16.Nephrotic Syndrome

8/12/2019 16.Nephrotic Syndrome

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NEPHROTIC SYNDROME


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Introduction

Develops when an abnormality of glomerular

permeability results in heavy proteinuria

(>3.5g/24hr), hypoalbuminaemia (


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Cont

Minimal changes disease (MCNS) Male > female (3:2)

Most cases, onset between ages 2-6 years withmedian age at presentation of 3 years

Etiology remain incompletely defined

There appears to be an abnormality of thenegatively charged residues in the glomerularbasement membrane, which normally limit thefiltration of anion plasma protein (e.g. albumin)

Typically responds to corticosteroids therapy &

usually associated with a favourable long-termoutcome

At least 70% of patient will experience a chronic,relapsing-remitting course


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Cont

Heterogeneous group of conditions, including

focal segment glomerulosclerosis (FSGS) &

mesangiocapillary glomerulonephritis (MCGN)

account for remaining 20% of cases of NS inchildhood

Compared to MCNS, these disease tend to present

in older children

Majority of patient do not enter remission withstandard initial corticosteroid therapy

Their prognosis is correspondingly poorer


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Cont

Majority of cases respond to empirical

corticosteroid therapy without the

underlying histological diagnosis being

confirmed

Steroid sensitive nephrotic syndrome

(SSNS) was adopted for this group


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Cont

Histological diagnosis in children

presenting with NS & outcome of

corticosteroid therapy

Nephrotic children

100

Minimal change

80

FSGS

10

MCGN & Others

10

Steroid sensitive 75

Steroid resistant 5

Steroid sensitive 2

Steroid resistant 8

Steroid sensitive 2

Steroid resistant 8


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Clinical features & diagnosis

Recognition of illness & the formulation

of a diagnosis

Usual presenting symptom is edema

important to exclude other condition

Edema initially present in a peri-orbital

distribution, which particularly noticeable

in the morning after the child has been

recumbent overnight


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Differential diagnosis of generalized

edema

Renal condition

Nephrotic syndrome

Acute nephritic syndrome

Acute renal failure

Non-renal condition

Severe cardiac failure Chronic liver disease

Protein-losing enteropathy


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As further ECF accumulatesedemadevelops in the dependent areas of lower limb& genitals

In more advanced cases, fluid accumulation inthe serous body cavitiespleural effusion &ascites

Onset of illness is often preceded by a history

of viral URTI & the development of edemamay be accompanied by general malaise &irritability


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Clinical assessment of NS

History of presenting illness Age

Duration & progress of symptoms

Fluid intake

Urine output Adequate/oliguric

Antecedent illness Often viral URTI in SSNS

Past medical history History of atopic disease

Present in 30-60% of cases of SSNS Previous vericella infection

Risk of severe infection in non-immune patients afterimmunosuppression


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Drug history Including immunization history

Family history

History of NS ~3% of NS patient have an affected sibling:

histological type & steroid responsiveness areusually similar within family

Chronic renal failure May suggest poor prognosis if CRF was

preceded by SRNS


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Cont

Examination

Height & weight

BP

Pulsecapillary refill time

Plural effusion

Ascites

edema


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Acute complication Hypovolaemia

Infection

ThrombosisChronic complication

Age 12 years

Persistent hypertension

Gross haematuria Renal impairment

Plasma C3


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1stline investigation in NS

Patients presenting with typical features ofuncomplicated NS require only limited initialinvestigation Urine dipstick analysis (protein, blood)

Early morning urine protein/creatinine ratio

Urine microscopy and culture

Plasma albumin, creatinine and electrolytes

FBC

Complement C3 & C4 levels

Varicella zosterantibody titres

Hepatitis serology (Type B & C)


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Atypical features

Considered in SSNS & suggest the possibility

of an alternative diagnosis (which is less likely

to respond to corticosteroid therapy)

Principal atypical features Age 12 years

Persistent hypertension

Persistent renal impairment

Gross haematuria

Low plasma C3 concentration


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2ndline investigation in NS

Atypical features warrant further

investigation & should be referred to a

paediatric nephrologists

Antistreptolysin O titre (ASOT)

