Nephrotic Syndrome..

(NS)

Prepared by:Mohammad Ali Al-shehri .. Supervised by : Dr.

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. (4-increase, 1-decrease).

Nephrotic Criteria:*Massive proteinuria: qualitative proteinuria: 3+ or 4+, quantitative proteinuria : more than 40 mg/m2/hr in children (selective).

*Hypo-proteinemia : total plasma proteins < 5.5g/dl and serum albumin : < 2.5g/dl.

*Hyperlipidemia: serum cholesterol : > 5.7mmol/L

*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:
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 NS in child. mainly discussed.
B-Secondary NS:

NS resulted from systemic diseases, such as anaphylactoid purpura , systemic lupus erythematosus, HBV infection.
C-Congenital NS: rare

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

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

Heroin, gold, NSAID, captopril, probenecid, volatile hydrocarbons Infection: APSGN, HBV, HIV, shunt nephropathy, reflux nephropathy, leprosy, syphilis, Schistosomiasis, hydatid disease
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 syn, 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 Light microscopy, and Under Immunofluorescence *under Electron microscopy fusion of the foot processes of the podocytes
(2) NonMCN 20% *Mesangial proliferative glomerulonephritis

(MsPGN): about 10%

*Focal segmental glomerulosclerosis (FSGS): 5% *Membranous Nephropathy (MN) : 2% *Membrane proliferative glomerulonephritis

(MPGN) : 1%

*Others rare,Cresent glomerulonephritis

 NB: *Nephrotic syndrome is 15 times more common in

children than in adults.

*Most cases of primary nephrotic syndrome are in

children and are due to minimal-change disease. The age at onset varies with the type of nephrotic syndrome.

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 0.5g/m2/day

Moderate 0.5 2g/m2/day Sever more than 2g/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.

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: *Reduction plasma colloid osmotic pressure

secondary to hypoalbuminemia Edema and hypovolemia

*Intravascular volume antidiuretic hormone (ADH

) and aldosterone(ALD) water and sodium retention Edema

*Intravascular volume glomerular filtration rate

(GFR) water and sodium retention Edema

How many pathological types causes nephrotic syndrome?

Clinical Manifestation:IN MCNS , The male preponderance of 2:1 : 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 penis and scrotum.

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 for children

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 5.7mmol/L (220mg/dl).

C-- ESR100mm/hr during activity phase . 3.Serum complemen: Vary with clinical type.

4.Renal function

Kidney Biopsy:-

Considered in:

1-Secondary N.S 2-Frequent relapsing N.S 3-Steroid resistant N.S

4- Hematuria 5-Hypertension 6- Low GFR

Differential Diagnosis of NS:

D.D of generalized edema: 1-Protein losing enteropathy 2-Hepatic Failure. 3-HF 4-Protein energy malnutrition 5-Acute and chronic GN 6-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 urine. B-the edema fluid act as a culture medium. C-use immunosuppressive agents. D- malnutrition The common infection : URI, peritonitis, cellulitis and UTI may be seen. 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.

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

thrombosis: 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

3-ARF: pre-renal and renal

4-

cardiovascular disease :-Hyperlipidemia, may be a risk factor for cardiovascular disease.

5-Hypovolemic shock

6-Others: growth retardation, malnutrition, adrenal cortical insufficiency

Management of NS:
General (non-specific ) *Corticosteroid therapy

General therapy: Hospitalization:- for initial work-up and evaluation of

treatment.
Activity: usually no restriction , except Diet

massive edema,heavy hypertension and infection.

Hypertension and edema: Low salt diet (<2gNa/ day) only during period of edema or salt-free diet. Severe edema: Restricting fluid intake Avoiding infection: very important. Diuresis: Hydrochlorothiazide (HCT) 2mg/kg.d Antisterone 24mg/kg.d Dextran 1015ml/kg , after 3060m, followed by Furosemide (Lasix) at 2mg/kg .

Induction use of albumin:-

Albumin + Lasix (20 % salt poor)

1-Severe edema 2-Ascites 3-Pleural effusion 4-Genital edema 5-Low serum albumin

Corticosteroidprednisone therapy:-

Prednisone tablets at a dose of 60 mg/m2/day (maximum daily dose, 80 mg divided into 2-3 doses) for at least 4 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 nephrotic syndrome will experience at least 1 relapse (3-4+proteinuria plus edema). daily divided-dose prednisone at the doses noted earlier (where he has the relapse) until the child enters remission (urine trace or negative for protein for 3 consecutive days). The pred-nisone 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 5 consecutive days.

* Relapse: edema, or first morning urine sample contains > 2 + protein for 7 consecutive days. *Frequent relapsing: > 2 relapses within 6 months (> 4/year). *Steroid resistant: failure to achieve remission with prednisolone given daily for 28 days.

Side Effects With Long Term Use of Steroids Steroid toxicity

-Stunted growth Cataracts - Pseudotumor cerebri -Psycosis -Osteoporosis - Cushingoid features

hyperglycemia myopathy peptic ulcer poor healing of wound. Hirsutism Thromboembolism

-Adrenal gland suppression

Alternative agent: When can be used:

Steroid-dependent patients, frequent relapsers, and steroid-

resistant patients.

Cyclophosphamide Pulse steroids Cyclosporin A Tacrolimus Microphenolate

 THE END.

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