenta – usually 40% of birth weight
Almost always resistant to drug treatment
High morbidity from protein malnutrition & sepsis
Finnish type- most severe, AR
Diffuse mesangial sclerosis – less severe, AR
Denys-Drash syndrome – includes
pseudohermaphroditism and Wilms tumour
FSGS
Secondary congenital nephrotic syndrome – congenital
syphilis
Intensive supportive care – 20% albumin, nutritional
support, early unilateral nephrectomy
Dialysis and transplantation
Glomerulonephritis
Glomerulonephritis
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Refers to a specific set of renal diseases in
which an immunologic mechanism triggers
inflammation and proliferation of
glomerular tissue that result in damage to
the basement membrane, mesangium or
capillary endothelium
Glomerulonephritis
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Sudden onset of haematuria, proteinuria
and red blood cell casts
Often accompanied by hypertension,
oedema and impaired renal function
Represents 10-15% of glomerular disease
Chronic GN may lead to scarring of the
tubulo-interstitial areas of the kidney, with
progressive renal impairment
Pathophysiology
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Lesions are the result of glomerular
deposition or immune complex formation
Kidneys may be enlarged up to 50%
Histological appearance – swelling of
glomerular tufts, infiltration with
polymorpholeucocytes
Immunoflouresence reveals deposition of
immunoglobulins and complement
Causes
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Post infectious – most common, Strep,
viral/fungal/parasitic
Systemic causes – vasculitis, collagen
vascular disease, hypersensitivity, HSP,
Goodpasture, drugs (gold penicillamine)
Renal disease – membranoproliferative
GN, Berger disease, Idiopathic rapidly
progressive glomerulonephritis
Morbidity/Mortality
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Up to 100% of post-streptococcal GN recover
completely
Sporadic cases progress to chronic form in 10%
of children
GN most common cause of chronic renal failure
(25%)
Mortality 0-7%
Male : Female 2:1
Most cases aged 5-15 years
Can occur at any age
Clinical
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Most common- 2-14 year old boy,
presenting with peri-orbital pufffiness after
a strep infection
Urine is dark (‘Coca-Cola’ urine) and
output is reduced
BP may be elevated
Abrupt onset of symptoms
Weakness, fever, abd pain, malaise
Clinical
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Most common- 2-14 year old boy,
presenting with periorbital pufffiness after
a strep infection
Urine is dark (‘Coca-Cola’ urine) and
output is reduced
BP may be elevated
Abrupt onset of symptoms
Weakness, fever, abd pain, malaise
Clinical course
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Latent period of up to 3 weeks after infection(12 weeks postpharyngitis, 2-4 weeks postdermal
inf)
Haematuria universal
Oliguria
Oedema
Headache (sec to hypertension)
SOB or dyspnoea on exertion
Possible flank pain (stretching of renal capsule)
Laboratory studies
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FBC – dilutional anaemia, increased WCC
U&E – ?Elevated urea ± creatinine
Urinalysis – haematuria, Red cell casts present,
24 hour collection helpful
ASOT (increased in 60-80%), anti-DNAse b
ESR ?CRP
Cultures (throat, blood, urine)
Complement (Decreased C3, normal C4)
Other tests
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Radiography – CXR if cough +/haemoptysis
Echo if new murmur/repeated + blood
culture
ANA
Targeted tests
Renal Biopsy
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Acute GN self limited, good prognosis
Significant Renal Impairment, atypical
presentation, family history, massive
proteinuria, nephrotic syndrome
Management
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Treatment mainly supportive
Correct electrolyte abnormalities if present
Post Streptococcal – penicillin therapy
Admission if oliguria and renal failure
Fluid restriction with significant oedema
Complications
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Rare in post-strep GN
Microhaematuria may persist for years
Marked decline in GFR is rare
Chronic renal failure
Nephrotic Syndrome
Acute Post-streptococcal GN
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Onset of reddish-brown (‘Coca-Cola’) urine 1014 days after strep throat or skin infection
Deposition of immune complexes in glomeruli
Treatment mainly supportive
Excellent recovery
Check C3/C4 after recovery – should normalise
Henoch-Schonlein purpura
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70% will have some degree of renal involvement
Usually microscopic haematuria +/- proteinuria
May have relapsing course
Refer if nephritic/nephrotic/sustained
hypertension
Severe cases – steroids, azathioprine
Histologically identical to IgA nephropathy
Follow until urinalysis normal
Accounts for 5-20% of children in ESRF
Summary
Nephrotic Syndrome
Minimal Change Disease most
common, majority steroid sensitive,
peri-orbital oedema most common
presenting feature
 Glomerulonephritis
Presents with haematuria, usually
post infectious in children, mainly self
limiting, supportive treatment
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