Antinuclear antibodies (ANA)

Anti-ds DNA antibodies


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General management

General management

Fluid balance Blood pressuremonitoring

Prophylaxis

Information for

parentsMobilization & Diet


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Fluid balance

Salt-restricted diet

Daily weight measurement

If no hypovolaemia:

-Advise for modestly restricted fluid intake

-Diureticse.g frusemide 2mg/kg per 24h

may be combined with spironolactone 2mg/kg

per 24h


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Blood pressure monitoring

Children with MCNS/SSNS usually

normotensive

Hypotension-sign of hypovolaemia

Hypertension requires careful evaluation

If necessary, oral nifedipine(200g/kg per

dose 3 times a day) may be used as an initial

antihypertensive treatment.


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Prophylactic antibiotics

Other than albumin, other important plasma proteins

are lost in urine of nephrotic children.

Urinary loss of immunoglobulinsand complement

components leads to susceptibility to bacterial

infection.

e.g peritonitis (Streptococcus pneumoniae)

septicemia (streptococci and Gram-negative organism)

cellulitis (staphylococci)

Commonly, prophylactic antibiotics prescribed (oralphenoxymethylpenicillin 12.5mg/kg per dose twice

daily)


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Mobilization and Diet

Mobilization

To prevent venous thrombosis

Encourage patient to mobilize as normal and

avoid bed rest.

Diet

No specific dietary advice

Salt restriction

Healthy eating


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Information for parents

Explain the diagnosis

Management plan

Importance of compliance with medication

Adverse effect of medication

Need of outpatient follow-up

* In patient hospitalized in the first nephrotic episodes,educate parents how to perform dipstick testto

enable monitoring for relapse after discharge


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Approach to an adult patient with

Nephrotic Syndrome

1.Confirm diagnosis

2.Search for 2causes/1renal disease

i. thorough history and physical examination

ii. further laboratory investigations

iii. renal biopsy

3.Assessment of

i. renal function

ii. complications

4.Management

i. render patient asymptomatic (relief of edema)ii. treat underlying cause

iii. maintain normal renal function

iv. treat complications


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i. Relief of edema-low salt diet(50-100mmol sodium/day)

-normal protein intake

-Diuretics-oralor iv

ii. Treat underlying cause1renal disease-steroid

-cytotoxics eg.cyclophosphamide2causes-eg treat diabetes mellitus, Hep B carrier,

myeloma


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iii. Treat complications of Nephrotic

Syndrome

-succeptibility to infection

-thrombosis-hyperlipidaemia

-loss of binding proteins in urine

-protein malnutrition

-acute renal failure


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Specific management

1. For initial episode of NS

Prednisolone 60 mg/m, 3x daily followed

by prednisolone 40 mg/m on alternatedays for 14 doses over 28 days


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2. For relapsing episode prednisolone 60 mg/m2, 3x daily until remission

followed by prednisolone 40 mg/m on alternate

days for 14 doses over 28 days

only use for the first 2 relapses about 25% of relapses remit spontaneously, but

need to be treated after 35 days to:

minimize steroid use

avoid hypoalbuminaemia allow possibility of spontaneous remission


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Standard definitions in monitoring of SSNS

Remissionurine protein dipstick (Albustix) reading 0 or trace for 3consecutive days

Relapse

Albustix reading 2+ or more for 3 consecutive days, havingpreviously been in remission

Frequently relapsing NS

2 relapses within 6 months of initial response or 4 relapseswithin any 12 months period

Steroid dependant NS

2 consecutive relapses occurring during corticosteroid treatmentor within 14 days after its cessation


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3. For frequent relapse

maintenance prednisolone: 0.1-0.5 mg/kg

on alternate days up to 12 months

4. If patient develops frequent relapses

with steroid dependency: refer to a

nephrologist

Sid ff f d i l


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Side effect of prednisolone

(corticosteroid)

