nephrotic syndrome h

Prepared by:-

Wahyu Tri Utomo

Definition of NSEtiology of NS

Pathology of NSPathophysiology of NS

Clinical Manifestation of NSComplication NS

Laboratory DataDiagnosisTreatment

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).

Abdel-Hafez M, et al. Idiopathic nephrotic syndrome and atopy: i Am J Kidney Dis. 2009

*Massive proteinuria: qualitative proteinuria: 2+, 3+ or 4+, quantitative proteinuria : more than 40 mg/m2/day in children (selective).

*Hypo-proteinemia : total plasma proteins < 5.5g/dl and serum albumin : 5.7mmol/L

*Edema: pitting edema in different degree


-Hematuria: RBC in urine (gross hematuria)

-Hypertension:130/90 mmHg in school-age children120/80 mmHg in preschool-age children110/70 mmHg in infant and toddlers children

-Azotemiarenal insufficiency: Increased level of serum BUN Cr-Hypo-complementemia: Decreased level of serum c3


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


Drug,Toxic,Allegy: mercury, snake venom, vaccine, pellicillamine, Heroin, gold, NSAID, captopril, probenecid, volatile hydrocarbonsInfection: APSGN, HBV, HIV, shunt nephropathy, reflux nephropathy, leprosy, syphilis, Schistosomiasis, hydatid disease

Autoimmune or collagen-vascular diseases: SLE, Hashimotos thyroiditis,, HSP, VasculitisMetabolic 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 nephrosclerosisAbdel-Hafez M, et al. Idiopathic nephrotic syndrome and atopy: i Am J Kidney Dis. 2009

Minimal Change Nephropathy (MCN):

NS:-*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.

Salsano ME, et al. Atopy in childhood idiopathic nephrotic syndrome. Acta Paediatr. 2007.

The Main Trigger Of primary Nephrotic Syndrome and Fundamental and highly important change of pathophysiology :-

Proteinuria


Increase glomerular permeability for proteins due to loss of negative charged glycoprotein

Degree of protineuria:-Mild less than 0.5g/m2/dayModerate 0.5 2g/m2/daySever 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 HMWB-Non selective :LMW+HMW are lost in urine


*Due to hyperproteinuria----- Loss of plasma protein in urine mainly the albumin. *Increased catabolism of protein during acute phase.Salsano ME, et al. Atopy in childhood idiopathic nephrotic syndrome. Acta Paediatr. 2007.

*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 lipoproteinSalsano ME, et al. Atopy in childhood idiopathic nephrotic syndrome. Acta Paediatr. 2007.

*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


IN MCNS , The male preponderance of 2:1

: 1.Main manifestations: Edema (varying degrees) is the common symptomLocal 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 lethargyloss of appetite, nausea and vomiting ,abdominal pain , diarrhea

body weight increase, urine output decrease pleural effusion (respiratory distress)


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 Lin CY, Lee BH, Lin CC, Chen WP. A study of the relationship between childhood nephrotic syndrome and allergic diseases

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

.

Considered in: 1-Secondary N.S

2-Frequent relapsing N.S

3-Steroid resistant N.S

4- Hematuria

5-Hypertension

6- Low GFR


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 edemaSalsano ME, et al. Atopy in childhood idiopathic nephrotic syndrome. Acta Paediatr. 2007.

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


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.


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 Salsano ME, et al. Atopy in childhood idiopathic nephrotic syndrome. Acta Paediatr. 2007.

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 insufficiencySalsano ME, et al. Atopy in childhood idiopathic nephrotic syndrome. Acta Paediatr. 2007.

General (non-specific )

*Corticosteroid therapy

Guideline for the Management of Nephrotic Syndrome; Renal Unit, Royal Hospital for Sick Children, Yorkhill Division, Oct 2007

Hospitalization:- for initial work-up and evaluation of treatment.

Activity: usually no restriction , except massive edema,heavy hypertension and infection.

Diet Hypertension and edema: Low salt diet (

Albumin + Lasix (20 % salt poor)

1-Severe edema2-Ascites3-Pleural effusion4-Genital edema5-Low serum albumin

Guideline for the Management of Nephrotic Syndrome; Renal Unit, Royal Hospital for Sick Children, Yorkhill Division, Oct 2007

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. Guideline for the Management of Nephrotic Syndrome; Renal Unit, Royal Hospital for Sick Children, Yorkhill Division, Oct 2007

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.

Guideline for the Management of Nephrotic Syndrome; Renal Unit, Royal Hospital for Sick Children, Yorkhill Division, Oct 2007.

*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.Guideline for the Management of Nephrotic Syndrome; Renal Unit, Royal Hospital for Sick Children, Yorkhill Division, Oct 2007

hyperglycemiamyopathypeptic ulcerpoor healing of wound.HirsutismThromboembolism -Stunted growth

Cataracts

- Pseudotumor cerebri

-Psycosis

-Osteoporosis

- Cushingoid features

-Adrenal gland suppression

Guideline for the Management of Nephrotic Syndrome; Renal Unit, Royal Hospital for Sick Children, Yorkhill Division, Oct 2007.

When can be used:

Steroid-dependent patients, frequent relapsers, and steroid-resistant patients.

Cyclophosphamide Pulse steroids

Cyclosporin A

Tacrolimus

MicrophenolateGuideline for the Management of Nephrotic Syndrome; Renal Unit, Royal Hospital for Sick Children, Yorkhill Division, Oct 2007

THE END.

THANK YOU.

Abdel-Hafez M, et al. Idiopathic nephrotic syndrome and atopy: is there a common link? Am J Kidney Dis. 2009Salsano ME, et al. Atopy in childhood idiopathic nephrotic syndrome. Acta Paediatr. 2007.Lin CY, Lee BH, Lin CC, Chen WP. A study of the relationship between childhood nephrotic syndrome and allergic diseases.Chest. 1990.Paediatric Protocols For Malaysian Hospitals (2nd Edition)http://emedicine.medscape.comSteroid dependent and steroid resistant nephrotic syndrome in children, treatment and outcomes at Tripoli Children Hospital - Dr. Naziha R. Rhuma, Dr. O. Fituri, Dr. A. Boaeshi, Dr. M. Turky, April 2006.Guideline for the Management of Nephrotic Syndrome; Renal Unit, Royal Hospital for Sick Children, Yorkhill Division, Oct 2007.

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nephrotic syndrome h

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