Nephrotic Syndrome..

(NS)

Loai Eid
MD, MSHS, FAAP, FASPN
28/04/2015

Nephrotic syndrome
Nephrotic syndrome (NS) results from increased
permeability of Glomeulrar basement membrane
(GBM) to plasma protein.

It is clinical and laboratory syndrome

characterized by massive proteinuria, which
lead to hypoproteinemia ( hypo-albuminemia),
hyperlipidemia and pitting edema.

Epidemiology
15 times commoner in children than in adults
Most cases of primary NS are in children and are due

to minimal-change disease (MCD). The age at onset

varies with the type of NS

Incidence of childhood NS in the USA is 1.5 : 100000

cases

Gender: M>F 2:1, 1:1 (adolescents)

Nephrotic Criteria
*Massive proteinuria:
qualitative proteinuria: 3+ or 4+,
quantitative proteinuria : more than 40 mg/m2/hr

*Hypo-proteinemia :
Total plasma proteins < 5.5 g/dl &
Serum albumin < 2.5 g/dl

*Hyperlipidemia:
Serum cholesterol : > 220 mg/dl

*Edema: pitting edema in different degree

Nephritic Criteria
-Hematuria: RBC in urine (gross hematuria)
-Hypertension:

130/90 mmHg in school-age children

120/80 mmHg in preschool-age children
110/70 mmHg in infant and toddlers children

-Azotemiarenal insufficiency:

Increased level of serum BUN Cr

-Hypo-complementemia:
Decreased level of serum c3

Classification
Based on aetiology :
Congenital or Acquired: Primary Or Secondary

Based on response to therapy:

Steroid sensitive/remission
Steroid dependent
Frequently relapsing
Steroid resistant - 25%

Classification
A-Primary Idiopathic NS (INS): majority

The cause is still unclear up to now. Recent 10 years

,increasing evidence has suggested that INS may result
from a primary disorder of T cell function.
Accounting for > 90 % of cases before 10 years
50 % after 10 years of age
B-Secondary NS:

NS resulted from systemic diseases, such as anaphylactoid

purpura , systemic lupus erythematosus, HBV infection.
C-Congenital NS: rare, gene mutations Vs nongenatic causes

*1st 3monthe of life ,only treatment renal transplantation

Secondary NS
Drug,Toxic,Allegy: mercury, snake venom, vaccine, pellicillamine,

Heroin, gold, NSAID, captopril, probenecid

Infection: APSGN, HBV, HIV, shunt nephropathy, reflux
nephropathy, leprosy, syphilis
Autoimmune or collagen-vascular diseases: SLE, Hashimotos
thyroiditis, HSP, Vasculitis
Metabolic disease: Diabetes mellitus
Neoplasma: Hodgkins disease, carcinoma ( renal cell, lung,
neuroblastoma, breast, and etc)
Genetic Disease: Alport syndrome, Sickle cell disease, Amyloidosis,
Congenital nephropathy
Others: Chronic transplant rejection, congenital nephrosclerosis

Idiopathic NS (INS): Pathology

Minimal Change Nephropathy (MCN): <80%

The glomeruli appear normal basically Under the LM

& IF
NonMCN 20%
Membranoproliferative glomerulonephritis (MPGN)
8%
Focal and segmental glomerulosclerosis (FSGS) 7%
Proliferative glomerulonephritis 2 %
Mesangial proliferation 2 %
Focal and global glomerulosclerosis 2 %
Membranous glomerulonephropathy 2 %

Minimal Change Disease

1-6 years of age
Absence of hypertension
Absence of hematuria
Normal complement levels
Normal renal function

Pathophysiology

The Main Trigger Of primary Nephrotic Syndrome

and Fundamental and highly important change of
pathophysiology :-

Proteinuria

Pathogenesis of Proteinuria
Increase glomerular permeability for proteins due to loss of

negative charged glycoprotein

Degree of protineuria: Mild less than 0.5 g/m2/day
Moderate 0.5 2 g/m2/day
Sever more than 2 g/m2/day
Type of proteinuria: A-Selective proteinuria: where proteins of low molecular

weight .such as albumin, are excreted more readily than

protein of HMW
B-Non selective :
LMW+HMW are lost in urine

Pathogenesis of Hypoalbuminemia

*Due to hyperproteinuria----- Loss of plasma

protein in urine mainly the albumin.
*Increased catabolism of protein during acute
phase.