Susceptibility to infection

Mood & behaviouraldisturbance

Increase appetite

Weight gain & obesity Cushingoid appearance

Acne

Hirsutism

Cutaneous striae Posterior subcapsular

cataracts

Hypertension

Growth suppression

Pubertal delay

Adrenal suppression

Impaired glucosemetabolism

Dyspepsia & pepticulceration

Acute pancreatitis Osteoporosis

Avascular osteonecrosis


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Subsequent management

For patient on maintenance prednisolone

Follow-up every 3 months to check BP &

growth (pubertal status, bone age graft) Cataract assessment annually

A steroid warning card should be given

Alt ti i d l t


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Alternative immunomodulatory

therapy for NS

Indication for alternative immunomodulatory

therapy in steroid-sensitivity NS

Relapse while taking prednisolone >1 mg/kg on

alternate days Relapse while taking prednisolone >0.5 mg/kg on

alternate days + 1 of the following

Unacceptable adverse effect of corticosteroid therapy

High risk of adverse steroid effects (e.g. boys approaching

puberty, diabetic children)

Unusually severe relapses (hypovolaemia, thrombosis,

severe sepsis, acute renal failure


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Immunomodulatory therapy

1. Levamisole

Use after remission with prednisolone: 2.5

mg/kg on alternate days

Then tapering & discontinue

MOA: not fully understood

Advantage

Safe Very infrequently case neutropaenia


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2. Alkylating agents

Cyclophosphamide: use after remission with

prednisolone 3 mg/kg daily dose for 8 weeks

course

Advantage:

induce long term remission/reduction of relapse frequency

Disadvantage:

Bone marrow suppression

Risk of infection

Gonadal toxicity for male patient


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3. Cyclosporin To control frequent relapse recurring after previous course of

cyclophosphamide. OR

Pt. at high risk of cyclophosphamide side effect (e.g. peri-pubertal boys)

Give after remission with prednisolone: 2.5 mg/kg per dosetwice a day then discontinue when achieve therapeutic level

Disadvantage

Only effective in maintaining remission during period ofadministration. (dyscontinue relapse)

Chronic nephrotoxicity: renal biopsy should be done after 18-24

months of therapy Tremor

Hypertrichosis

Gingival hypertrophy

hypertension


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Long-term prognosis

In childhoodvery good

20% of pediatric patient: will have relapses onteenage years

5 years remission 20% of patient of relapsesubsequently

After 10 years remission, risk of relapsedecrease

Mortality rate 1-7.2% (mostly in 1960-1970)largely d/t acute complication of sepsis &vascular thrombosis


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Diagnosis

Nephrotic syndrome is a clinical syndrome of massive proteinuria defined by

1. Oedema

2. Hypoalbuminaemia of < 25g/l

3. Proteinuria > 40 mg/m2/hour ( > 1g/m2/day ) OR an early morning urine protein

creatinine index of > 200 mg/mmol ( > 3.5 mg/mg ) 4. Hypercholesterolaemia is not needed in definition

The main cause of nephrotic syndrome in children is primary or otherwise known

as

idiopathic nephrotic syndrome when the actual cause of the nephrotic syndrome is

unknown. The treatment for nephrotic syndrome caused by other diseases

example post streptococcal glomerulonephritis or systemic lupus erythematosus follows that for

the

treatment of the primary renal/systemic disorder.


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Investigations at initial presentation

1. Full blood count

2. Renal profile - urea, electrolyte, creatinine

3. Serum albumin

4. Urinalysis and Culture

5. Quantification for urinary protein excretion (spot urine protein

creatinine ratio or 24

hour urine protein)

Other investigations if the clinical features are atypical / presence of poor

prognostic

features

1. Antinuclear factor / anti ds DNA

2. Serum complement (C3, C4) level

3. ASOT

4. Others as indicated


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Renal biopsy

Not indicated for idiopathic nephrotic syndrome in children prior to

starting corticosteroid

therapy.

Main indication is steroid resistant nephrotic syndrome defined as

failure to achieve

remission despite 4 weeks of adequate corticosteroid therapy.

Other indications would depend on presence of atypical features and

features to

suggest other renal diseases e.g. persistent hypertension, gross

haematuria and shall be left to the discretion of the attending paediatrician in consultation

with the

paediatric nephrologist.


