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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.
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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 toddler’s children -Azotemia(renal 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, Hashimoto’s thyroiditis,, HSP, Vasculitis • Metabolic disease: Diabetes mellitus • Neoplasma: Hodgkin’s 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) Non—MCN: <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
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-- ESR↑>100mm/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 • massive edema,heavy hypertension and infection. • Diet 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 : 2~4mg/kg.d • Dextran : 10~15ml/kg , after 30~60m, • 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
Corticosteroid—prednisone 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.
hyperglycemia myopathy peptic ulcer poor healing of wound. Hirsutism Thromboembolism Side Effects With Long Term Use of Steroids“Steroid toxicity • -Stunted growth • Cataracts • - Pseudotumor cerebri • -Psycosis • -Osteoporosis • - Cushingoid features • -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
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