proteinurea
10% of children aged 8-12 years have +ve test for Protienurea.
Ways of detection of Protienurea.
1-Dipstick, qualitative assessment of protein excretion, primarily 
for albumin and less sensitive for others types of protein(LMW,
Bense Jones , gamma globulin),trase(10-20mg/dl), +=30, ++(100),
+++=(300) , ++++=1000-2000mg/dl.
False +ve 1-grosse haemeturia
2-contamination with antiseptic
3- urine PH greater than 7
4- phenozopyridne medication
5- high concentrated urine(sp.gravity more than 1.015)
False –ve 1- diluted urine(sp.gravity less than 1.005)
2- other than albumin
2-Timed 12-24H urine collection for protein
Normally 150mg/day, or 4mg/m2/day
Abnormal=4-40mg/m2/hr
Nephrotic range more than 3.5g/day or more than
40mg/m2/hr
3- URINARY PROTIE/ URINARY CREATINNE
(upro/ucre)
Normally less than 0.5 in child less than 2year and less
than 0.2 in child more than 2year
More than 3 suggest nephrotic range.
Nephrotic syndrome
Definition
prevalense 2-3/100000 
Disease of children (15 fold than adult)

1.proteinuria above 40 mg/m²/hr(or 1g/kg/24hr)or urinary protein 
(mg/dl)/creatinine(mg/dl)ratio of 2.0 or more ;alternative units-ratio
more than 0.2mg/micromole
2. Hypoalbuminamia(serum albumin less than 25g/l
3.Hypercholesterolemia(serum cholesterol over 
200mg/dl,5.25mmol/l
4.Oedema
The primary abnormality is protein urea .others features are 
secondary to this, others chara .findings include
.Hypocalcaemia(ionized fraction normal),below 9.0mg/dl
.Hyponatremia(below 135mmol/l
.Hypercoagulabity(decrease partial thromboplastin time(PTT)
Etiology
90% Idiopathic,10%secondary(related to glomerular diseases like 
membranous nephropathy, membranoprolefretive)
85%minimal change disease nephrotic syndrome(MCNS)
Most common type ,affect younger children (2-5),and more in 
boys(until the puberty),it is thought to be due to defective electrostatic
glomerular barrier (due to circulating lymphokine).
An associated defect is proliferation of a T- cell subclass.MCNS 
characteristically shows fusion of epithelial foot process on electron
microscopy
Clinically , hypertension and haemeturia occur in 10% and in about 
95%steroid responder
10%Focal segmental G.sclerosis ,histolegically,there is mesangial 
proliferation, increase in matrices, and segmental sclerosis,20% steroid
responder and may lead to end stage renal failure
5%Mesangial proliferative deffuse mesangial l cell proliferation, 
increase in matrice, 50% steroid responder .
Pathpphysiology
Increase permeability of glomerular capillary wall lead to massive 
protein urea and hypoalbuminemia.
The cause still unknown,in MGNS , there is possiple T- cell defect,
In focal segmental sclerosis, plasma factor, perhaps prodused by 
lymphokines may responsible for increase in capillary wall
permeability
protein urea→hypoalbumin→↓oncotic pressure→shifting of fluid 
from intravascular spase to the interstitial
compartment→↓↓intravascular volume →↓renal
perfution→activate Renin-Angiotensen-Aldosteron
system→stimulate tubuler reabsorption of NA+ alsoADH lead to
reabsorption of water →Odem
This theory not apply to all patients with nephrotic syndrome, 
however, because some patients actually have increase
intravascular volume with diminished levels of rennin and
aldosteron.Therefore, other factors, including primary renal
avidity for sodium and water, may be involved in the formation
of odema in some patients with nephrotic syndrome.
Hyperlipidemia(cholesterol and trigyceride) is due to
1- Hypoalbuminamia may stimulate hepatic synthesis of 
lipoprotein
2- loss of lipoprotein lipase in urine which is responsible for 
degradation of lipoptotien.
Minimal change disease nephrotic
syndrome(MCNS)
Clinical feature
Most common age (2-6),reported as early as 6months of age
The initial episode and subsequent relpse may flow minor 
infection,occusionaly related to insect bite.