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Management

A. Management of the oedematous state

Bed rest

This is not required and usually not practical unless the child has

gross oedema. Diet

A normal protein diet with adequate calories is recommended.

No added salt to the diet during the oedematous state.

Antibiotics.

Penicillin V 125 mg BD (1-5 years old); 250 mg BD (6-12 years

old) 500 mg BD (>12

years) is recommended during relapse particularly with gross

oedema.


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o Human albumin (20-25%) at 0.51.0 g/kg can be used in symptomatic

grossly oedematous states together with intravenous frusemide at 1-2

mg/kg

to produce a diuresis. Caution: fluid overload and pulmonary oedema

with

salt poor albumin infusion. Urine output and blood pressure should beclosely

monitored.

o Human albumin at 0.51.0 g/kg of 5%, 20% or 25% (whichever is

available)

over one hour in those suspected to have hypovolaemia/underfilledstate. Do

not give frusemide in this instant


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Fluid status

Carefully assess the haemodynamic status. Check for signs and

symptoms which

may indicate underfillingabdominal pain, cold peripheries, tachycardia

and poor

pulse volume, low blood pressure or overfilling e.g. basal lungcrepitations and

rhonchi, hypertension.

Fluid restriction - not usually recommended except in chronic

oedematous

states. o Diuretics. e.g. frusemide is not usually necessary in steroid responsive

nephrotic syndrome but if required should be used with caution as it

can precipitate hypovolaemia.


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B. Management of the complications of nephrotic syndrome

Hypovolaemia.

Clinical features: abdominal pain, cold peripheries, poor pulse volume,

hypotension, and haemoconcentration.

Treatment: infuse salt poor albumin at 0.5 to 1.0 g/kg/dose over one hour. If salt

poor albumin is not available, other volume expanders like 5% albumin, plasma protein derivatives or human plasma can be used.

Primary Peritonitis

Clinical features: fever, abdominal pain in children with frank nephrotic syndrome.

Investigations: Blood culture, peritoneal fluid culture (not usually done)

Treatment: parenteral penicillin and a third generation cephalosporin

Thrombosis

Thorough investigation and adequate treatment with anticoagulation is usually

needed.


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C. General advice

Inform regarding high probability (85-95%) of relapse.

Home urine albumin monitoring. Urine dipstix testing of the first

urine specimen

in the morning daily. Parents are advised to consult the doctor ifalbuminuria > 2+

for 3 consecutive days.

Immunocompromised status


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o The parents and children should be advised and cautioned

about contact

with chickenpox and measles, and if exposed should be treated

like any

immunocompromised child.

Immunisation.

While the child is on corticosteroid treatment and within 6 weeks

after its

cessation, only killed vaccines may safely be administered to the

child. Live vaccines can be administered 6 weeks after cessation of

corticosteroid therapy.


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Acute Adrenal Crisis

This may be seen in children who have

been on long term corticosteroid

therapy (equivalent to 18 mg/m2 of

cortisone daily) when they undergo

situations of stress.

Prevention and treatment: corticosteroids

(hydrocortisone) given in 3

divided doses at 2-4 mg/kg/dose.


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D. Corticosteroids

Corticosteroids is effective in inducing remission of nephrotic syndrome but the

most

optimal dose and duration is yet to be resolved although it has been found that

longer

duration results in more prolonged remission.

Prednisolone dosage at:

* 60 mg / m2 / day ( maximum 80 mg / day ) for 4 weeks

* followed by 40 mg / m2 / EOD (maximum 60 mg) for 4 weeks.

* then reduce prednisolone dose by 25% monthly over next 4 months.

90% of children will achieve remission defined as urine dipstix is trace or nil for 3

consecutive day within 28 days, many within 7 - 14 days. Steroid resistance isdefined

as failure to achieve response to an initial 4 weeks treatment with prednisolone 60

mg/m2/day and such case should be referred to a nephrologist for a renal biopsy.


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Treatment of relapses

The majority of children with nephrotic syndrome will relapse.

A relapse is defined by urine albumin excretion > 40 mg / m2 / hour or

urine

dipstix of 2+ or more for 3 consecutive days.

Treatment - Prednisolone 60 mg/m2 /day until remission then 40 mg /m2/EOD for 4

weeks and off.

