Nephrosis and

Nephritis

1) Nephrotic Syndrome
2) Glomerulonephritis

Nephrotic
Syndrome

Nephrotic Syndrome

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

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

Group A beta-haemolytic strep

Syphilis
Malaria
TB
Viral infections (varicella, HBV, HIV-1,
infectious mononucleosis)

Histological Classification

Minimal-change nephrotic syndrome

(MCNS) = 84.5%
Focal Segmental glomerulosclerosis
(FSGS) = 9.5%
Mesangial proliferation = 2.5%
Membranous nephropathy & others
= 3.5%

Therapeutic Classification

Steroid sensitive (85-90%)

Steroid resistant (10-15%)
Steroid dependent
Frequently relapsing

Pathophysiology

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

Definitions

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/m 2/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

Differential Diagnoses

Congestive heart failure

Cirrhosis
Protein losing states

Physical Examination

Overall inspection
Vital signs
Physical Examination

Periorbital oedema
Pitting oedema of legs
Scrotal oedema
Sacral oedema
Ascites
Loss of skin creases

Laboratory studies

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

Rarely performed in Paediatric cases

Consider if;
Congenital Nephrotic Syndrome
> 8 years at onset
Steroid resistance
Frequent relapses
Significant nephritic manifestations

Treatment

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/m 2
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

SRNS

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

SSNS
Toddler, pre-school
No HTN
Mild, intermittent
haematuria
Normal renal function
Excellent prognosis,
even if frequently
relapsing
Usually not biopsied

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

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

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

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

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

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

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

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

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

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

Latent period of up to 3 weeks after

infection(1-2 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

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

Radiography CXR if cough +/haemoptysis

Echo if new murmur/repeated +
blood culture
ANA
Targeted tests

Renal Biopsy

Acute GN self limited, good prognosis

Significant Renal Impairment,

atypical presentation, family history,
massive proteinuria, nephrotic
syndrome

Management

Treatment mainly supportive

Correct electrolyte abnormalities if
present
Post Streptococcal penicillin therapy
Admission if oliguria and renal failure
Fluid restriction with significant
oedema

Complications

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

Onset of reddish-brown (Coca-Cola) urine

10-14 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

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