Mild edema noted around the eye and then to lower extremity ,may 
be misdiagnosed as allergic disorders. with time edema become
generalized with ascitis,pleural effusion and genital odema
Anorexia, irritability,abdominal pain,diarrhea are common
Hypertension and grosse hematuria are uncommon
D.DX
Hepatic failure, congestive heart failure, acute or chronic GN, 
protein malnutrition , protein loosing enteropathy
Diagnosis
Any child with NS should probably have the following 
tests
URINE

1-proteinin urine 3+ or 4+(1+=10-
20mg/dl,2+=100mg/dl,3+=300mg/dl,4+=1000-2000mg/dl)or
proteinuria above 40 mg/m²/hr(or 1g/kg/24hr)or urinary
protein (mg/dl)/creatinine(mg/dl)ratio of 2.0 or more
;alternative units-ratio more than 0.2mg/micromole
2- cellular cast which do not to occur in INS but may well 
occur in other glomerlonephropathies(note that halyine or
waxy casts are common in INS
3- micro .RBC in 10-20%. 
BLOOD
1- Urea , creatinin and electrolytes(renal function usually
normal in INS(10-20%increase in BUN); may be abnormal in
other glomerlonephropathies
2- Albumin(less than2.5g/dl) and total serum protien
3- increase Serum cholesterol and triglyceride
4 Serum complement level C3,C4(low with msangial
proliferative ,SLE., normal in INS)
5- Hepatitis B and C serology (Hep B is associated with
membranous nephritis, Hep C is associated with msangial
proliferative.
Renal biopsy
not required in most patients, and should be reserved for 
those very atypical feature. There is probably NO indication
for biopsy before commencing non-steroid agents if the child
completely responsive to predisolone (protein urea absent in
the past 3 days).so indicated in the following
1- Age before 1year and above 8years
2- Macroscopically hematuria
3- Persistent hypertension and

microscopically hematuria
4-Abnormal levels of complements
5- Elevated serum creatinin level

Definitions in NS
Remission=urinary protein excretion less than 4mg/ 
m²/hour or trace of protein in urine dipstick, or urinary
protein (mg/dl)/creatinine(mg/dl)ratio of0.2 mg/dl for 3
consecutive days
Relapse=recurrence of protein urea defined in INS 3-
4+dipstick +edema.
Frequent relapser=2 or more relapse in the first 6months 
of initial response OR more than 4 relapse in 12months
Corticosteroid dependence=2 consecutive relapse while 
on steroid (every other day) or within 2 weeks of ceasing
steroid
Corticosteroid resistance =failed response after 8weeks of 
2mg/kg/day
Treatment (supportive )
mild to moderate edema may be managed as outpatients , lowsodium diet , oral diuretics????
severe symptomatic edema, including large pleural effusions,
ascites, or severe genital edema, should be hospitalized. In
addition to sodium restriction, fluid restriction may be necessary
if the child is hyponatremic
. A swollen scrotum may be elevated with pillows to enhance the
removal of fluid by gravity. Diuresis may be augmented by
administration of furosemide (1–2 mg/kg/dose IV q 12 hr).
IV administration of 25% human albumin (0.5 g/kg/dose q
6–12 hr administered over 1–2 hr) followed by furosemide
(1–2 mg/kg/dose IV) is often necessary when fluid restriction
and parenteral diuretics are not effective. Such therapy
mandates close monitoring of volume status, serum
electrolyte balance, and renal function. Symptomatic volume
overload, with hypertension and heart failure, is a potential
complication of parenteral albumin therapy, particularly with
rapid infusions.
Treatment(specific)
In children with presumed MCNS, prednisone should be administered (after
confirming a negative PPD test and administering the polyvalent pneumococcal
vaccine) at a dose of 60 mg/m2/day (maximum daily dose, 80 mg) in a single
daily dose for 4-6 consecutive wk. An initial 6-wk course of daily steroid
treatment leads to a significantly lower relapse rate than previously
recommended shorter courses of daily therapy. About 80-90% of children
respond to steroid therapy (clinical remission, diuresis, and urine trace or
negative for protein for 3 consecutive days) within 3 wk. The vast majority of
children who respond to prednisone therapy do so within the first 5 wk of
treatment.
After the initial 6-wk course, the prednisone dose should be tapered to
40 mg/m2/day given every other day as a single daily dose for at least 4 wk. The
alternate-day dose is then slowly tapered and discontinued over the next 12 mo. There is evidence that both an increased dose of steroids and a prolonged
duration of therapy are important factors in reducing the risk of relapse. While
planning the duration of steroid therapy, the side effects of prolonged
corticosteroid administration must be kept in mind.
Many children with nephrotic syndrome experience at least 1 relapse
(3-4+ proteinuria plus edema). Although relapse rates of 60-80% have
been noted in the past, the relapse rate in children treated with longer
initial steroid courses may be as low as 30-40%.
Relapses should be treated with 60 mg/m2/day (80 mg daily max) in a
single am dose until the child enters remission (urine trace or negative
for protein for 3 consecutive days). The prednisone dose is then
changed to alternate-day dosing as noted with initial therapy, and
gradually tapered over 4-8 wk.