Breakthrough proteinuria may occur with intercurrent infection and

usually does not

require prednisolone if the child has no edema, remains well and theproteinuria resolves

with resolution of the infection. If proteinuria persists, treat as relapse.


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Management of frequent relapses

Frequent relapses = 2 or more relapses within 6 months of initial

response or 4 or more

relapses within any 12 month period.

Treatment Prednisolone 60 mg / m2 / day till urine albumin nil/trace for 3

days, then 40 mg / m2 /

alternate mornings for 4 weeks. Taper prednisolone dose every 2

weeks and keep on

as low alternate day dose as possible for 6 months. Should achild relapse while on low

dose alternate day prednisolone, the child should be re-induced

as for a relapse.


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Management of steroid dependent nephrotic syndrome

Steroid dependence = 2 consecutive relapses occurring during

the period of steroid

`taper or within 14 days of its cessation.

Treatment If the child is not steroid toxic, re-induce with steroids and

maintain on as low a dose of

alternate day prednisolone as possible. If the child is steroid toxic

(short stature, striae,

cataracts, severe cushingoid features) considercyclophosphamide therapy


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E. Cyclophosphamide therapy

This is indicated for the treatment of steroid dependent nephrotic

syndrome with signs of

steroid toxicity and should be started when the child is in

remission following induction

with corticosteroids.

Dose: 2-3 mg/kg/day for 8-12 weeks

Monitoring: FBC and Urine FEME two weekly.

.


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Relapses post cyclophosphamide

Relapses after a course of cyclophosphamide is

treated as for relapses after the initial

diagnosis of nephrotic syndrome if the child does not

exhibit any further signs of steroid

toxicity.

Should the relapse occur soon after a course of

cyclophosphamide when the child is still

steroid toxic, or the child again becomes steroid toxic

after multiple relapses, then a

paediatric nephrology opinion should be sought


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Steroid resistant nephrotic syndrome / chronically nephrotic child

Refer for renal biopsy. Specific treatment will depend on the

histopathology.

General management

Control of edema - (a) Restriction of dietary sodium. (b) Diuretic e.g. Frusemide, Spironolactone.

ACE inhibitor e.g. captopril to reduce proteinuria

Control of hypertension.

Penicillin prophylaxis.

Monitor renal function.


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Nephrotic Syndrome

Case Presentation


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History

Identification data

Name : Sakimmi Latiff

Age : 21 years oldRace : Malay

Sex : Male

Occupation : Laborer

Address : Kubang KerianDate of admission : 12-09-2006

Date of clerking : 14-09-2006

Informant : Patients himself


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Chief complaint

Facial puffiness and bilateral limbs oedema 2weeks prior to admission.


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History of presenting illness

Patient was apparently well until 4 weeks ago when he started tohave facial puffiness and bilateral leg swelling.

He sought medical consultation at HUSM. After the investigationshave done, he was told to have renal problem by doctors.Medication was prescribed and he was required to follow up atHUSM.

His symptoms resolved after taking the medication. However he

defaulted the follow up at HUSM


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About 2 weeks ago, his symptoms reccured.

He discovered the limbs edema after waking up in themorning while the facial edema was noted by his mother

at the time.

The swelling was gradually increased in size especiallywhen he was walking. It swelled in the morning and

subsided in the evening initially but later the swelling

appeared to persist for the whole day. However it was

painless.


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He also complaint of abdominal swelling 2days after the

legs edema and facial puffiness.

On further questioning, he was known to take pil

kuda(metamphetamine pill) previously but stop 1 year

ago.


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He denied of any upper respiratory tract or urinary tract

infection like fever, sore throat, pharingitis or dysuria.

There was no joint pain, muscle ache, rashes, oral

thrush,loin pain or haematuria.

There was no paroxysmal nocturnal dyspnea, no

orthopnea, no palpitation, no chest pain.

He had no history of Diabetes Mellitus or hypertension.No previous history of blood transfusion or other drug

abuse noted.