How many pathological types causes

nephrotic syndrome?

Pathogenesis of Hyperlipidemia
*Response to Hypoalbuminemia reflex to liver --

synthesis of generalize protein ( including

lipoprotein ) and lipid in the liver ,the lipoprotein
high molecular weight no loss in urine
hyperlipidemia

*Diminished catabolism of lipoprotein

Pathogenesis of Edema
*Secondary to hypoalbuminemia plasma oncotic

pressure Edema and hypovolemia

*Intravascular volume antidiuretic hormone

(ADH ) and aldosterone water and sodium

retention Edema

*Intravascular volume glomerular filtration

rate (GFR) water and sodium retention

Edema

Clinical Manifestation
1.Main manifestations:
Edema (varying degrees) is the common symptom
Local edema: edema in face , around eyes ( Periorbital swelling) , in
lower extremities.
Generalized edema (anasarca), edema in genital area.

2-Non-specific symptoms:
Fatigue and lethargy
loss of appetite, nausea and vomiting , abdominal pain , diarrhea
body weight increase, urine output decrease
pleural effusion (respiratory distress)

Investigations
1-Urine analysis:

A-Proteinuria : 3-4 + SELECTIVE.

B-24 urine collection for protein
>40mg/m2/hr or Spot Urine protein/creatinine >2
Normal UP /UCr <0.2 mg/mg

C- volume: oliguria (during stage of edema formation)

D-Microscopically:
microscopic hematuria 20%, large number of hyaline cast

Investigations
2-Blood:
A-serum protein: decrease >5.5gm/dL , Albumin levels are

low 2.5gm/dL
B-Serum cholesterol and triglycerides:
Cholesterol 220mg/dl
C-ESR100mm/hr during activity phase , Blood culture
D-Serum complement Vary with clinical type( Normal)
E-Renal function
F-Labs for 2nd causes: ASO titer, ANA, HbsAg, HbC ..etc

3-CXR: plural effusion

4- Renal Ultrasound

Initial Therapy vs Biopsy

Older

than 1 year and less than 10 years of age

None of the following clinical findings are present:

hypertension, gross hematuria, and a marked

elevation in serum creatinine
Normal complement levels

Kidney Biopsy
Considered in:

1-Secondary N.S

2-Frequent relapsing N.S

3-Steroid resistant N.S

4-Hematuria, low complement

5-Hypertension
6- Atypical NS

Differential Diagnosis of NS

D.D of generalized edema:

1-Protein losing enteropathy
2-Hepatic Failure
3-HF
4-Acute and chronic GN
5-Urticaria? Angio edema

Complications of NS
1-Infections:Infections is a major complication in children with
NS. It frequently trigger relapses.
Nephrotic pt are liable to infection because :
A-Loss of Immunoglobins in the urine
B-The edema fluid act as a culture medium
C-Use immunosuppressive agents
D- malnutrition
The common infection : URI, peritonitis, cellulitis, pneumonia
and UTI
Organisms: encapsulated (Pneumococci, H.influenzae),
Gram negative (e.g E.coli)

Complication

Vaccines in NS:
- Polyvalent pneumococcal vaccine (if not previously
immunized) when the child is in remission and off daily
prednisone therapy
- Children with a negative varicella titer should be given
varicella vaccine when off steroid therapy
- Annual Flu vaccine

Complication..
2-Hypercoagulability (Thrombosis).
Hypercoagulability of the blood leading to venous or arterial

thrombosis (Albumin <2 g/dl)

Hypercoagulability in Nephrotic syndrome caused by:

1-Higher concentration of I,II, V,VII,VIII,X and fibrinogen

2- Lower level of anticoagulant substance: antithrombin III

3-Decrease fibrinolysis.

4-Higher blood viscosity

5- Increased platelet aggregation

6- Overaggressive diuresis

Complication..

3- ARF: pre-renal and renal (drug ATN, RVT)

4- Cardiovascular disease : Hyperlipidemia, may be a risk factor

for cardiovascular disease

5- Hypovolemic shock

6- Others: growth retardation, malnutrition,

adrenal cortical insufficiency

7- Bone disease: Loss of vitamin D binding protein in the urine

leading to hypovitaminosis and malabsorption of calcium.