2-Other agents,cytotoxic
drugs(CLAIM
C cyclophosphamide(CPA:2-3mg/kg for 8-12weeks),Chlorambucil
0.2mg/kg for 8-12 weeks), Cyclosporine(CSA:2.5mg/kg12hourly for
12months
L levamisole(2.5mg/kg daily for 6-12 months)
A angiotensin-converting enzyme ACE inhibitors
I immunization with pnuemoccocal vaccine
M mycopgenolate mofetil 25mg/kg /day for 1year
CPA has significant side effect ,short term=bone morrow
suppretion.risk of viral infections such as varicella,measles)long term
(gonadal toxicity and risk of malignancy)
CAS can cause nephrotoxicoty, hypertention,gingival hypertrophy and
hirsutism
Levemisole cause enhanced celluler immune response in certain 
conditionswith depressed immune function,and may help to
maintain remission in steroid-dependent INS(neutropenia,rarly
vasculitis,liver toxicity,convulsion )
ACE inhibitor reduce glomerular hyperfilteration (hypotention and 
cough)
Immunization,heptavalent conjugate(7vPCV) in children less than 
5years and polysaccharide pnuemoccocal vaccine (PPV23) 5YEARS
AND OLDER
mycopgenolate mofetil used in lopus type
ALL the above medications are indicated in the following 
1- steroid resistant type 
2- steroid dependent type(only if side effect are unacceptable)
3- frequent relapse with hypertension or thrombosis
4- unacceptable steroid side effect(weight gain, cushnoid facies 
3- Antibiotics
Some unite treat all episodes of relaps with
prophylactic daily penicillin to ovoid
pnuemoccocal infection. Others not, some
use hird generation cephalosporin ,however
the use of prophylactic antibiotic during
relapse remain controversial
4- Immunization
Live viral vaccine should be avoided in patient
taking steroid or other immune suppressive drug.
pnuemoccocal vaccine is recommended and
annual influenza vaccine.
5- Hypertension
Minority, treated by nifedipine and beta blocker
6- Diet
No added salt, no fluid restriction unless in very edematous
and diuretics is required ,high biological value protein.
8- In hospital management
Fluid balance chart, twice daily weight, 4-horly chart of vital sings.
9- Activity
No need for bed rest or restriction of activity.
Complications of NS
1- Infection
More with encapsulated bacteria(pnuemoccocal, haemphilus ) 
including spontaneous bacterial peritonitis (SBP) , cellulites,
UTI,pneumonia due to many factors
•urinary loss of immunoglobulin
•loss of B factor of alternate activation path.
•loss of transferring
•alter T- cell function
•steroid and other immune suppressive therapy
•mechanical factors such as edema and ascitis
•malnutrition
The occurrence of (SBP)is 2-6%and this risk is further increased by 
decrease mesenteric blood flow and increase coagulability causing
micro infarction
The (SBP) need high index of suspicion because the clinical signs 
some times are masked by the steroid (blood culture, peritoneal fluid
culture then prompt antibiotic)
2- Thromboembolism
NS associated with Hypercoagulabity (2-5%) state due to
Due to increase prothrombotic activity(fibrinogen, 
thrombocytosis, haemoconcetration and relative
immobilization ) and decrease fibrnolytic factor(loss of
antithombin 111, and protie C, S), prophlyctic anticoagulant
not recominded unless they have previous thromboemboliv
event.
Over use of diuretics, and use of indwelling catheter should 
be restricted.
Prognosis
Majority of child with steroid responsive NS had repeated 
relapse with time, decrease relapse specially if not getting
relapse in the 1st 6months
steroid responsive NS not lead to chronic renal failure, and not 
hereditary, normal sterility in absence of prolonged use of
cyclophosphomide)
child during remission no need for testing of Protienurea.
Steroid resistant NS
poor prognosis end stage renal 
failure dialysis and renal transplant(30-50% getting the same
disease)
Secondary NS
10%
1-drugs(pencillamine, gold
2- membranoprolefretive NS
3-PSGN, LOPUS, HSP
4- infection malaria, Hepatitis B,C, HIV
5- Malignancy H. lymphoma.
Congenital NS
In the 1st 3month most common type
Finnish type autosomal recessive ,increase alpha feto 
protein, large placenta, marked edema, prematurely, RDA,
separation of cranial suture
Lead to end stage renal disease, no value of steroid or 
cytotoxic
ACE inhibitor, endomethacine, unilateral nephrectomy
Other form is due to infection(TORCH). 