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Past medical and surgical history-nil of significant

Social history

- no smoking

- taking alcohol ( Beer once per week )

Drug history

- pill kuda about 1 years ago

Food history

- no allergic to any food


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Family history

He is 5thchild out of 11 siblings.

Father not working. His mother is factory

worker. No family history of similar

illness.


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Physical examination

General examination:

Inspection

My patient is a medium bulid malaymale, lying comfortable with one pillow. He isalert, conscious and well orientated with time,place and person. He is not in pain andrespiratory distress. His nutritional and

hydrational status is adequate. There is nogross deformity and abnormal movement canbe found. Bilateral leg edema and facialpuffiness was noted.


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Vital sign :

B/P : 120/80mmHg

H/R : 70 bpm

Temperature : 37.5C

Respiratory rate : 15 per minute


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Hand- palm is warm

- No pallor

- No palmar erythema

- No peripheral cyanosis

- No clubbing

- No leuconychia

- No half and half nail- No scar of needle injection in both fore armand arm


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Head

- Conjunctiva is pink

- No yellowish discoloration at sclera

- Moist tongue

- No central cyanosis

- No ureamic fetor


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Forearm and arm

- No scratch mark

- No bruising

- No skin pigmentation

No flapping tremor


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Neck

-No elevation of JVP

Lower limp

-bilateral pitting edema until knee level

Lymph nodes does not palpable


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Gastrointestinal system :

- Hepatomegaly :liver span: 14cm

Spleenomegy :Spleen just palpable

Dullness at Traubes

space

- Ascites : Shifting dullnes

positives


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Cardiorespiratory system

Inspection:

- No spider naevi

- No gynaecomastia-Jugular venous pulse not elevated

Palpation

Apex beat at 5thintercostal space, mid clavicular line


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Auscultation:

- S1S2 present, no murmur

- Vesicular breath sound at both lung

- Percussion nodes are resonance

- No additional breath sound

eg.Crepitation

Summary


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Summary

Patient was a 21 years old, maleadmitted due to facial puffiness andbilateral leg swelling 2 weeks prior to

admission.On physical examination, patient was

noted to have bilateral leg swelling, facialpuffiness, hepatomegaly, splenomegaly

and ascites.

Provisional diagnosis


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Provisional diagnosis

Nephrotic syndrome secondary toinfection

-Point towards : bilateral leg swelling

facial puffinessascites

hepatosplenomegaly

-Point against : no fever

no jaundice


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Investigation


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Investigation

Full blood count- To assess general condition of patient, look for any anemia in

chronic disease or infection

- Results:

- WBC- 12.5x109/L (increase)

- Hb- 10.89/L (decrease)

- RBC- 3.94x1012/L (decrease)

- MCV- 82.5fl (normal)

- MCH- 27.4pg (normal)

- MCHC-20mmol/L (normal)

- Platelet- 375x109/L (normal)

- Lymphocytes- 5.4x109/L (increase)- Neutrophils- 5.7x 109/L (normal)

- Anemic and suggestive of virus disease


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BUSE

- BUSE is to assess electrolyte imbalance

- Results:

- Creatinine- 75mmol/L (normal)- Urea -5.8mmol/L (normal)

- Na-136 mmol/L (normal)

- K- 4.2mmol/L (normal)

- Calcium- 1.92 mmol/L (normal)

- Phosphate- 1.52mmol/L (normal)


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Daily urine dipstick

- To assess urinary protein or any possible glycosuria

- Results:

- Daily showed 4+ proteinuria

24 hours urine protein

- 2.78g/L/24 hours ( increased )


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Urine FEME and culture

- To rule out urinary tract infection, red cells and red cell

cast.