Management of NS
General (non-specific ):
To treat underlying aetiology
To treat proteinuria
To treat oedema

To treat hypertension
To treat complications
Corticosteroid therapy

General Therapy
Hospitalization: for initial work-up and evaluation for Tx
Activity: usually no restriction , except massive edema,

hypertension and infection.

Diet:

Hypertension and edema: Low salt diet (<2 gNa/day) only

during period of edema or salt-free diet
Severe edema: Restricting fluid intake
Avoiding infection: very important
Diuresis: Furosemide (Lasix) 1 mg/kg

Induction use of albumin

Albumin 25% ( 1g/kg) + Lasix (20 % salt poor):

1-Severe edema & Ascites

2-Pleural effusion
3-Genital edema
4-Low serum albumin < 1 g/dl
No Live vaccines while on steroids
Gastro-protection: Zantac

Corticosteroidprednisone therapy

Prednisone at a dose of 60 mg/m2/day (maximum daily

dose, 80 mg divided into 1-2 doses) for at least 4-6
consecutive weeks.
After complete absence of proteinuria, prednisone dose
should be tapered to 40 mg/m2/day given every other
day as a single morning dose.
The alternate-day dose is then slowly tapered and
discontinued over the next 2-3 mo.

Treatment of relapse in NS
Many children with NS will experience at least 1 relapse
(3-4+proteinuria plus edema).
Retreat with daily prednisone at the same doses 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 and tapered over 1-2 mo.

According to response to prednisone therapy

*Remission: no edema, urine is protein free for 3 consecutive
days and albumin> 3.5 g/dl (complete).
* Relapse: edema, or first morning urine sample contains > 2 +
protein for 3 consecutive days.
*Frequent relapsing: > 2 relapses within 6 months (> 4/year).
Steroid dependent: 2 consecutive relapses during period of
steroid taper or within 14 days of its cessation
*Steroid resistant: Failure to achieve Remission within 4 weeks
of full dose steroids

Long Term Use of Steroids Steroid toxicity

- Stunted growth
- Cataracts

hyperglycemia
myopathy
peptic ulcer

- Pseudotumor cerebri

poor healing of wound

- Psycosis

Hirsutism

- Osteoporosis

Thromboembolism

- Cushingoid features

- Adrenal gland suppression

Alternative agent
When can be used:
Steroid-dependent patients, frequent relapsers, and steroid-

resistant patients.

Cyclophosphamide + steroids

Cyclosporin A

Tacrolimus

Cellcept

Prognosis
10 year survival: >90%

Rarely progress to CRF

The primary glomerular lesion
Type and degree of renal damage
Age
Response to therapy
Treatable causes of nephrotic syndrome such as drug, toxins,

infections

Nursing Process: The Child With NS

Excess Fluid Volume related to fluid

accumulation in tissues and third spaces

Risk for Imbalanced Nutrition: Less than
Body Requirements related to anorexia
Risk for Impaired Skin Integrity related to
edema
Fatigue related to edema and disease process
Risk for Infection related to immunosuppression
Deficient Caregiver Knowledge related to
disease process, treatment, and home care

Nursing Management: Initial Assessment

Height, weight, Fluid balance
Vital Signs: Temperature and Pulse
Volume status
Perfusion
Capillary refill
Bp
Urinary output

Nursing Management: Parent teaching

All families should receive written information on NS
Children with steroid sensitive NS should have their

urine tested for proeteinuria daily at home using

Albustix
All families should have a management plan in case
of relapse and details of who to contact should they
have concern
Website for hand outs for patients:
http://KidneyWeb.net

Nursing Management: Diet

Salt intake and fluid restriction
Limit calorie intake on steroids
Normal protein intake
healthy diet for all the family

Discharge management plan

Nephrotic Syndrome Discharge Planning Checklist

Date complete

Nephrotic syndrome info sheet/website links

Renal Medication Information Booklet

Prednisolone dose and reducing regimen
Steroid prescription
Omeprazole/Ranitidine regimen

Urinalysis
Parent/carer education complete
Diary record
Albustix provided

Dietetic referral
Diet information sheet
Fluid restriction during relapse discussed

Infection
Pneumococcal vaccination confirmed/arranged
Varicella status:
positive
negative
Advice given for VZ seronegative

Follow up
Out patient appointment issued
Contact number/details issued

 THE END.

THANK YOU.