- Culture- no growth

- Pus cell- nil

- Red blood cell- nil

- Epithelial cell- 2

- Normal results not suggestive of glomerulonephritis


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Erythrocyte Sedimentation Rate -To help in diagnosis infection, inflammation

or malignancy such as TB, RA, connective

tissue disease.- Better as monitoring the inflammatory or

- malignancy

- Result:

- ESR-114mm/Hr- increase as normal within10mm/Hr


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Coagulation Test:- To assess hypercoagulable states a

complication in nephrotic syndrome

Results:

Prothrombin Time- 14.1s( increase)INR- 1.08 (normal)

APTT- 41.3s (increase)

- There was presence of hypercoagulable state

- It may due to liver disease however the plaletetcount and liver function test was normal


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Cardiac Enzyme and ECG

- To see any possible underlying cardiac problem that

cause edematous

- Results:

CK- 65 U/mL, normal

LDH- 240U/L, normal

-Normal ECG


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Lipid Profile:

- Possible of hyperlipidemia in nephrotic syndrome

- May associated with underlying cardiac disease

- Results:

- Triglyceride-7.05mmol/L (increase)

- Cholesterol- 19.28 mmol/L (increase)

- LDL-281IU/L (increase)

- HDL- 0.48 mmmol/L (decrease)


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- Fasting blood glucose- 4.1mmol/LIt is for detecting diabetes mellitus that causenephropathy

- Screen for HIV (Retrovirus)-

- Hepatitis B and C- negative- ANA( antinuclear antibody)- any SLE

- Rheumatoid Factor- Inflammatory disease

- Complement C3 and C4-may decrease in immune

complex-mediated glomerulonephritis- Antistreptolysin titer may show evidence of

streptococcus infection- negative


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Renal Biopsy (plan for next week)- Histological diagnosis as to see whether the it

will be responding to steroid such as inminimal changes glomerulonephritis

Ultrasound for Kidney, ureter and bladder(KUB)

- Good as no radiation and contrast medium are

used- To assess pelvicalyceal dilatation for anyobstruction, any polycystic kidney, renal mass,intrarenal and perinephritic fluids.

Management


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Management

General measures:- Monitor daily Blood pressure, Pulse rate, Temperatureand Respiratory rate to detect any infection ordehydration

- Nephrotic Chart ( consist of daily BP, Weight, Urine

albumin, Intake and output )- Input and Output chart to assess his fluid loss andbalance

- Fluids restriction with 800cc daily to decreaseedematous

- Diet with sodium restriction- Frusemide IV 20mg BD for diuresis


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- Prophylaxis heparin 5000 unit BD as in nephroticdue to increase fibrinogen synthesis from liver and

loss of antithrombin in urine will cause

hypercoaguable state

- Atovastatin (HMG- COA reductase inhibitor)due to hyperlipidemia that will increase risk of

myocardial disease and peripheral vascular

disease

- If any infection, antibiotic should be given- If any oliguria or defect in renal function

test,albumin, mannitol or other diuretic should be

given


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NEPHROTIC SYNDROME

Definition


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Definition

A collection of signs and symptomsA condition characterized by

massive edema

heavy proteinuria(>40mg/m2 in children,>3.5g in adult )

Hypoalbuminemia(


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treatment of idiopathic NS:

Congenital NS :

- NS presenting within the first 3 months

of life

Infantile NS:

-NS presenting between 3 and 12

months of life


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Frequent relapse

- 2 or more relapses within 6 months of

initial response or 4 or more relapses

within any 12 months periods

Steroid dependence

- 2 consecutive relapses during steroid

treatment or within 14 days after itscessation


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Steroid sensitive NS

- normalization of proteinuria within 4

weeks after start of standard initial

therapy with daily, oral prednisolone

Steroid resistant

- failure to achieve remission in spite of 4

weeks of prednisolone 60mg/ m2/ day

Pathophysiology


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Pathophysiology

Proteinuria

Structural damage to the glomerular basement membrane

Increase in size and number of pores

Allowing passage of more and larger molecules

PROTEINURIA

Reduction of negatively charge components present in glomerular

capillary wall which repel negatively charged protein molecules


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Pathogenesis of oedema in hypoalbuminaemia

A reduction in the concentration of osmotically activealbumin molecules in the blood

Reduction in the oncotic force that retains fluid within

blood vessels

Salt and water escape into the extravascularcompartment

OEDEMA


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Causes of nephrotic syndrome


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Causes of nephrotic syndrome

Primary glomerular diseaseAll types of glomerulonephritis

Membranous disease is the most common

form to cause nephrotic syndrome in adult

Minimal change glomerular disease

accounts for most cases in childhood

Glomerulopathy


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Secondary glomerular disease1. Systemic disease

Henoch-Schonlein purpura

Vasculitis (e.g. SLE)

Infections (e.g. malaria )

Allergen (e.g. bee sting) Diabetic glomerular disease

2. Drugs

Penicillamine, high dose captopril

Combines with a plasma protein to form an antigenic hapten, induces animmune complex mediated glomerulonephritis

3. Toxins


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Clinical signs of nephrotic syndrome periorbital oedema (particularly on waking), the

earliest sign

scrotal, leg and ankle edema

ascites

SOB due to pleural effusions and abdominal

distention

* neither elevation of JVP nor pulmonaryoedema are features of nephrotic syndrome

Pattern of disease


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Pattern of diseaseChildren Adults

Usually primaryglom

disease

Minimal change GN

Usually secondary

Membranous GNTreatment: usually start

steroid without doing

renal biopsy (80% of

children response to

prednisolone)

Treatment : Treat

underlying cause

Usually recover Progressive course

Steroid-sensitive

h ti d


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nephrotic syndrome

Over 90% of children with nephrotic syndrome Proteinuria resolves with corticosteroid therapy

Commoner in boys and inatopic families

Often precipitatedby respiratory infections

Features suggesting: Age between 1 and 10 years

No macroscopic hamaturia

Normal blood pressure

Normal complement levels

Normal renal function


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Renal histology is usually normal on light microscopy butpodocyte fusion is seen on electron microscopy minimal

change disease

Protein leak is mainly of low-molecular weight protein

selective proteinuria Do not progress to renal failure

Prognosis 1/3resolve directly

1/3infrequent relapse

1/3frequent relapses; steroid dependent

Steroid-resistant


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nephrotic syndrome

Managed by paediatric nephrologist

Management of oedema

Diuetic therapy

Salt restriction

Captopril (ACE inhibitor)


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Cause Specific Features Prognosis

Focal Segmental

Glomerulosclerosis

Most common

Familial or idiopathic

30% progress to ESRF in 5

years; 20% response to

cyclophosphamide,

vincristine or cyclosporin

Membranous nephropathy Associated with hepatitis B Most remit spontaneously

within 5 years

May precede SLE

Mesangiocapillary

Glomerulonephritis

(membranoproliferative

glomerulonephritis

More common in older

children

Hematuria & low

complement level present

Decline in renal function

over many years


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Complication


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p

hypovolemia a low urinary sodium ( < 20 mmol/L) and a high

packed cell volume are indications ofhypovolemia

during the initial phase of oedema formation the

intravascular compartment may become volume-depleted

complainsof abdominal pain and feel faint

peripheral vasoconstriction and urinaty sodiumretention

urgent treatment with IV albumin (4.5%) aschild at risk of vascular thrombosis andshock

venous thrombosis

hypovolemia


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hypovolemia

Sluggish blood flow

Predispose to venous thrombosis

Hypercoagulable state

Loss of clotting factor (e.g. antithrombin)

Increaase hepatic production of fibrinogen

Increase blood viscosity from the raised hematocrit

prolong bed rest should be avoided

once renal vein thrombosis had occurred, prolonganticoagulation is required


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Sepsis Important cause of death in nephrotic

syndrome

Increase susceptibility to infection is due toloss of immunoglobulin in the urine

Pneumococcal infections are particularlycommon and pneumococcal vaccineshould be given

Penicillin prophylaxis should be given toall children while they havehypoalbuminaemia


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oliguric renal failure a low blood volume and hypotension may

lead to underperfused kidneys

acute tubular necrosis may rapidlydeveloped when renal ischemia occurs

from other complications such as blood

loss or septicaemia

albumin infusion combined with mannitol

or another diuretic may initiate a diuresis


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Lipid abnormalities Increased hepatic albumin synthesis is

accompanied by increased cholesterolsynthesis

Hypertriglyceridaemia present in about50% of patients

increase risk of MI or peripheral vasculardisease

best treated with HMG-CoA reductaseinhibitor

Modified ISKDC Regime


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g

Scheme of treatment of idiopathic NS


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16.Nephrotic Syndrome

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